PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 11829203-1 2001 INTRODUCTION: The polymorphic cytochrome P450 enzyme 2C9 (CYP2C9) catalyses the metabolism of many drugs including S-warfarin, acenocoumarol, phenytoin, tolbutamide, losartan and most of the non-steroidal anti-inflammatory drugs. Losartan 166-174 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 30-56 11829203-1 2001 INTRODUCTION: The polymorphic cytochrome P450 enzyme 2C9 (CYP2C9) catalyses the metabolism of many drugs including S-warfarin, acenocoumarol, phenytoin, tolbutamide, losartan and most of the non-steroidal anti-inflammatory drugs. Losartan 166-174 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 58-64 11408373-0 2001 Role of CYP2C9 polymorphism in losartan oxidation. Losartan 31-39 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 8-14 11408373-6 2001 In comparison to the CYP2C9.1 variant, oxidation of losartan was significantly reduced in yeast expressing the rare CYP2C9.2 or CYP2C9.3 variants. Losartan 52-60 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 116-122 11408373-7 2001 Moreover, the rate of losartan oxidation was lower in liver microsomes from individuals hetero- or homozygous for the CYP2C9*3 allele, or homozygous for the CYP2C9*2 allele. Losartan 22-30 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 118-124 11408373-7 2001 Moreover, the rate of losartan oxidation was lower in liver microsomes from individuals hetero- or homozygous for the CYP2C9*3 allele, or homozygous for the CYP2C9*2 allele. Losartan 22-30 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 157-163 11408373-9 2001 In summary, these in vitro results indicate that CYP2C9 is the major human P450 isoenzyme responsible for losartan oxidation and that the CYP2C9 genotype contributes to interindividual differences in losartan oxidation and activation. Losartan 106-114 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 49-55 11408373-9 2001 In summary, these in vitro results indicate that CYP2C9 is the major human P450 isoenzyme responsible for losartan oxidation and that the CYP2C9 genotype contributes to interindividual differences in losartan oxidation and activation. Losartan 200-208 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 49-55 11408373-9 2001 In summary, these in vitro results indicate that CYP2C9 is the major human P450 isoenzyme responsible for losartan oxidation and that the CYP2C9 genotype contributes to interindividual differences in losartan oxidation and activation. Losartan 200-208 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 138-144 11408373-2 2001 The aim of the present investigation was to study the contribution of CYP2C9 and CYP3A4 in losartan oxidation in vitro and to evaluate the role of CYP2C9 polymorphism. Losartan 91-99 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 70-76 11408373-6 2001 In comparison to the CYP2C9.1 variant, oxidation of losartan was significantly reduced in yeast expressing the rare CYP2C9.2 or CYP2C9.3 variants. Losartan 52-60 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 21-27 11408373-6 2001 In comparison to the CYP2C9.1 variant, oxidation of losartan was significantly reduced in yeast expressing the rare CYP2C9.2 or CYP2C9.3 variants. Losartan 52-60 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 116-122 10678291-4 2000 Losartan is distinguished from other ARBs by cytochrome P450 (CYP) 3A4- and CYP2C9-mediated biotransformation to its active metabolite EXP-3174. Losartan 0-8 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 76-82 11368292-15 2001 The oral clearances of the CYP2C9 substrates diclofenac, tolbutamide, glibenclamide (glyburide) and losartan are reduced by 15 to 25% when coadministered with fluvastatin. Losartan 100-108 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 27-33 10877007-5 2000 Losartan and irbesartan inhibited the CYP2C9-associated tolbutamide methylhydroxylation more potently (Ki values 4.1 microM and 24.5 microM), than valsartan, candesartan or eprosartan (Ki values 135 microM, 155 microM and > 1000 microM, respectively). Losartan 0-8 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 38-44 10197301-1 1999 Losartan is an angiotensin II receptor antagonist that is metabolized by CYP2C9 and CYP3A4 to a more potent antihypertensive metabolite, E3174. Losartan 0-8 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 73-79 10562462-1 1999 CYP2C9 catalyzes the metabolism of important drugs such as phenytoin, S-warfarin, tolbutamide, losartan, and nonsteroidal anti-inflammatory drugs. Losartan 95-103 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 0-6 9920790-1 1999 Cytochrome P450 2C9 (CYP2C9) catalysis the metabolism of important drugs such as phenytoin, S-warfarin, tolbutamide, losartan, torasemide, and nonsteroidal anti-inflammatory drugs. Losartan 117-125 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 0-19 9920790-1 1999 Cytochrome P450 2C9 (CYP2C9) catalysis the metabolism of important drugs such as phenytoin, S-warfarin, tolbutamide, losartan, torasemide, and nonsteroidal anti-inflammatory drugs. Losartan 117-125 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 21-27 10197301-8 1999 Inhibition of losartan metabolism appears to require both CYP2C9 and CYP3A4 inhibition. Losartan 14-22 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 58-64 9542475-1 1998 BACKGROUND: Losartan is metabolized by CYP2C9 and CYP3A4 to an active metabolite, E3174, which has greater antihypertensive activity than the parent compound. Losartan 12-20 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 39-45 9542475-13 1998 Further studies are needed to define the contribution of other isozymes, particularly CYP2C9, to the pharmacokinetics of losartan and E3174. Losartan 121-129 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 86-92 9551703-1 1998 OBJECTIVE: Losartan is metabolised to its active metabolite E-3174 by CYP2C9 and CYP3A4 in vitro. Losartan 11-19 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 70-76 9551703-13 1998 This implicates that, in man, CYP2C9 is a major enzyme for the formation of E-3174 from losartan. Losartan 88-96 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 30-36 7736913-9 1995 It was then demonstrated that microsomes containing either recombinant human liver CYP2C9 or CYP3A4 were capable of oxidizing both losartan and the aldehyde E3179 to the carboxylic acid E3174. Losartan 131-139 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 83-89 7736913-10 1995 Subsequently, it was shown that rabbit anti-CYP2C9 and anti-CYP3A3/4 inhibited the oxidation of losartan to E3174 in incubations with human liver microsomes. Losartan 96-104 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 44-50 34638547-5 2021 The X-ray crystal structure of CYP2C9*8, which represents an amino acid variation from arginine to histidine at position 150 (R150H), was solved in complex with losartan. Losartan 161-169 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 31-37 34498315-2 2021 METHODS: A MassARRAY approach was used to detect single nucleotide polymorphism (SNP) loci in the URAT1 and CYP2C9 genes (16 and 2 loci, respectively) in 111 patients with hypertension and hyperuricemia taking losartan and in 121 healthy controls. Losartan 210-218 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 108-114 34638547-6 2021 The overall conformation of the CYP2C9*8-losartan complex was similar to the previously solved complex with wild type (WT) protein, but it differs in the occupancy of losartan. Losartan 167-175 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 32-38 34638547-10 2021 Interestingly, the CYP2C9*8 interaction with losartan was not as weak as the CYP2C9*3 variant, which showed up to three-fold weaker average dissociation constant compared to the WT. Losartan 45-53 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 19-25 34638547-11 2021 Taken together, the structural and solution characterization yields insights into the similarities and differences of losartan binding to CYP2C9 variants and provides a useful framework for probing the role of amino acid substitution and substrate dependent activity. Losartan 118-126 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 138-144 34210056-0 2021 Influence of CYP2C9 Genetic Polymorphisms on the Pharmacokinetics of Losartan and Its Active Metabolite E-3174: A Systematic Review and Meta-Analysis. Losartan 69-77 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 13-19 34210056-1 2021 This study aimed to investigate the influence of CYP2C9 genetic polymorphisms on the pharmacokinetics of losartan and its active metabolite, E-3174, through a systematic review and meta-analysis. Losartan 105-113 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 49-55 34210056-5 2021 We found that healthy volunteers with CYP2C9*2 or *3 carriers had higher area under the curve (AUC0- ) of losartan (mean difference (MD) 0.17 mug h/mL; 95% confidence intervals (CI): 0.04, 0.29) and lower AUC0- of E-3174 (MD -0.35 mug h/mL; 95% CI: -0.62, -0.08) than those with CYP2C9*1/*1. Losartan 106-114 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 38-44 34210056-7 2021 For half-life, subjects with CYP2C9*2 or *3 carriers had longer half-lives of losartan and E-3174 than those with CYP2C9*1/*1 (MD 0.47 h; 95% CI: 0.32, 0.61 and MD 0.68 h; 95% CI: 0.44, 0.92, respectively). Losartan 78-86 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 29-35 34210056-8 2021 This meta-analysis suggests that the pharmacokinetics of losartan and E-3174 are associated with the CYP2C9 polymorphisms. Losartan 57-65 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 101-107 35061161-2 2022 The herbal hepatoprotective medicine, silybin A inhibits cytochrome P450 (CYP) 2C9 and 3A4 enzymes, thus, may interact with the drugs that are substrates of CYP2C9 and 3A4, such as losartan. Losartan 181-189 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 57-90 35061161-2 2022 The herbal hepatoprotective medicine, silybin A inhibits cytochrome P450 (CYP) 2C9 and 3A4 enzymes, thus, may interact with the drugs that are substrates of CYP2C9 and 3A4, such as losartan. Losartan 181-189 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 157-163 35061161-4 2022 This study aimed to assess silybin A-losartan interaction in different CYP2C9 genotypes using physiological-based pharmacokinetic (PBPK) model approach. Losartan 37-45 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 71-77 35061161-10 2022 In CYP 2C9*1/*1 genotype, AUC and Cmax of losartan were increased 1.16 and 1.37 folds, respectively falling in a range stipulated for negligible interaction. Losartan 42-50 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 3-10 35061161-11 2022 Increase in AUC and Cmax by 0.873 and 0.294 folds, respectively in CYP2C9*1/*3 after co-administration of silybin A exhibited a minor interaction with losartan. Losartan 151-159 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 67-73 35061161-12 2022 However, in individuals with CYP2C9*1/*2 genotype, the losartan"s AUC and Cmax were decreased by 0.01 folds, manifesting a moderate interaction. Losartan 55-63 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 29-35 35061161-13 2022 Hence, in CYP2C9*1/*1 and CYP2C9*1/*3 genotypes, silybin A is a weak CYP inhibitor for losartan while in CYP2C9*1/*2 genotype, the co-administration of silybin consequents into a moderate pharmacokinetic interaction with losartan. Losartan 87-95 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 26-32 33556367-8 2021 In contrast, the binding of both SOR and SNO to active site residues in the closely related human CYP2C9 enzyme was similar, as were the IC50s determined against CYP2C9-mediated losartan oxidation. Losartan 178-186 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 162-168 35342886-8 2022 CYP2C9-reduced metabolism genotypes were associated with losartan response and uncontrolled hypertension (odds ratio (OR), 5.2; 95% CI, 1.9 to 14.7). Losartan 57-65 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 0-6 33509019-0 2021 Effect of CYP2C9 genetic polymorphism and breviscapine on losartan pharmacokinetics in healthy subjects. Losartan 58-66 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 10-16 33509019-9 2021 The activity of CYP2C9 enzyme to losartan metabolism was more significant in subjects with CYP2C9*1/*3 than those with CYP2C9*1/*1 genotype. Losartan 33-41 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 16-22 33509019-9 2021 The activity of CYP2C9 enzyme to losartan metabolism was more significant in subjects with CYP2C9*1/*3 than those with CYP2C9*1/*1 genotype. Losartan 33-41 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 91-97 33509019-9 2021 The activity of CYP2C9 enzyme to losartan metabolism was more significant in subjects with CYP2C9*1/*3 than those with CYP2C9*1/*1 genotype. Losartan 33-41 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 91-97 28972767-3 2017 Here we report the crystal structures of human CYP2C9 and its polymorphic variants, *3 (I359L) and *30 (A477T), with an antihypertensive drug losartan. Losartan 142-150 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 47-53 32272615-4 2020 Additionally, it strongly inhibited other CYP2C9-catalyzed diclofenac 4"-hydroxylation and losartan oxidation activities. Losartan 91-99 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 42-48 32186616-2 2019 Its dosage is related to the genetic characteristics of CYP2C9 enzymatic activity, which metabolizes losartan to its active form E-3174, responsible for the antihypertensive effect. Losartan 101-109 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 56-62 32186616-10 2019 A non-significant tendency to need a larger dose of losartan was observed with the CYP2C9 * 3 allele, with an odds ratio (OR) of 1.46 (95% confidence intervals (CI) 0.01-18.64). Losartan 52-60 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 83-89 32186616-13 2019 The presence of CYP2C9*3 is associated with the need for higher doses of losartan, possibly due to a decrease in the conversion of losartan to E-3174. Losartan 73-81 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 16-22 32186616-13 2019 The presence of CYP2C9*3 is associated with the need for higher doses of losartan, possibly due to a decrease in the conversion of losartan to E-3174. Losartan 131-139 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 16-22 29746595-2 2018 The allelic variant CYP2C9*30 (A477T) is associated to diminished response to the antihypertensive effects of the prodrug losartan and affected metabolism of other drugs. Losartan 122-130 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 20-26 32938720-0 2020 Structure of Cytochrome P450 2C9*2 in Complex with Losartan: Insights into the Effect of Genetic Polymorphism. Losartan 51-59 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 13-32 32938720-4 2020 The crystal structure of CYP2C9*2 in complex with an antihypertensive drug losartan was solved using X-ray crystallography at 3.1-A resolution. Losartan 75-83 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 25-31 32938720-5 2020 The Arg144Cys variation in the *2 complex disrupts the hydrogen-bonding interactions that were observed between the side chain of arginine and neighboring residues in the losartan complex of CYP2C9 and the wild-type (WT) ligand-free structure. Losartan 171-179 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 191-197 32938720-7 2020 The new structure revealed distinct interactions of losartan in the compact active site of CYP2C9*2 and differed in occupancy at the other binding sites previously identified in the WT-losartan complex. Losartan 52-60 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 91-97 32938720-8 2020 Furthermore, the binding studies in solution using losartan illustrated lower activity of the CYP2C9*2 compared with the WT. Losartan 51-59 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 94-100 32938720-9 2020 Together, the findings yield valuable insights into the decreased hydroxylation activity of losartan in patients carrying CYP2C9*2 allele and provide a useful framework to investigate the effect of a single-nucleotide polymorphism that leads to altered metabolism of diverse drug substrates. Losartan 92-100 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 122-128 32586526-0 2020 Variants in ADRB1 and CYP2C9: Association with Response to Atenolol and Losartan in Marfan Syndrome. Losartan 72-80 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 22-28 31058419-2 2019 Amlodipine is mainly metabolized by cytochrome P450 (CYP) 3A4, whereas losartan is metabolized by CYP2C9 and CYP3A4. Losartan 71-79 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 98-104 30472588-14 2019 CONCLUSIONS: This study advocates the use of a cocktail of bupropion, losartan and dapsone for in vivo phenotyping of CYP2B6, CYP2C9 and NAT2, which is important in determining therapeutic dose levels of anti-HIV and anti-TB drugs in HIV/AIDS-TB coinfections. Losartan 70-78 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 126-132 27934636-6 2017 In addition, these RAF values were applied to losartan and meloxicam, whose metabolism is mostly CYP2C9 mediated. Losartan 46-54 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 97-103 28805981-4 2017 Human CYP2C9 (wild type) isolated from a baculovirus-infected cell system was incubated with 0.8 mumol/L losartan for 20 min. Losartan 105-113 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 6-12 28805981-7 2017 Formation of the CYP2C9-produced losartan metabolite EXP-3174 was determined by validated LC-MS/MS methodology. Losartan 33-41 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 17-23 27934636-7 2017 Only using the RAF derived from testosterone for CYP3A4 produced the expected CYP2C9 contribution of 72%-87% and 47%-69% for metabolism of losartan and meloxicam, respectively. Losartan 139-147 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 78-84 27474842-3 2016 The aim of this study is to describe the distribution of CYP2C9*2, CYP2C9*3, CYP3A4*22 and CYP3A5*3 defective alleles, according to losartan tolerance in paediatric Marfan patients. Losartan 132-140 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 57-63 27474842-3 2016 The aim of this study is to describe the distribution of CYP2C9*2, CYP2C9*3, CYP3A4*22 and CYP3A5*3 defective alleles, according to losartan tolerance in paediatric Marfan patients. Losartan 132-140 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 67-73 26233334-6 2015 Phenotyping of CYP2C9 was performed by administration of a 50-mg single oral dose of losartan and by calculating the urinary metabolic ratio (MR) of probe drug to its metabolite E-3174. Losartan 85-93 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 15-21 27216792-6 2016 RESULTS: Based on the literatures published, it has been demonstrated that pharmacokinetic interactions of losartan with other agents are mainly via CYP2C9- and CYP3A4-mediated, the role played by CYP enzyme system in the metabolism of valsartan, candesartan, irbesartan, and azilsartan appears modest, and cytochrome P450 system has no influence on the metabolism of telmisartan, eprosartan, olmesartan. Losartan 107-115 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 149-155 27287328-5 2016 RESULTS: The results showed that apigenin has the inhibitory effect on the metabolism of losartan in vitro, the IC50 was 7.61, 4.10 and 11.07 mumol/l on recombinant CYP2C9 microsomes, human liver microsomes and rat liver microsomes, respectively. Losartan 89-97 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 165-171 26669712-6 2015 The CYP2C9 phenotype was determined using a single oral dose of 50 mg losartan. Losartan 70-78 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 4-10 26669712-8 2015 The urinary losartan to its metabolite E-3174 metabolic ratio (MR) was used as an index of CYP2C9 metabolic activity. Losartan 12-20 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 91-97 26551762-0 2016 The Role of CYP2C8 and CYP2C9 Genotypes in Losartan-Dependent Inhibition of Paclitaxel Metabolism in Human Liver Microsomes. Losartan 43-51 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 23-29 26551762-1 2016 The aim of the present study was to further investigate a previously identified metabolic interaction between losartan and paclitaxel, which is one of the marker substrates of CYP2C8, by using human liver microsomes (HLMs) from donors with different CYP2C8 and CYP2C9 genotypes. Losartan 110-118 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 261-267 26551762-2 2016 Although CYP2C8 and CYP2C9 exhibit genetic linkage, previous studies have yet to determine whether losartan or its active metabolite, EXP-3174 which is specifically generated by CYP2C9, is responsible for CYP2C8 inhibition. Losartan 99-107 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 178-184 26551762-6 2016 HLMs with either CYP2C9*2/*2 or CYP2C9*1/*3 exhibited a lower losartan intrinsic clearance (Vmax /Km ) than other HLMs including those with CYP2C9*1/*1 and CYP2C9*1/*2. Losartan 62-70 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 17-23 26551762-6 2016 HLMs with either CYP2C9*2/*2 or CYP2C9*1/*3 exhibited a lower losartan intrinsic clearance (Vmax /Km ) than other HLMs including those with CYP2C9*1/*1 and CYP2C9*1/*2. Losartan 62-70 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 32-38 26551762-6 2016 HLMs with either CYP2C9*2/*2 or CYP2C9*1/*3 exhibited a lower losartan intrinsic clearance (Vmax /Km ) than other HLMs including those with CYP2C9*1/*1 and CYP2C9*1/*2. Losartan 62-70 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 32-38 26551762-6 2016 HLMs with either CYP2C9*2/*2 or CYP2C9*1/*3 exhibited a lower losartan intrinsic clearance (Vmax /Km ) than other HLMs including those with CYP2C9*1/*1 and CYP2C9*1/*2. Losartan 62-70 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 32-38 26806573-0 2016 Effects of salvianolic acid B and tanshinone IIA on the pharmacokinetics of losartan in rats by regulating the activities and expression of CYP3A4 and CYP2C9. Losartan 76-84 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 151-157 25075423-5 2014 When expressed in insect cell microsomes, the relative intrinsic clearance values of the CYP2C9.58 variant for tolbutamide and losartan were quite similar to those of the typical defective variant CYP2C9.3, whereas the clearance value of CYP2C9.58 for diclofenac was slightly higher than that of another typical defective variant CYP2C9.2. Losartan 127-135 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 89-95 25977991-6 2015 CYP2C9 genotype and phenotype was determined in 148 Swedes and 146 Koreans using losartan as a probe. Losartan 81-89 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 0-6 25977991-7 2015 CYP2C9 enzyme activity was assessed using urinary losartan/metabolite E-3174 ratio. Losartan 50-58 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 0-6 25303293-0 2014 Relationship between the CYP2C9 IVS8-109A>T polymorphism and high losartan hydroxylation in healthy Ecuadorian volunteers. Losartan 69-77 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 25-31 25303293-1 2014 AIM: The CYP2C9 IVS8-109T allele was recently found to be more frequent among Swedish individuals, who have the highest losartan metabolic ratio (MR; losartan:E-3174). Losartan 120-128 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 9-15 25303293-1 2014 AIM: The CYP2C9 IVS8-109T allele was recently found to be more frequent among Swedish individuals, who have the highest losartan metabolic ratio (MR; losartan:E-3174). Losartan 150-158 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 9-15 25303293-2 2014 Thus, the influence of the CYP2C9 IVS8-109A>T polymorphism on the losartan MR was evaluated among healthy Ecuadorians. Losartan 69-77 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 27-33 25303293-7 2014 Further investigation needs to be carried out in order to clarify the relevance of the SNP of CYP2C9 IVS8-109A>T on losartan hydroxylation across populations and its potential implications in CYP2C9 activity. Losartan 119-127 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 94-100 25303293-7 2014 Further investigation needs to be carried out in order to clarify the relevance of the SNP of CYP2C9 IVS8-109A>T on losartan hydroxylation across populations and its potential implications in CYP2C9 activity. Losartan 119-127 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 195-201 25994031-1 2015 CYP2C9, one of the most important drug-metabolizing enzymes, is responsible for metabolizing approximately 15% of clinically important drugs, including warfarin, diclofenac, and losartan. Losartan 178-186 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 0-6 24986093-0 2014 Drug-drug interaction of losartan and glimepiride metabolism by recombinant microsome CYP2C9*1, 2C9*3, 2C9*13, and 2C9*16 in vitro. Losartan 25-33 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 86-92 24986093-2 2014 METHODS: In this study, we characterized the drug-drug interactions of losartan (LOS) and glimepiride (GLP) using recombinant cytochrome P450 (CYP) 2C9 enzymes (CYP2C9*1, CYP2C9*3, CYP2C9*13, and CYP2C9*16). Losartan 71-79 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 126-151 24986093-2 2014 METHODS: In this study, we characterized the drug-drug interactions of losartan (LOS) and glimepiride (GLP) using recombinant cytochrome P450 (CYP) 2C9 enzymes (CYP2C9*1, CYP2C9*3, CYP2C9*13, and CYP2C9*16). Losartan 71-79 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 161-167 24986093-2 2014 METHODS: In this study, we characterized the drug-drug interactions of losartan (LOS) and glimepiride (GLP) using recombinant cytochrome P450 (CYP) 2C9 enzymes (CYP2C9*1, CYP2C9*3, CYP2C9*13, and CYP2C9*16). Losartan 71-79 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 171-177 24986093-2 2014 METHODS: In this study, we characterized the drug-drug interactions of losartan (LOS) and glimepiride (GLP) using recombinant cytochrome P450 (CYP) 2C9 enzymes (CYP2C9*1, CYP2C9*3, CYP2C9*13, and CYP2C9*16). Losartan 71-79 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 171-177 24986093-2 2014 METHODS: In this study, we characterized the drug-drug interactions of losartan (LOS) and glimepiride (GLP) using recombinant cytochrome P450 (CYP) 2C9 enzymes (CYP2C9*1, CYP2C9*3, CYP2C9*13, and CYP2C9*16). Losartan 71-79 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 171-177 24986093-2 2014 METHODS: In this study, we characterized the drug-drug interactions of losartan (LOS) and glimepiride (GLP) using recombinant cytochrome P450 (CYP) 2C9 enzymes (CYP2C9*1, CYP2C9*3, CYP2C9*13, and CYP2C9*16). Losartan 81-84 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 126-151 24986093-2 2014 METHODS: In this study, we characterized the drug-drug interactions of losartan (LOS) and glimepiride (GLP) using recombinant cytochrome P450 (CYP) 2C9 enzymes (CYP2C9*1, CYP2C9*3, CYP2C9*13, and CYP2C9*16). Losartan 81-84 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 161-167 24986093-3 2014 RESULTS: Metabolism of losartan by recombinant CYP2C9* 1, CYP2C9*3, CYP2C9*13, and CYP2C9* 16 was inhibited by glimepiride competitively with IC50 values of 0.669 +- 0.055 microM, 0.424 +- 0.032 microM, 2.557 +- 0.058 microM, and 0.667 +- 0.039 microM, respectively. Losartan 23-31 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 47-53 24986093-3 2014 RESULTS: Metabolism of losartan by recombinant CYP2C9* 1, CYP2C9*3, CYP2C9*13, and CYP2C9* 16 was inhibited by glimepiride competitively with IC50 values of 0.669 +- 0.055 microM, 0.424 +- 0.032 microM, 2.557 +- 0.058 microM, and 0.667 +- 0.039 microM, respectively. Losartan 23-31 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 58-64 24986093-3 2014 RESULTS: Metabolism of losartan by recombinant CYP2C9* 1, CYP2C9*3, CYP2C9*13, and CYP2C9* 16 was inhibited by glimepiride competitively with IC50 values of 0.669 +- 0.055 microM, 0.424 +- 0.032 microM, 2.557 +- 0.058 microM, and 0.667 +- 0.039 microM, respectively. Losartan 23-31 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 58-64 24986093-3 2014 RESULTS: Metabolism of losartan by recombinant CYP2C9* 1, CYP2C9*3, CYP2C9*13, and CYP2C9* 16 was inhibited by glimepiride competitively with IC50 values of 0.669 +- 0.055 microM, 0.424 +- 0.032 microM, 2.557 +- 0.058 microM, and 0.667 +- 0.039 microM, respectively. Losartan 23-31 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 58-64 24986093-9 2014 CONCLUSIONS: Given these results, the potential inhibition of losartan metabolism by CYP2C9*3, CYP2C9*13, and CYP2C9*16 in vivo by glimepiride deserves further investigation. Losartan 62-70 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 85-91 24986093-9 2014 CONCLUSIONS: Given these results, the potential inhibition of losartan metabolism by CYP2C9*3, CYP2C9*13, and CYP2C9*16 in vivo by glimepiride deserves further investigation. Losartan 62-70 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 95-101 24986093-9 2014 CONCLUSIONS: Given these results, the potential inhibition of losartan metabolism by CYP2C9*3, CYP2C9*13, and CYP2C9*16 in vivo by glimepiride deserves further investigation. Losartan 62-70 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 95-101 23844998-0 2014 Effect of 36 CYP2C9 variants found in the Chinese population on losartan metabolism in vitro. Losartan 64-72 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 13-19 23844998-4 2014 The aim of this study was to assess the catalytic activities of 36 CYP2C9 variants found in the Chinese population toward losartan in vitro. Losartan 122-130 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 67-73 23844998-6 2014 Insect microsomes expressing the 36 CYP2C9 variants were incubated with 0.5-25 muM losartan for 30 min at 37 C. Next, the products were extracted, and signal detection was performed using high-performance liquid chromatography. Losartan 83-91 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 36-42 23844998-11 2014 These findings suggest that more attention should be paid to subjects carrying these infrequent CYP2C9 alleles when administering losartan in the clinic. Losartan 130-138 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 96-102 25075423-5 2014 When expressed in insect cell microsomes, the relative intrinsic clearance values of the CYP2C9.58 variant for tolbutamide and losartan were quite similar to those of the typical defective variant CYP2C9.3, whereas the clearance value of CYP2C9.58 for diclofenac was slightly higher than that of another typical defective variant CYP2C9.2. Losartan 127-135 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 197-203 25075423-5 2014 When expressed in insect cell microsomes, the relative intrinsic clearance values of the CYP2C9.58 variant for tolbutamide and losartan were quite similar to those of the typical defective variant CYP2C9.3, whereas the clearance value of CYP2C9.58 for diclofenac was slightly higher than that of another typical defective variant CYP2C9.2. Losartan 127-135 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 197-203 25075423-5 2014 When expressed in insect cell microsomes, the relative intrinsic clearance values of the CYP2C9.58 variant for tolbutamide and losartan were quite similar to those of the typical defective variant CYP2C9.3, whereas the clearance value of CYP2C9.58 for diclofenac was slightly higher than that of another typical defective variant CYP2C9.2. Losartan 127-135 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 197-203 22735459-5 2012 The CYP2C9*1/*3 subjects showed lower oral clearance (p < 0.001) of losartan and higher Cmax (p < 0.01) and longer half-life (p < 0.01) of E-3174 than the CYP2C9*1/*1 subjects. Losartan 71-79 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 4-10 23118328-7 2013 CYP2C9 variants were associated only with losartan pharmacokinetics: the half-life of losartan was higher in CYP2C9*3 allele carriers (3.1 +- 0.4 hours) than in volunteers with the wild-type genotype (2.3 +- 0.1 hours) (P <= 0.05). Losartan 42-50 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 0-6 23118328-7 2013 CYP2C9 variants were associated only with losartan pharmacokinetics: the half-life of losartan was higher in CYP2C9*3 allele carriers (3.1 +- 0.4 hours) than in volunteers with the wild-type genotype (2.3 +- 0.1 hours) (P <= 0.05). Losartan 42-50 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 109-115 23118328-7 2013 CYP2C9 variants were associated only with losartan pharmacokinetics: the half-life of losartan was higher in CYP2C9*3 allele carriers (3.1 +- 0.4 hours) than in volunteers with the wild-type genotype (2.3 +- 0.1 hours) (P <= 0.05). Losartan 86-94 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 0-6 23118328-7 2013 CYP2C9 variants were associated only with losartan pharmacokinetics: the half-life of losartan was higher in CYP2C9*3 allele carriers (3.1 +- 0.4 hours) than in volunteers with the wild-type genotype (2.3 +- 0.1 hours) (P <= 0.05). Losartan 86-94 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 109-115 23118328-9 2013 These results suggest that genotypes for CYP2C9 and CYP2C8 are relevant to the pharmacokinetics of losartan and valsartan, respectively, but not the pharmacokinetics of candesartan or telmisartan. Losartan 99-107 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 41-47 24800477-0 2013 [Relationship between warfarin dosing and activity of CYP2C9 assessed by the content of losartan and its metabolite E-3174 in the urine of patients with mechanical prosthetic heart valves]. Losartan 88-96 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 54-60 22735459-6 2012 However, AUC0- of losartan was greater in CYP2C9*1/*3 subjects than in CYP2C9*1/*1, but these results were not significant (p < 0.05, but statistical power < 0.8). Losartan 19-27 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 43-49 22735459-6 2012 However, AUC0- of losartan was greater in CYP2C9*1/*3 subjects than in CYP2C9*1/*1, but these results were not significant (p < 0.05, but statistical power < 0.8). Losartan 19-27 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 72-78 22735459-9 2012 CONCLUSION: These results suggest that CYP2C9*1/*3 and CYP2C9*1/*13 are similarly associated with decreased formation of E-3174 from losartan, but the clinical effects of losartan may not be reduced by CYP2C9*1/*3 and CYP2C9*1/*13. Losartan 133-141 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 39-45 22735459-9 2012 CONCLUSION: These results suggest that CYP2C9*1/*3 and CYP2C9*1/*13 are similarly associated with decreased formation of E-3174 from losartan, but the clinical effects of losartan may not be reduced by CYP2C9*1/*3 and CYP2C9*1/*13. Losartan 133-141 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 55-61 22735459-9 2012 CONCLUSION: These results suggest that CYP2C9*1/*3 and CYP2C9*1/*13 are similarly associated with decreased formation of E-3174 from losartan, but the clinical effects of losartan may not be reduced by CYP2C9*1/*3 and CYP2C9*1/*13. Losartan 133-141 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 55-61 22735459-9 2012 CONCLUSION: These results suggest that CYP2C9*1/*3 and CYP2C9*1/*13 are similarly associated with decreased formation of E-3174 from losartan, but the clinical effects of losartan may not be reduced by CYP2C9*1/*3 and CYP2C9*1/*13. Losartan 133-141 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 55-61 23118328-3 2013 The aim of this study is to evaluate the possible association between sex, polymorphisms in the CYP2C8 and CYP2C9 genes, and the pharmacokinetics of losartan, valsartan, candesartan, and telmisartan. Losartan 149-157 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 107-113 22735459-0 2012 Effects of CYP2C9*1/*3 and *1/*13 on the pharmacokinetics of losartan and its active metabolite E-3174. Losartan 61-69 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 11-17 22735459-1 2012 OBJECTIVE: The effects of CYP2C9*1/*3 and *1/*13 genotypes were evaluated on the pharmacokinetics of losartan and its active metabolite, E-3174, in Korean subjects. Losartan 101-109 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 26-32 22735459-4 2012 RESULTS: The CYP2C9*1/*13 subjects showed lower oral clearance (p < 0.001) and greater AUC0- (p < 0.01) of losartan and higher Cmax (p < 0.01) and longer half-life (p < 0.001) of E-3174 than the CYP2C9*1/*1 subjects, but AUC0- of E-3174 was not different. Losartan 114-122 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 13-19 21870106-7 2012 In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. Losartan 13-21 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 108-114 22294058-0 2012 Search for the molecular basis of ultra-rapid CYP2C9-catalysed metabolism: relationship between SNP IVS8-109A>T and the losartan metabolism phenotype in Swedes. Losartan 123-131 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 46-52 22483397-2 2012 CYP isoform specific substrates and their metabolites of CYP1A2 (caffeine), CYP2C9 (losartan), CYP2C19 (omeprazole), CYP2D6 (dextromethorphan) and CYP3A (midazolam) were all simultaneously analyzed using LC-MS/MS after administration of a mixture of five drugs (i.e., a "cocktail approach") to healthy volunteers. Losartan 84-92 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 76-82 21841812-0 2011 Frequency of CYP2C9 alleles in Koreans and their effects on losartan pharmacokinetics. Losartan 60-68 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 13-19 21841812-5 2011 The enzymatic activity of each CYP2C9 genotype was evaluated using losartan as the substrate. Losartan 67-75 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 31-37 21841812-8 2011 In the pharmacokinetics studies, the AUC(0- ) of losartan in CYP2C9*3/*3 subjects was 1.42-fold larger than that in CYP2C9*1/*1 subjects, and the AUC(0- ) of E-3174, a more active metabolite of losartan, in CYP2C9*3/*3 subjects was only 12% of that in CYP2C9*1/*1 subjects. Losartan 49-57 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 61-67 21841812-8 2011 In the pharmacokinetics studies, the AUC(0- ) of losartan in CYP2C9*3/*3 subjects was 1.42-fold larger than that in CYP2C9*1/*1 subjects, and the AUC(0- ) of E-3174, a more active metabolite of losartan, in CYP2C9*3/*3 subjects was only 12% of that in CYP2C9*1/*1 subjects. Losartan 49-57 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 116-122 21841812-8 2011 In the pharmacokinetics studies, the AUC(0- ) of losartan in CYP2C9*3/*3 subjects was 1.42-fold larger than that in CYP2C9*1/*1 subjects, and the AUC(0- ) of E-3174, a more active metabolite of losartan, in CYP2C9*3/*3 subjects was only 12% of that in CYP2C9*1/*1 subjects. Losartan 49-57 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 116-122 21841812-8 2011 In the pharmacokinetics studies, the AUC(0- ) of losartan in CYP2C9*3/*3 subjects was 1.42-fold larger than that in CYP2C9*1/*1 subjects, and the AUC(0- ) of E-3174, a more active metabolite of losartan, in CYP2C9*3/*3 subjects was only 12% of that in CYP2C9*1/*1 subjects. Losartan 49-57 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 116-122 21841812-10 2011 CYP2C9*3/*3 subjects metabolized much less losartan into E-3174 than CYP2C9*1/*1 subjects. Losartan 43-51 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 0-6 23093260-0 2012 Development of a HPLC method for the determination of losartan urinary metabolic ratio to be used for the determination of CYP2C9 hydroxylation phenotypes. Losartan 54-62 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 123-129 23093260-1 2012 BACKGROUND: Losartan is metabolized to losartan carboxylic acid (E-3174) by the polymorphic cytochrome CYP2C9. Losartan 12-20 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 103-109 23093260-6 2012 Analyses with the present HPLC method show significant differences (p<0.05) in losartan MRs between the four CYP2C9 genotype groups in 13 Spanish healthy volunteers. Losartan 82-90 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 112-118 23093260-8 2012 Therefore, it appears to be useful for CYP2C9 phenotyping using losartan as a drug test in populations, such as Hispanics with different allele combinations. Losartan 64-72 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 39-45 21182487-1 2011 CYP2C9 metabolizes more than 100 clinically used drugs including phenytoin, S-warfarin, tolbutamide, glipizide, diclofenac, and losartan with varying contributions. Losartan 128-136 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 0-6 21666702-10 2011 CONCLUSION: The significant increase in the AUC of losartan (9 mg/kg) by ticlopidine (10 mg/kg) could be attributed to the inhibition of CYP2C9- and 3A4-mediated losartan metabolism in small intestine and/or in liver. Losartan 51-59 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 137-143 21666702-10 2011 CONCLUSION: The significant increase in the AUC of losartan (9 mg/kg) by ticlopidine (10 mg/kg) could be attributed to the inhibition of CYP2C9- and 3A4-mediated losartan metabolism in small intestine and/or in liver. Losartan 162-170 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 137-143 21332946-0 2011 Effect of atorvastatin on CYP2C9 metabolic activity as measured by the formation rate of losartan metabolite in hypercholesterolaemic patients. Losartan 89-97 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 26-32 21332946-6 2011 Losartan was used as a probe drug to determine CYP2C9 metabolic activity. Losartan 0-8 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 47-53 21321060-0 2011 CYP2C9-mediated metabolic activation of losartan detected by a highly sensitive cell-based screening assay. Losartan 40-48 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 0-6 21321060-6 2011 Metabolic activation of losartan by CYP2C9 has never been reported, although the metabolic activations of benzbromarone and tienilic acid have been reported. Losartan 24-32 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 36-42 21321060-8 2011 Two CYP2C9-specific semicarbazide adducts of losartan (S1 and S2) were detected. Losartan 45-53 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 4-10 21321060-10 2011 In conclusion, a highly sensitive cell-based assay to evaluate CYP2C9-mediated metabolic activation was established, and we found for the first time that CYP2C9 is involved in the metabolic activation of losartan. Losartan 204-212 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 63-69 21321060-10 2011 In conclusion, a highly sensitive cell-based assay to evaluate CYP2C9-mediated metabolic activation was established, and we found for the first time that CYP2C9 is involved in the metabolic activation of losartan. Losartan 204-212 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 154-160 19903527-9 2010 The lower bioavailability of Losartan in the CYP2C9*1/*1 subjects than CYP2C9*1/*3 subjects was found and could be due to the variety of enzymatic activity. Losartan 29-37 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 45-51 19715737-1 2010 Human cytochrome P450 2C9 (CYP2C9) accounts for ~20% of hepatic total CYP content and metabolizes ~15% clinical drugs such as phenytoin, S-warfarin, tolbutamide, losartan, and many nonsteroidal anti-inflammatory agents (NSAIDs). Losartan 162-170 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 6-25 19715737-1 2010 Human cytochrome P450 2C9 (CYP2C9) accounts for ~20% of hepatic total CYP content and metabolizes ~15% clinical drugs such as phenytoin, S-warfarin, tolbutamide, losartan, and many nonsteroidal anti-inflammatory agents (NSAIDs). Losartan 162-170 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 27-33 20668444-4 2010 Whereas glucosamine had no significant effect on CYP activity, noscapine caused marked inhibition of CYP2C9 (4.9-fold increase in urinary losartan/E3174 ratio) and CYP2C19 (3.6-fold increase in the plasma omeprazole/5-hydroxyomeprazole ratio). Losartan 138-146 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 101-107 20405111-6 2010 On suspicion of ultra-high activity of CYP2C9, a phenotyping test for CYP2C9 with losartan was performed. Losartan 82-90 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 70-76 20405111-8 2010 CONCLUSIONS: Our finding of an ultrarapid metabolism of losartan and phenytoin may apply to other CYP2C9 substrates, where inhibition of CYP2C9 may cause severe adverse drug reactions. Losartan 56-64 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 98-104 20405111-8 2010 CONCLUSIONS: Our finding of an ultrarapid metabolism of losartan and phenytoin may apply to other CYP2C9 substrates, where inhibition of CYP2C9 may cause severe adverse drug reactions. Losartan 56-64 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 137-143 19903527-9 2010 The lower bioavailability of Losartan in the CYP2C9*1/*1 subjects than CYP2C9*1/*3 subjects was found and could be due to the variety of enzymatic activity. Losartan 29-37 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 71-77 19604036-0 2009 Effects of the CYP2C9*13 allele on the pharmacokinetics of losartan in healthy male subjects. Losartan 59-67 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 15-21 19593208-6 2009 A suggestive finding of less pronounced ambulatory BP response to losartan in CYP2C9*1*3 patients with low-normal kidney function was made. Losartan 66-74 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 78-84 19593208-1 2009 BACKGROUND: Two variants of the CYP2C9 gene, CYP2C9*2 and CYP2C9*3, have been indicated to have impaired enzyme function, and thus suspected to reduce the formation of the active metabolite of losartan. Losartan 193-201 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 32-38 19593208-1 2009 BACKGROUND: Two variants of the CYP2C9 gene, CYP2C9*2 and CYP2C9*3, have been indicated to have impaired enzyme function, and thus suspected to reduce the formation of the active metabolite of losartan. Losartan 193-201 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 45-51 19593208-1 2009 BACKGROUND: Two variants of the CYP2C9 gene, CYP2C9*2 and CYP2C9*3, have been indicated to have impaired enzyme function, and thus suspected to reduce the formation of the active metabolite of losartan. Losartan 193-201 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 45-51 19604036-1 2009 The aim of the study was to determine the pharmacokinetics of losartan in relation to the CYP2C9*13 allele. Losartan 62-70 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 90-96 19604036-7 2009 Compared with the subjects in the CYP2C9*1/*1 group, individuals carrying the CYP2C9*1/*13 genotype showed significantly a longer t(1/2) of losartan and E3174 and markedly increased the area under the curve (AUC) of losartan. Losartan 140-148 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 34-40 19604036-7 2009 Compared with the subjects in the CYP2C9*1/*1 group, individuals carrying the CYP2C9*1/*13 genotype showed significantly a longer t(1/2) of losartan and E3174 and markedly increased the area under the curve (AUC) of losartan. Losartan 140-148 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 78-84 19604036-7 2009 Compared with the subjects in the CYP2C9*1/*1 group, individuals carrying the CYP2C9*1/*13 genotype showed significantly a longer t(1/2) of losartan and E3174 and markedly increased the area under the curve (AUC) of losartan. Losartan 216-224 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 34-40 19604036-7 2009 Compared with the subjects in the CYP2C9*1/*1 group, individuals carrying the CYP2C9*1/*13 genotype showed significantly a longer t(1/2) of losartan and E3174 and markedly increased the area under the curve (AUC) of losartan. Losartan 216-224 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 78-84 19604036-9 2009 The ratio of AUC(E3174)/AUC(losartan) after losartan administration in the CYP2C9*1/*13 and CYP2C9*1/*3 groups was also statistically different from that in the CYP2C9*1/*1 group. Losartan 28-36 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 75-81 19604036-10 2009 The data indicate that the presence of the CYP2C9*13 allele results in poor metabolism of losartan after a single oral dose. Losartan 90-98 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 43-49 19669737-0 2009 CYP2C9 genotype and pharmacodynamic responses to losartan in patients with primary and secondary kidney diseases. Losartan 49-57 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 0-6 19541829-7 2009 For losartan oxidation, CYP2C9.13 and CYP2C9.28 showed 2.5- and 1.8-fold higher K(m) values, respectively, and all variants except for CYP2C9.34 showed >77% lower V(max) and intrinsic clearance values. Losartan 4-12 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 24-30 19541829-7 2009 For losartan oxidation, CYP2C9.13 and CYP2C9.28 showed 2.5- and 1.8-fold higher K(m) values, respectively, and all variants except for CYP2C9.34 showed >77% lower V(max) and intrinsic clearance values. Losartan 4-12 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 38-44 19541829-7 2009 For losartan oxidation, CYP2C9.13 and CYP2C9.28 showed 2.5- and 1.8-fold higher K(m) values, respectively, and all variants except for CYP2C9.34 showed >77% lower V(max) and intrinsic clearance values. Losartan 4-12 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 38-44 19925388-1 2009 Human cytochrome P450 2C9 (CYP2C9) accounts for approximately 20% of total hepatic CYP content and metabolizes approximately 15% clinically used drugs including S-warfarin, tolbutamide, phenytoin, losartan, diclofenac, and celecoxib. Losartan 197-205 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 6-25 19925388-1 2009 Human cytochrome P450 2C9 (CYP2C9) accounts for approximately 20% of total hepatic CYP content and metabolizes approximately 15% clinically used drugs including S-warfarin, tolbutamide, phenytoin, losartan, diclofenac, and celecoxib. Losartan 197-205 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 27-33 19669737-4 2009 AIM: The study aims were to determine whether CYP2C9 variant alleles (*2 and *3) altered urinary protein excretion, glomerular filtration rate, and blood pressure in Caucasian patients prescribed losartan. Losartan 196-204 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 46-52 19669737-8 2009 CONCLUSION: These preliminary results suggest a possible influence of CYP2C9 genotype on proteinuria and blood pressure in Caucasian CKD patients treated with losartan. Losartan 159-167 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 70-76 19221727-4 2009 RESULTS: The area under the plasma concentration-time curve (AUC) of losartan increased significantly following a 14-day silymarin treatment in subjects with the CYP2C9*1/*1 genotype, but not in those with the CYP2C9*1/*3 genotype. Losartan 69-77 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 162-168 19221727-4 2009 RESULTS: The area under the plasma concentration-time curve (AUC) of losartan increased significantly following a 14-day silymarin treatment in subjects with the CYP2C9*1/*1 genotype, but not in those with the CYP2C9*1/*3 genotype. Losartan 69-77 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 210-216 19221727-6 2009 The metabolic ratio of losartan (ratio of AUC(0-infinity) of E-3174 to AUC(0-infinity) of losartan) decreased significantly after a 14-day treatment with silymarin in individuals with the CYP2C9*1/*1 genotype (p < 0.05), but not in those with the CYP2C9*1/*3 genotype (p = 0.065). Losartan 23-31 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 188-194 19221727-6 2009 The metabolic ratio of losartan (ratio of AUC(0-infinity) of E-3174 to AUC(0-infinity) of losartan) decreased significantly after a 14-day treatment with silymarin in individuals with the CYP2C9*1/*1 genotype (p < 0.05), but not in those with the CYP2C9*1/*3 genotype (p = 0.065). Losartan 23-31 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 250-256 18971529-0 2008 Genetic variations of CYP2C9 in 724 Japanese individuals and their impact on the antihypertensive effects of losartan. Losartan 109-117 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 22-28 18816302-0 2008 Disposition of a CYP2C9 phenotyping agent, losartan, is not influenced by the common 3435C > T variation of the drug transporter gene ABCB1 (MDR1). Losartan 43-51 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 17-23 18816302-1 2008 Losartan is oxidized to E3174 by cytochrome P450 2C9 (CYP2C9); it has been suggested as a useful probe drug for CYP2C9 activity. Losartan 0-8 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 33-52 18816302-1 2008 Losartan is oxidized to E3174 by cytochrome P450 2C9 (CYP2C9); it has been suggested as a useful probe drug for CYP2C9 activity. Losartan 0-8 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 54-60 18816302-1 2008 Losartan is oxidized to E3174 by cytochrome P450 2C9 (CYP2C9); it has been suggested as a useful probe drug for CYP2C9 activity. Losartan 0-8 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 112-118 18971529-1 2008 CYP2C9, a drug-metabolizing enzyme, converts the angiotensin II receptor blocker losartan to its active form, which is responsible for its antihypertensive effect. Losartan 81-89 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 0-6 18971529-5 2008 After 3 months of losartan treatment, systolic blood pressure was not lowered in two patients with CYP2C9* 1/*30, suggesting that they exhibited impaired in vivo CYP2C9 activity. Losartan 18-26 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 162-168 18971529-6 2008 CYP2C9*30 might be associated with a diminished response to the antihypertensive effects of losartan. Losartan 92-100 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 0-6 18445991-0 2008 The effect of bucolome, a CYP2C9 inhibitor, on the pharmacokinetics of losartan. Losartan 71-79 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 26-32 18445991-1 2008 Losartan, a selective angiotensin receptor antagonist, is mainly metabolized by CYP2C9 to an active carboxylic acid, E3174, which is pharmacologically more potent inhibitor than the parent compound. Losartan 0-8 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 80-86 17516991-4 2007 The aim of this study was to evaluate the inhibitory effect of valproic acid on cytochrome P450 2C9 (CYP2C9) activity by using losartan oxidation as a probe in epilepsy patients. Losartan 127-135 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 80-99 17516991-4 2007 The aim of this study was to evaluate the inhibitory effect of valproic acid on cytochrome P450 2C9 (CYP2C9) activity by using losartan oxidation as a probe in epilepsy patients. Losartan 127-135 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 101-107 17516991-7 2007 Losartan and E3174, the CYP2C9-derived carboxylic acid metabolite of losartan in 8 hr urine were assayed by using high pressure liquid chromatography. Losartan 69-77 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 24-30 17305793-0 2007 CYP2C9 variant modifies blood pressure-lowering response to losartan in Type 1 diabetic patients with nephropathy. Losartan 60-68 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 0-6 16783563-0 2006 Amodiaquine, its desethylated metabolite, or both, inhibit the metabolism of debrisoquine (CYP2D6) and losartan (CYP2C9) in vivo. Losartan 103-111 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 113-119 17344941-4 2007 Losartan metabolism has been suggested as a marker for determination of CYP2C9 activity. Losartan 0-8 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 72-78 16783563-8 2006 The CYP2D6 and CYP2C9 activities of the subjects were measured by debrisoquine and losartan phenotyping tests, respectively. Losartan 83-91 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 15-21 16635054-1 2006 BACKGROUND: CYP2C9 is one of the major drug metabolizing enzymes for many drugs including warfarin, NSAIDs and losartan. Losartan 111-119 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 12-18 16278191-3 2005 The formation of norketobemidone from ketobemidone (1 microM) correlated best with CYP2C9 activity, measured as losartan oxidation (rs = 0.82, n = 19, p < 0.001), but there was also a strong correlation with CYP3A4 activity. Losartan 112-120 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 83-89 16445595-3 2006 Losartan was used as a marker to assess CYP2C9 activity. Losartan 0-8 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 40-46 15100169-5 2004 In CYP2C9 phenotyping with losartan, three subpopulations were distinguished that differed in the number of CYP2C9*3 alleles (0, 1, or 2). Losartan 27-35 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 3-9 15592335-2 2004 METHODS: The frequency of coadministration between losartan and well-established cytochrome P450 (CYP) 2C9 inhibitors, as well as codeine and tramadol and CYP2D6 inhibitors, was studied by use of data from a university hospital medication database. Losartan 51-59 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 81-106 29793229-5 2004 CYP2C9 metabolizes several oral hypoglycemics, oral anticoagulants, non-steroidal anti-inflammatory drugs and other drugs, including phenytoin, losartan, fluvastatin, and torsemide. Losartan 144-152 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 0-6 15289788-1 2004 UNLABELLED: Background and aim Previous data indicate that the urinary losartan/E-3174 ratio is a marker for cytochrome P450 (CYP) 2C9 activity in vivo. Losartan 71-79 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 109-134 15289788-3 2004 METHODS: A single oral dose of losartan (25 mg) was given to 19 Beninese subjects with CYP2C9*1/*1 (n = 9), *1/*5 (n = 1), *1/*6 (n = 1), *1/*8 (n = 2), *1/*11 (n = 3), *5/*6 (n = 1), *5/*8 (n = 1), and *8/*11 (n = 1) genotypes. Losartan 31-39 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 87-93 15289788-6 2004 RESULTS: The urinary losartan/E-3174 ratio in the various genotypes was as follows: 1.85 +/- 2.4 (mean +/- SD) for CYP2C9*1/*1, 14.6 for CYP2C9*1/*5, 4.2 for CYP2C9*1/*6, 188 for CYP2C9*5/*6, 11.6 for CYP2C9*5/*8, 0.44 +/- 0.13 (mean +/- SD) for CYP2C9*1/*8, 2.2 for CYP2C9*8/*11, and 5.72 +/- 4.5 (mean +/- SD) for CYP2C9*1/*11. Losartan 21-29 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 115-121 15289788-8 2004 The urinary losartan/E-3174 ratio of the single CYP2C9*1/*6 subject was higher than the 95% confidence interval of the mean of the CYP2C9*1/*1 group (0.0-3.7), whereas the metabolic ratio of the CYP2C9*8/*11 carrier was inside the 95% confidence interval of the means of the CYP2C9*1/*1 and CYP2C9*1/*11 groups (0.0-18). Losartan 12-20 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 48-54 15289788-8 2004 The urinary losartan/E-3174 ratio of the single CYP2C9*1/*6 subject was higher than the 95% confidence interval of the mean of the CYP2C9*1/*1 group (0.0-3.7), whereas the metabolic ratio of the CYP2C9*8/*11 carrier was inside the 95% confidence interval of the means of the CYP2C9*1/*1 and CYP2C9*1/*11 groups (0.0-18). Losartan 12-20 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 131-137 15289788-8 2004 The urinary losartan/E-3174 ratio of the single CYP2C9*1/*6 subject was higher than the 95% confidence interval of the mean of the CYP2C9*1/*1 group (0.0-3.7), whereas the metabolic ratio of the CYP2C9*8/*11 carrier was inside the 95% confidence interval of the means of the CYP2C9*1/*1 and CYP2C9*1/*11 groups (0.0-18). Losartan 12-20 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 131-137 15289788-8 2004 The urinary losartan/E-3174 ratio of the single CYP2C9*1/*6 subject was higher than the 95% confidence interval of the mean of the CYP2C9*1/*1 group (0.0-3.7), whereas the metabolic ratio of the CYP2C9*8/*11 carrier was inside the 95% confidence interval of the means of the CYP2C9*1/*1 and CYP2C9*1/*11 groups (0.0-18). Losartan 12-20 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 131-137 15289788-8 2004 The urinary losartan/E-3174 ratio of the single CYP2C9*1/*6 subject was higher than the 95% confidence interval of the mean of the CYP2C9*1/*1 group (0.0-3.7), whereas the metabolic ratio of the CYP2C9*8/*11 carrier was inside the 95% confidence interval of the means of the CYP2C9*1/*1 and CYP2C9*1/*11 groups (0.0-18). Losartan 12-20 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 131-137 15197523-6 2004 Losartan oxidation was also studied in vitro, using human CYP2C8 and CYP2C9 enzymes expressed in yeast. Losartan 0-8 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 69-75 15197523-8 2004 The urinary losartan/E3174 ratio was significantly higher in subjects with CYP2C9*1/*3 genotype (median 2.35, n=12) than in subjects with CYP2C9*1/*1 (0.71, n=58) and *1/*2 (0.85, n=10) genotypes ( P<0.05). Losartan 12-20 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 75-81 15197523-8 2004 The urinary losartan/E3174 ratio was significantly higher in subjects with CYP2C9*1/*3 genotype (median 2.35, n=12) than in subjects with CYP2C9*1/*1 (0.71, n=58) and *1/*2 (0.85, n=10) genotypes ( P<0.05). Losartan 12-20 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 138-144 15197523-10 2004 CONCLUSION: The urinary losartan to E3174 metabolic ratio after a 25-mg losartan dose was found to be a safe and useful phenotyping assay for CYP2C9 activity in vivo. Losartan 24-32 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 142-148 15197523-11 2004 CYP2C9*3 variant allele is a major determinant of the enzyme activity, and it decreases losartan metabolism significantly, while CYP2C9*2 allele has less impact on enzyme function. Losartan 88-96 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 0-6 15197523-11 2004 CYP2C9*3 variant allele is a major determinant of the enzyme activity, and it decreases losartan metabolism significantly, while CYP2C9*2 allele has less impact on enzyme function. Losartan 88-96 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 129-135 15197523-2 2004 Losartan has recently been suggested as a selective probe for CYP2C9 metabolic activity. Losartan 0-8 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 62-68 15197523-3 2004 The aim of the study was to determine the activity of CYP2C9, using losartan as a probe drug, in relation to CYP2C9 genotype in healthy Turkish subjects. Losartan 68-76 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 54-60 15197523-3 2004 The aim of the study was to determine the activity of CYP2C9, using losartan as a probe drug, in relation to CYP2C9 genotype in healthy Turkish subjects. Losartan 68-76 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 109-115 15100169-6 2004 A three-fold higher metabolic ratio (MR; urinary losartan/carboxymetabolite) was found comparing CYP2C9*1/*3 (n = 20) to CYP2C9*1/*1 (n = 81), but there was considerable variation within each genotype. Losartan 49-57 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 97-103 15100169-6 2004 A three-fold higher metabolic ratio (MR; urinary losartan/carboxymetabolite) was found comparing CYP2C9*1/*3 (n = 20) to CYP2C9*1/*1 (n = 81), but there was considerable variation within each genotype. Losartan 49-57 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 121-127 15100169-7 2004 Subjects genotyped as CYP2C9*1/*1, but with an unexpectedly slow oxidation of losartan, were selected for DNA-sequencing analysis of the CYP2C9 gene. Losartan 78-86 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 22-28 12520632-0 2003 Tolbutamide, flurbiprofen, and losartan as probes of CYP2C9 activity in humans. Losartan 31-39 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 53-59 14600250-1 2004 Human CYP2C9 is important in the metabolism of numerous clinically used drugs such as the anticoagulant warfarin, the anticonvulsant phenytoin, antidiabetic drugs such as tolbutamide and glipizide, the hypertensive agent losartan, and numerous nonsteroidal anti-inflammatory drugs. Losartan 221-229 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 6-12 14504849-0 2003 Effect of the single CYP2C9*3 allele on pharmacokinetics and pharmacodynamics of losartan in healthy Japanese subjects. Losartan 81-89 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 21-27 14504849-1 2003 OBJECTIVE: Losartan is metabolized to the active carboxylic acid metabolite EXP3174 by CYP2C9. Losartan 11-19 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 87-93 14504849-2 2003 In this study, we determined the effects of the single CYP2C9*3 variant on the pharmacokinetics and pharmacodynamics of losartan. Losartan 120-128 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 55-61 14504849-11 2003 CONCLUSION: The single CYP2C9*3 variant reduces the metabolism of losartan and its hypotensive effect. Losartan 66-74 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 23-29 12899669-3 2003 Aethinyloestradiol was found to be a potent inhibitor (55% mean inhibition; 95% CI 32% to 79%) of losartan oxidation (CYP2C9) and R-omeprazole 5-hydroxylation (70%; 63% to 77%) (CYP2C19), while it had little effect on R-omeprazole sulphoxidation (CYP3A4) activity. Losartan 98-106 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 118-124 12820813-0 2003 Losartan and E3174 pharmacokinetics in cytochrome P450 2C9*1/*1, *1/*2, and *1/*3 individuals. Losartan 0-8 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 39-58 12820813-8 2003 A significant association between CYP2C9 genotype and losartan to E3174 formation clearance was observed, such that 50% of the variability was accounted for by the genotype. Losartan 54-62 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 34-40 12820813-11 2003 Alterations in losartan dosing in CYP2C9*1/*2 and *1/*3 individuals does not appear necessary. Losartan 15-23 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 34-40 12520632-5 2003 The formation clearance of tolbutamide to its CYP2C9-mediated metabolites demonstrated a stronger association with genotype compared to flurbiprofen and losartan, respectively (r2 = 0.64 vs. 0.53 vs. 0.42). Losartan 153-161 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 46-52 12359989-3 2002 The CYP2C9 genotype is known to determine sensitivity to and dose requirements for both warfarin and phenytoin, and also the rate of metabolism of losartan. Losartan 147-155 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 4-10 12359989-1 2002 BACKGROUND: The cytochrome P450 CYP2C9 enzyme (CYP2C9) metabolizes many clinically important drugs, for example, phenytoin, warfarin and the angiotensin II type 1 (AT(1)) receptor antagonists, losartan and irbesartan. Losartan 193-201 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 32-38 12359989-1 2002 BACKGROUND: The cytochrome P450 CYP2C9 enzyme (CYP2C9) metabolizes many clinically important drugs, for example, phenytoin, warfarin and the angiotensin II type 1 (AT(1)) receptor antagonists, losartan and irbesartan. Losartan 193-201 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 47-53 12235444-3 2002 Losartan, an antihypertensive agent, is also a substrate for CYP2C9. Losartan 0-8 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 61-67 12235444-10 2002 In the 14 CYP2C9*1/*1 subjects, the mean AUC(0-24) of losartan was increased by 29% (284 +/- 84 ng x h/mL versus 402 +/- 128 ng x h/mL; P =.008). Losartan 54-62 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 10-16 12235444-12 2002 CONCLUSIONS: Losartan, a CYP2C9 substrate, had no effect on the pharmacokinetics of phenytoin. Losartan 13-21 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 25-31 12235444-13 2002 However, phenytoin inhibited the CYP2C9-mediated conversion of losartan to E3174. Losartan 63-71 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 33-39 12207639-0 2002 Intra-individual variability in urinary losartan oxidation ratio, an in vivo marker of CYP2C9 activity. Losartan 40-48 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 87-93 12405866-18 2002 Losartan may have increased effect when coadministered with ritonavir and nelfinavir because of the induction of CYP2C9 and the expected increase in formation of the active metabolite, E-3174. Losartan 0-8 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 113-119 11823761-0 2002 Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype. Losartan 20-28 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 74-80 11823761-1 2002 BACKGROUND AND AIM: Losartan is metabolized by polymorphic CYP2C9 to E-3174. Losartan 20-28 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 59-65 11823761-2 2002 Our aim was to evaluate the pharmacokinetics of losartan and E-3174 in relation to the CYP2C9 genotype. Losartan 48-56 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 87-93 11823761-3 2002 METHODS: A 50-mg oral dose of losartan was given to 22 Swedish volunteers with different CYP2C9 genotypes. Losartan 30-38 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 89-95 11823761-7 2002 The ratio of the total losartan area under the plasma concentration-time curve (AUC) to the total E-3174 AUC (AUC(losartan)/AUC(E-3174)) was higher in the subject with the CYP2C9*3/*3 genotype (30-fold) and also in the CYP2C9*1/*3 and *2/*3 groups (approximately 2- and 3-fold, respectively) compared with the CYP2C9*1/*1 group. Losartan 23-31 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 172-178 11823761-7 2002 The ratio of the total losartan area under the plasma concentration-time curve (AUC) to the total E-3174 AUC (AUC(losartan)/AUC(E-3174)) was higher in the subject with the CYP2C9*3/*3 genotype (30-fold) and also in the CYP2C9*1/*3 and *2/*3 groups (approximately 2- and 3-fold, respectively) compared with the CYP2C9*1/*1 group. Losartan 23-31 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 219-225 11823761-7 2002 The ratio of the total losartan area under the plasma concentration-time curve (AUC) to the total E-3174 AUC (AUC(losartan)/AUC(E-3174)) was higher in the subject with the CYP2C9*3/*3 genotype (30-fold) and also in the CYP2C9*1/*3 and *2/*3 groups (approximately 2- and 3-fold, respectively) compared with the CYP2C9*1/*1 group. Losartan 23-31 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 219-225 11823761-7 2002 The ratio of the total losartan area under the plasma concentration-time curve (AUC) to the total E-3174 AUC (AUC(losartan)/AUC(E-3174)) was higher in the subject with the CYP2C9*3/*3 genotype (30-fold) and also in the CYP2C9*1/*3 and *2/*3 groups (approximately 2- and 3-fold, respectively) compared with the CYP2C9*1/*1 group. Losartan 114-122 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 172-178 11823761-10 2002 CONCLUSION: The CYP2C9*3 allele was shown to be associated with decreased formation of E-3174 from losartan. Losartan 99-107 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 16-22 11823761-11 2002 The significant differences between genotypes in plasma and urine losartan/E-3174 ratios and the good correlation between the plasma and urine ratios suggest that the losartan/E-3174 ratio in 0- to 8-hour urine specimens may serve as a phenotyping assay for CYP2C9 activity. Losartan 167-175 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 258-264 12081638-3 2002 The aim of this pilot study was to clarify if PR has an effect on losartan oxidation used as a measure of CYP2C9 activity. Losartan 66-74 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 106-112