PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 30085944-16 2018 CYP2B6 variants had more influence than POR variants on ketamine metabolism. Ketamine 56-64 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 0-6 30085944-0 2018 Stereoselective Ketamine Metabolism by Genetic Variants of Cytochrome P450 CYP2B6 and Cytochrome P450 Oxidoreductase. Ketamine 16-24 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 75-81 30085944-1 2018 WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Human ketamine N-demethylation to norketamine in vitro at therapeutic concentrations is catalyzed predominantly by the cytochrome P4502B6 isoform (CYP2B6). Ketamine 98-106 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 239-245 30085944-3 2018 CYP2B6.6, the protein encoded by the common variant allele CYP2B6*6, exhibits diminished ketamine metabolism in vitro compared with wild-type CYP2B6.1. Ketamine 89-97 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 0-6 30085944-3 2018 CYP2B6.6, the protein encoded by the common variant allele CYP2B6*6, exhibits diminished ketamine metabolism in vitro compared with wild-type CYP2B6.1. Ketamine 89-97 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 59-65 30085944-3 2018 CYP2B6.6, the protein encoded by the common variant allele CYP2B6*6, exhibits diminished ketamine metabolism in vitro compared with wild-type CYP2B6.1. Ketamine 89-97 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 59-65 30085944-5 2018 This investigation evaluated ketamine metabolism by genetic variants of human CYP2B6 and POR. Ketamine 29-37 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 78-84 30085944-18 2018 CONCLUSIONS: Genetic variants of CYP2B6 and P450 oxidoreductase have diminished ketamine N-demethylation activity, without affecting the stereoselectivity of metabolism. Ketamine 80-88 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 33-39 30085944-19 2018 These results suggest candidate genetic polymorphisms of CYP2B6 and P450 oxidoreductase for clinical evaluation to assess consequences for ketamine pharmacokinetics, elimination, bioactivation, and therapeutic effects. Ketamine 139-147 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 57-63 28737446-9 2018 The fm, CYP2B6 values for artemisinin, bupropion, clopidogrel, ketamine, selegiline, sertraline and ticlopidine were 0.24, 0.28, 0.15, 0.45, 0.46, 0.42 and 0.54, respectively, in HLM determined by chemical inhibition method. Ketamine 63-71 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 8-14 28737446-10 2018 The fm, CYP2B6 values for artemisinin, bupropion, clopidogrel, ketamine, selegiline, sertraline and ticlopidine were 0.46, 0.17, 0.15, 0.60, 0.51, 0.66 and 0.77, respectively, in HLM determined by chemical inhibition method in the presence of BSA (0.5% w/v). Ketamine 63-71 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 8-14 27763887-13 2016 CONCLUSIONS: These results show that while the CYP2B6*6 polymorphism results in diminished ketamine metabolism in vitro, this allelic variant did not affect single, low-dose ketamine metabolism, clearance, and pharmacokinetics in vivo. Ketamine 91-99 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 47-53 28252572-2 2017 OBJECTIVES: The aim of the study was to investigate the feasibility and sample sizes required to explore the relationship between CYP2B6*6 and GRIN2B single-nucleotide polymorphisms and ketamine-induced EP. Ketamine 186-194 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 130-136 29621538-9 2018 These results suggest a positive feedback loop by which estrogens can augment the effects of ketamine and its (2R,6R)-HNK and (2S,6S)-HNK metabolites on the ERalpha-induced transcription of CYP2A6 and CYP2B6, estrogen inducible enzymes that catalyze ketamine"s biotransformation to form the two active metabolites. Ketamine 93-101 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 201-207 28858450-4 2017 A small body of literature indicates that drugs that induce cytochrome P450 (CYP)2B6 and CYP3A4 will reduce exposure to ketamine and that drugs that inhibit these enzymes will increase exposure to ketamine. Ketamine 120-128 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 60-84 28858450-5 2017 Common genetic polymorphisms of the CYP2B6 gene may also be associated with variations in the exposure to ketamine. Ketamine 106-114 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 36-42 27763886-0 2016 CYP2B6*6 or Not CYP2B6*6-That Remains a Question for Precision Medicine and Ketamine! Ketamine 76-84 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 0-6 27763886-0 2016 CYP2B6*6 or Not CYP2B6*6-That Remains a Question for Precision Medicine and Ketamine! Ketamine 76-84 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 16-22 27763887-1 2016 BACKGROUND: At therapeutic concentrations, cytochrome P4502B6 (CYP2B6) is the major P450 isoform catalyzing hepatic ketamine N-demethylation to norketamine in vitro. Ketamine 116-124 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 63-69 27763887-4 2016 CYP2B6.6, the protein encoded by the CYP2B6*6 allele, and liver microsomes from CYP2B6*6 carriers had diminished ketamine metabolism in vitro. Ketamine 113-121 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 0-6 27763887-4 2016 CYP2B6.6, the protein encoded by the CYP2B6*6 allele, and liver microsomes from CYP2B6*6 carriers had diminished ketamine metabolism in vitro. Ketamine 113-121 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 37-43 27763887-4 2016 CYP2B6.6, the protein encoded by the CYP2B6*6 allele, and liver microsomes from CYP2B6*6 carriers had diminished ketamine metabolism in vitro. Ketamine 113-121 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 37-43 27763887-5 2016 This investigation tested whether humans with the CYP2B6*6 allele would have decreased clinical ketamine metabolism and clearance. Ketamine 96-104 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 50-56 27362518-8 2016 CYP2B6 catalyzes propofol and ketamine metabolism. Ketamine 30-38 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 0-6 27709010-5 2016 CYP2B6 has been demonstrated to play a role in the metabolism of 2%-10% of clinically used drugs including widely used antineoplastic agents cyclophosphamide and ifosfamide, anesthetics propofol and ketamine, synthetic opioids pethidine and methadone, and the antiretrovirals nevirapine and efavirenz, among others. Ketamine 199-207 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 0-6 27362518-9 2016 CYP2B6*6 allele is associated with decreased propofol and ketamine metabolism and increased adverse effects. Ketamine 58-66 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 0-6 22023129-7 2011 For all 3 species, inhibitors of CYP3A4, CYP2A6, CYP2C19, CYP2B6, and CYP2C9 diminished N-demethylation of ketamine. Ketamine 107-115 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 58-64 25702819-0 2015 CYP2B6*6 allele and age substantially reduce steady-state ketamine clearance in chronic pain patients: impact on adverse effects. Ketamine 58-66 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 0-6 25702819-2 2015 The CYP2B6*6 allele is associated with substantially reduced ketamine metabolism in vitro and, therefore, may affect ketamine clearance. Ketamine 61-69 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 4-10 25702819-2 2015 The CYP2B6*6 allele is associated with substantially reduced ketamine metabolism in vitro and, therefore, may affect ketamine clearance. Ketamine 117-125 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 4-10 25702819-3 2015 Our aims were to examine the impact of the CYP2B6*6 allele on ketamine plasma clearance and on adverse effects in chronic pain patients. Ketamine 62-70 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 43-49 25702819-4 2015 METHODS: CYP2B6 genotypes were identified in 49 chronic pain patients who received 24 h continuous subcutaneous infusions of ketamine. Ketamine 125-133 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 9-15 25702819-6 2015 RESULTS: The median plasma clearance of ketamine after 100 mg 24 h(-1) dose was significantly lower in patients with the CYP2B6*6/*6 (21.6 l h(-1) ) and CYP2B6*1/*6 (40.6 l h(-1) ) genotypes compared with patients with the CYP2B6*1/*1 genotype (68.1 l h(-1) , P < 0.001). Ketamine 40-48 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 121-127 25702819-6 2015 RESULTS: The median plasma clearance of ketamine after 100 mg 24 h(-1) dose was significantly lower in patients with the CYP2B6*6/*6 (21.6 l h(-1) ) and CYP2B6*1/*6 (40.6 l h(-1) ) genotypes compared with patients with the CYP2B6*1/*1 genotype (68.1 l h(-1) , P < 0.001). Ketamine 40-48 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 153-159 25702819-6 2015 RESULTS: The median plasma clearance of ketamine after 100 mg 24 h(-1) dose was significantly lower in patients with the CYP2B6*6/*6 (21.6 l h(-1) ) and CYP2B6*1/*6 (40.6 l h(-1) ) genotypes compared with patients with the CYP2B6*1/*1 genotype (68.1 l h(-1) , P < 0.001). Ketamine 40-48 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 153-159 25702819-7 2015 The ketamine : norketamine plasma metabolic ratio was significantly higher in patients with the CYP2B6*6/*6 genotype than in those with the CYP2B6*1/*6 and the CYP2B6*1/*1 genotypes (P < 0.001). Ketamine 4-12 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 96-102 25702819-7 2015 The ketamine : norketamine plasma metabolic ratio was significantly higher in patients with the CYP2B6*6/*6 genotype than in those with the CYP2B6*1/*6 and the CYP2B6*1/*1 genotypes (P < 0.001). Ketamine 4-12 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 140-146 25702819-7 2015 The ketamine : norketamine plasma metabolic ratio was significantly higher in patients with the CYP2B6*6/*6 genotype than in those with the CYP2B6*1/*6 and the CYP2B6*1/*1 genotypes (P < 0.001). Ketamine 4-12 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 140-146 25702819-11 2015 CONCLUSIONS: The CYP2B6*6 allele is associated with a substantial decrease in steady-state ketamine plasma clearance in chronic pain patients. Ketamine 91-99 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 17-23 23550066-0 2013 The CYP2B6*6 allele significantly alters the N-demethylation of ketamine enantiomers in vitro. Ketamine 64-72 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 4-10 23550066-1 2013 Ketamine is primarily metabolized to norketamine by hepatic CYP2B6 and CYP3A4-mediated N-demethylation. Ketamine 0-8 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 60-66 23550066-3 2013 The CYP2B6*6 allele is associated with reduced enzyme expression and activity that may lead to interindividual variability in ketamine metabolism. Ketamine 126-134 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 4-10 23550066-8 2013 The intrinsic clearance for both ketamine enantiomers by the high-affinity enzyme in HLMs with CYP2B6*1/*1 genotype were at least 2-fold and 6-fold higher, respectively, than those for CYP2B6*1/*6 genotype and CYP2B6*6/*6 genotype. Ketamine 33-41 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 95-101 23550066-8 2013 The intrinsic clearance for both ketamine enantiomers by the high-affinity enzyme in HLMs with CYP2B6*1/*1 genotype were at least 2-fold and 6-fold higher, respectively, than those for CYP2B6*1/*6 genotype and CYP2B6*6/*6 genotype. Ketamine 33-41 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 185-191 23550066-8 2013 The intrinsic clearance for both ketamine enantiomers by the high-affinity enzyme in HLMs with CYP2B6*1/*1 genotype were at least 2-fold and 6-fold higher, respectively, than those for CYP2B6*1/*6 genotype and CYP2B6*6/*6 genotype. Ketamine 33-41 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 185-191 23550066-12 2013 These results indicate a major role of CYP2B6 in ketamine N-demethylation in vitro and a significant impact of the CYP2B6*6 allele on enzyme-ketamine binding and catalytic activity. Ketamine 49-57 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 39-45 23550066-12 2013 These results indicate a major role of CYP2B6 in ketamine N-demethylation in vitro and a significant impact of the CYP2B6*6 allele on enzyme-ketamine binding and catalytic activity. Ketamine 141-149 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 115-121 23467454-3 2013 Drugs metabolized mainly by CYP2B6 include artemisinin, bupropion, cyclophosphamide, efavirenz, ketamine, and methadone. Ketamine 96-104 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 28-34 22023129-8 2011 Anti-CYP3A4, anti-CYP2C9, and anti-CYP2B6 antibodies also inhibited ketamine N-demethylation. Ketamine 68-76 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 35-41 21716267-1 2011 This study examined drug-drug interactions of oral S-ketamine with the cytochrome P450 (CYP) 2B6 inhibitor ticlopidine and the CYP3A inhibitor itraconazole. Ketamine 51-61 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 71-96 21508826-10 2011 CONCLUSIONS: : A novel observation is the large effect of rifampicin on S-norketamine concentrations and indicates that rifampicin induces the elimination of S-ketamine"s metabolite, S-norketamine, probably via induction of the CYP3A4 and/or CYP2B6 enzymes. Ketamine 158-168 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 242-248 20609441-7 2010 The kinetic data of ketamine N-demethylation with CYP3A4 and CYP2B6 were best described with the Michaelis-Menten model and the Hill equation, respectively. Ketamine 20-28 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 61-67 19702527-4 2009 CYP2B6 can metabolise approximately 8% of clinically used drugs (n > 60), including cyclophosphamide, ifosfamide, tamoxifen, ketamine, artemisinin, nevirapine, efavirenz, bupropion, sibutramine, and propofol. Ketamine 128-136 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 0-6 19442086-6 2009 CYP2B6, CYP3A4 and CYP2C9 play a relevant role in the metabolism of ketamine. Ketamine 68-76 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 0-6 17073575-2 2006 For bupropion, cyclophosphamide, ifosfamide, pethidine, ketamine and propofol, these reactions represent major metabolic or activation pathways and for their kinetics CYP2B6 function is of considerable importance. Ketamine 56-64 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 167-173 18781911-5 2008 These individual differences may result in variable systemic exposure to drugs metabolized by CYP2B6, including the antineoplastics cyclophosphamide and ifosfamide, the antiretrovirals nevirapine and efavirenz, the anesthetics propofol and ketamine, the synthetic opioid methadone, and the anti-Parkinsonian selegiline. Ketamine 240-248 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 94-100 30589555-0 2019 Halogen Substitution Influences Ketamine Metabolism by Cytochrome P450 2B6: In Vitro and Computational Approaches. Ketamine 32-40 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 55-74 11353758-0 2001 Involvement of CYP2B6 in n-demethylation of ketamine in human liver microsomes. Ketamine 44-52 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 15-21 11353758-6 2001 CYP2B6 had the lowest K(m) value for the N-demethylation of (R)- and (S)-ketamine (74 and 44 microM, respectively). Ketamine 69-81 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 0-6 33599403-2 2021 Drugs metabolized mainly by CYP2B6 include artemisinin, bupropion, cyclophosphamide, efavirenz, ketamine, and methadone. Ketamine 96-104 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 28-34 31772310-6 2020 We demonstrate that IV ketamine can be transitioned to oral regimen to shorten length of stay in the intensive care unit and hospital and has future CYP2B6 pharmacogenomic considerations for further dose individualization. Ketamine 23-31 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 149-155 30906561-8 2019 Furthermore, metabolism of common CYP2B6 probe substrates, methadone and ketamine, is not detected in the presence of brain microsomes. Ketamine 73-81 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 34-40 12065445-0 2002 Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes. Ketamine 74-82 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 24-30 12065445-7 2002 N-demethylation of ketamine was correlated with nifedipine oxidase activity (CYP3A4-specific marker reaction), and it was also correlated with S-mephenytoin N-demethylase activity (CYP2B6-specific marker reaction). Ketamine 19-27 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 181-187 12065445-9 2002 In human lymphoblast-expressed P450, the activities of CYP2B6 were higher than those of CYP3A4 and CYP2C9 at three concentrations of ketamine, 0.005, 0.05, and 0.5 mM. Ketamine 133-141 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 55-61 30589555-7 2019 This investigation evaluated halogen substitution effects on CYP2B6-catalyzed ketamine analogs N-demethylation in vitro and modeled interactions with CYP2B6 using various computational approaches. Ketamine 78-86 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 61-67 30589555-16 2019 The binding pocket of CYP2B6 also suggested a hydrophobic component to substrate docking, on the basis of a strong linear correlation ( R2 = 0.92) between lipophilicity ( Alog P) and metabolism (log Km) of ketamine and analogs. Ketamine 206-214 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 22-28