PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 26910068-0 2016 In Vitro Approaches to Study Regulation of Hepatic Cytochrome P450 (CYP) 3A Expression by Paclitaxel and Rifampicin. Paclitaxel 90-100 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 51-75 26910068-4 2016 In this investigation, we tested the hypothesis that induction of cytochrome P450 (Cyp)3a11 gene by paclitaxel is downregulated by the inflammatory mediator, lipopolysaccharide (LPS), and that the pro-inflammatory cytokine, tumor necrosis factor (TNF)-alpha, attenuates human CYP3A4 gene induction by rifampicin. Paclitaxel 100-110 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 276-282 26910068-7 2016 Induction and subsequent downregulation of CYP3A enzyme can impact paclitaxel treatment in cancer patients where inflammatory mediators are activated. Paclitaxel 67-77 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 43-48 26211584-4 2015 We have used Schrodinger suite 2014, to perform molecular docking of human CYP3A4, by Induced Fit Docking using gemcitabine, cisplatin, carboplatin, docetaxel and paclitaxel drugs. Paclitaxel 163-173 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-81 25424246-5 2015 When using HL60, losartan and the CYP3A4-selective inhibitors, erythromycin and ketoconazole, caused a greater inhibition of the paclitaxel metabolism than quercetin, a CYP2C8-selective inhibitor. Paclitaxel 129-139 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 25398452-0 2015 Whole-exome sequencing reveals defective CYP3A4 variants predictive of paclitaxel dose-limiting neuropathy. Paclitaxel 71-81 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-47 25424246-6 2015 This demonstrated that the paclitaxel metabolism was mainly catalysed by CYP3A4 in HL60. Paclitaxel 27-37 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 73-79 25424246-7 2015 There were no significant differences found for the inhibitory effects caused by the four inhibitors of the paclitaxel metabolism in HL54, indicating that both CYP2C8 and CYP3A4 play important roles in paclitaxel metabolism in HL54. Paclitaxel 202-212 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 171-177 25424246-10 2015 The CYP2C8*3 allele carriers are likely susceptible to the interactions of losartan and CYP3A4 inhibitors to paclitaxel metabolism. Paclitaxel 109-119 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 88-94 25398452-9 2015 Relative to CYP3A4 wild-type patients, those carrying CYP3A4 defective variants had more severe neuropathy (2- and 1.3-fold higher risk of neuropathy for loss-of-function and missense variants, respectively, P = 0.045) and higher probability of neuropathy-induced paclitaxel treatment modifications (7- and 3-fold higher risk for loss-of-function and missense variants, respectively, P = 5.9 x 10(-5)). Paclitaxel 264-274 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 54-60 25398452-11 2015 CYP3A4 defective variants may provide a basis for paclitaxel treatment individualization. Paclitaxel 50-60 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 23090875-13 2013 Mouse liver microsomes metabolized paclitaxel far less efficiently than human or CYP3A4-transgenic liver microsomes, revealing much lower efficiency of paclitaxel metabolism by mouse than by human CYP3As. Paclitaxel 152-162 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 81-87 24800949-11 2014 Coadministration of pazopanib and lapatinib, weak inhibitors of CYP2C8 and CYP3A4, had an inhibitory effect on paclitaxel clearance. Paclitaxel 111-121 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-81 24637579-5 2014 The metabolism of paclitaxel is mediated primarily by the P450 cytochrome enzymes CYP2C8 and CYP3A, whereas docetaxel is only metabolized by CYP3A4. Paclitaxel 18-28 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 93-98 24476576-2 2014 Because paclitaxel is metabolized by CYP2C8 and CYP3A4, the possibility of drug-drug interactions mediated by enzyme inhibition may exist between the combining agents. Paclitaxel 8-18 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 48-54 24476576-9 2014 The present results suggest that potent and pathway-dependent inhibition of CYP2C8 and/or CYP3A4 pathways by kinase inhibitors may alter the ratio of paclitaxel metabolites in vivo, and that such changes can be clinically relevant as differential metabolism has been linked to paclitaxel-induced neurotoxicity in cancer patients. Paclitaxel 150-160 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 90-96 24476576-9 2014 The present results suggest that potent and pathway-dependent inhibition of CYP2C8 and/or CYP3A4 pathways by kinase inhibitors may alter the ratio of paclitaxel metabolites in vivo, and that such changes can be clinically relevant as differential metabolism has been linked to paclitaxel-induced neurotoxicity in cancer patients. Paclitaxel 277-287 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 90-96 23936594-1 2013 CYP3A4 is a key enzyme involved in the metabolism of numerous compounds, such as paclitaxel, and its activity shows an extensive inter-individual variation which can influence treatment response. Paclitaxel 81-91 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 23936594-2 2013 The study"s purpose was to investigate the potential predictive role of a CYP3A4 profile (CYP3A4*1B, rs2740574 and CYP3A4*22, rs35599367) in serous ovarian cancer patients treated with first-line chemotherapy (paclitaxel and cisplatin or carboplatin), after cytoreductive surgery. Paclitaxel 210-220 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 74-80 23090875-14 2013 Accordingly, ritonavir could enhance the oral bioavailability of paclitaxel in CYP3A4-humanized mice, despite the fact that these mice are P-gp-proficient. Paclitaxel 65-75 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 79-85 23090875-15 2013 Our results show that CYP3A4 inhibition most likely underlies the boosting effect of ritonavir on oral paclitaxel bioavailability in humans. Paclitaxel 103-113 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 22-28 23640974-0 2013 CYP3A4*22 genotype and systemic exposure affect paclitaxel-induced neurotoxicity. Paclitaxel 48-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 23640974-6 2013 Genetic variants of paclitaxel pharmacokinetics tested were CYP3A4*22, CYP2C8*3, CYP2C8*4, and ABCB1 3435 C>T. The association between CYP3A4*22 and neurotoxicity observed in the exploratory cohort was validated in an independent patient cohort (n = 239). Paclitaxel 20-30 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 60-66 23640974-6 2013 Genetic variants of paclitaxel pharmacokinetics tested were CYP3A4*22, CYP2C8*3, CYP2C8*4, and ABCB1 3435 C>T. The association between CYP3A4*22 and neurotoxicity observed in the exploratory cohort was validated in an independent patient cohort (n = 239). Paclitaxel 20-30 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 138-144 23640974-13 2013 In this study, female CYP3A4*22 carriers had increased risk of developing severe neurotoxicity during paclitaxel therapy. Paclitaxel 102-112 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 22-28 23090875-16 2013 Furthermore, CYP3A4-humanized mice allow improved understanding of CYP3A4-mediated paclitaxel metabolism in humans. Paclitaxel 83-93 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 13-19 23090875-16 2013 Furthermore, CYP3A4-humanized mice allow improved understanding of CYP3A4-mediated paclitaxel metabolism in humans. Paclitaxel 83-93 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 67-73 22764771-5 2012 Important examples include ketoconazole inhibition of hepatic CYP3A4 in order to increase systemic exposure to docetaxel, irinotecan and etoposide, and cyclosporine inhibition of intestinal ATP-binding cassette transporters in order to decrease the toxicity of irinotecan and increase the bioavailability of oral docetaxel, paclitaxel and topotecan. Paclitaxel 324-334 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-68 23629743-5 2013 These results are consistent with those of molecular docking simulations, where paclitaxel could not access the CYP2C8 catalytic site in the presence of nilotinib, but the binding of midazolam, a substrate of CYP3A4, to the catalytic site of CYP3A4 was not affected by nilotinib. Paclitaxel 80-90 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 209-215 23629743-5 2013 These results are consistent with those of molecular docking simulations, where paclitaxel could not access the CYP2C8 catalytic site in the presence of nilotinib, but the binding of midazolam, a substrate of CYP3A4, to the catalytic site of CYP3A4 was not affected by nilotinib. Paclitaxel 80-90 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 242-248 22680343-7 2012 AIMS: To evaluate the use of rosiglitazone and the erythromycin breath test (ERMBT), as probes of CYP2C8 and CYP3A4, respectively, to explain inter-individual variability in paclitaxel exposure. Paclitaxel 174-184 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 109-115 20212519-4 2011 We selected 13 relevant polymorphisms in genes encoding paclitaxel metabolizing enzymes (CYP2C8, CYP3A4 and CYP3A5) and transporters (organic anion transporting polypeptide (OATP) 1B1, OATP1B3 and P-glycoprotein) and genotyped them in 118 Spanish cancer patients treated with paclitaxel. Paclitaxel 56-66 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 97-103 21327421-2 2011 Paclitaxel is metabolized in the liver by CYP2C8 and CYP3A4 and transported by P-glycoprotein. Paclitaxel 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-59 22966274-3 2010 The purpose of this study was to evaluate the possible relationship between paclitaxel-induced neurotoxicity and the distribution of genetic variations with reported functional significance in the ABCB1, CYP2C8 and CYP3A4 genes that are all implicated in taxol metabolism. Paclitaxel 76-86 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 215-221 21056987-2 2011 This information may be important for understanding paclitaxel metabolism in vivo and in the investigation of the role of genetic polymorphisms in the metabolizing enzymes CYP2C8 and CYP3A4/CYP3A5 and the ABCB1 transporter. Paclitaxel 52-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 183-189 20847137-3 2010 In this study, catalytic activities of the two alleles found in East Asians, CYP3A4*16 (T185S) and CYP3A4*18 (L293P), were assessed using the following seven substrates: midazolam, carbamazepine, atorvastatin, paclitaxel, docetaxel, irinotecan, and terfenadine. Paclitaxel 210-220 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 77-83 20847137-3 2010 In this study, catalytic activities of the two alleles found in East Asians, CYP3A4*16 (T185S) and CYP3A4*18 (L293P), were assessed using the following seven substrates: midazolam, carbamazepine, atorvastatin, paclitaxel, docetaxel, irinotecan, and terfenadine. Paclitaxel 210-220 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 99-105 20847137-5 2010 CYP3A4.16 exhibited intrinsic clearances (V(max)/K(m)) that were lowered considerably (by 84-60%) for metabolism of midazolam, carbamazepine, atorvastatin, paclitaxel, and irinotecan compared with CYP3A4.1 due to increased K(m) with or without decreased V(max) values, whereas no apparent decrease in intrinsic clearance was observed for docetaxel. Paclitaxel 156-166 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 20847137-6 2010 On the other hand, K(m) values for CYP3A4.18 were comparable to those for CYP3A4.1 for all substrates except terfenadine; but V(max) values were lower for midazolam, paclitaxel, docetaxel, and irinotecan, resulting in partially reduced intrinsic clearance values (by 34-52%). Paclitaxel 166-176 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 35-41 20847137-6 2010 On the other hand, K(m) values for CYP3A4.18 were comparable to those for CYP3A4.1 for all substrates except terfenadine; but V(max) values were lower for midazolam, paclitaxel, docetaxel, and irinotecan, resulting in partially reduced intrinsic clearance values (by 34-52%). Paclitaxel 166-176 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 74-80 20977456-8 2010 KEY RESULTS: N-desmethylimatinib formation was correlated with microsomal oxidation of the CYP3A4 substrates testosterone (rho= 0.60; P < 0.01) and midazolam (rho= 0.46; P < 0.05), and the CYP2C8 substrate paclitaxel (rho= 0.58; P < 0.01). Paclitaxel 212-222 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 91-97 20814160-3 2010 Hydroxylation activities of mfCYP3A4 and mfCYP3A5 toward coumarin, paclitaxel, diclofenac, flurbiprofen, and S-mephenytoin were below detectable levels, as was also true for CYP3A4 and CYP3A5. Paclitaxel 67-77 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-36 22966274-3 2010 The purpose of this study was to evaluate the possible relationship between paclitaxel-induced neurotoxicity and the distribution of genetic variations with reported functional significance in the ABCB1, CYP2C8 and CYP3A4 genes that are all implicated in taxol metabolism. Paclitaxel 255-260 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 215-221 18039807-6 2008 Compared with paclitaxel, the major hydroxylation site transferred from C6alpha to C4"", and the main metabolizing P450 changed from CYP2C8 to CYP3A4 for cephalomannine. Paclitaxel 14-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 143-149 18839173-2 2009 In addition to rifampicin and hyperforin, the anticancer drug paclitaxel has also been shown to be an inducer of CYP3A4 via activation of the pregnane X receptor (PXR). Paclitaxel 62-72 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 113-119 18839173-7 2009 RESULTS: Paclitaxel, erlotinib, tamoxifen, ifosfamide, flutamide and docetaxel are able to activate PXR, while only strong PXR activation leads to significant induction of CYP3A4 activity. Paclitaxel 9-19 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 172-178 17992531-3 2008 In paclitaxel-administered cancer patients, an association of CYP3A4*16B harboring the low activity allele *16 [554C > G (Thr185Ser)] has been shown with altered metabolite/paclitaxel area under the plasma concentration-time curve (AUC) ratios, suggesting a possible impact of *16B on the PK of other drugs. Paclitaxel 3-13 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-68 17992531-3 2008 In paclitaxel-administered cancer patients, an association of CYP3A4*16B harboring the low activity allele *16 [554C > G (Thr185Ser)] has been shown with altered metabolite/paclitaxel area under the plasma concentration-time curve (AUC) ratios, suggesting a possible impact of *16B on the PK of other drugs. Paclitaxel 176-186 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-68 19143748-1 2009 The purpose of this study was to evaluate the role of sequence variants in the CYP2C8, ABCB1 and CYP3A4 genes and the CYP3A4 phenotype for the pharmacokinetics and toxicity of paclitaxel in ovarian cancer patients. Paclitaxel 176-186 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 97-103 19143748-1 2009 The purpose of this study was to evaluate the role of sequence variants in the CYP2C8, ABCB1 and CYP3A4 genes and the CYP3A4 phenotype for the pharmacokinetics and toxicity of paclitaxel in ovarian cancer patients. Paclitaxel 176-186 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 118-124 17906456-7 2007 A haplotype of CYP3A4 was associated with paclitaxel pharmacokinetics. Paclitaxel 42-52 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 15-21 17267149-1 2007 As many anticancer agents paclitaxel is a substrate for ATP-binding cassette (ABC) transporters such as P-glycoprotein-mediated efflux, and its metabolism in humans mainly catalyzed by CYP 3A4 and 2C8. Paclitaxel 26-36 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 185-200 17701008-4 2007 The effects of patient characteristics, including single-nucleotide polymorphisms of MDR1(ABCB1), CYP2C8, CYP3A4, and CYP3A5, on the total body clearance of paclitaxel were evaluated. Paclitaxel 157-167 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 106-112 16299241-0 2005 Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1 polymorphisms with the pharmacokinetics of paclitaxel. Paclitaxel 92-102 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 23-29 16890579-0 2006 Impact of the haplotype CYP3A4*16B harboring the Thr185Ser substitution on paclitaxel metabolism in Japanese patients with cancer. Paclitaxel 75-85 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 24-30 16890579-2 2006 We investigated the association between CYP3A4 haplotypes and pharmacokinetic parameters of paclitaxel metabolism. Paclitaxel 92-102 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-46 16708050-10 2006 CYP3A4 conferred resistance to taxol, vinblastine and topotecan. Paclitaxel 31-36 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 16299241-1 2005 PURPOSE: To retrospectively evaluate the effects of six known allelic variants in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes on the pharmacokinetics of the anticancer agent paclitaxel (Taxol). Paclitaxel 174-184 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 94-100 17399990-8 2007 Interestingly, in vitro biotransformation studies of compounds 4 and 5 using human CYP-450 isoforms revealed, that conversely to XR9576, compounds 4 and 5 inhibited CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to tumor cell chemoresistance by enhancing the biodisposition of numerous drugs, notably paclitaxel. Paclitaxel 332-342 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 165-171 16904325-6 2006 In addition, in vitro metabolism studies of 23a with a subset of human CYP-450 isoforms revealed that, unlike XR9576, 23a inhibited CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to tumor cell chemoresistance by enhancing the biodisposition of anticancer drugs such as paclitaxel toward metabolism. Paclitaxel 300-310 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 132-138 16753005-1 2006 INTRODUCTION: We have previously shown that human colorectal cancer tissue is able to inactivate the anticancer drug paclitaxel through cytochrome P450 (CYP)2C8 and CYP3A4 metabolisms. Paclitaxel 117-127 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 165-171 16144941-5 2005 RESULTS: The current study showed that paclitaxel, discodermolide, and an analogue of epothilone B, BMS-247550, induced CYP3A4 protein expression in HepG2 hepatoma cells. Paclitaxel 39-49 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 120-126 15856231-3 2005 Recent studies in vitro have shown that paclitaxel treatment increases the level of CYP2C8 and CYP3A4 in human hepatocytes as well as PGP in colon tumor cells. Paclitaxel 40-50 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 95-101 15856231-8 2005 The effect of paclitaxel treatment on hepatic expression of PGP and P450 isoforms (CYP2C and CYP3A) was determined to elucidate the mechanism by which paclitaxel disposition is altered by previous drug exposure. Paclitaxel 14-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 93-98 15856231-8 2005 The effect of paclitaxel treatment on hepatic expression of PGP and P450 isoforms (CYP2C and CYP3A) was determined to elucidate the mechanism by which paclitaxel disposition is altered by previous drug exposure. Paclitaxel 151-161 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 93-98 15650019-5 2005 In contrast, the anticancer agents, cisplatin and paclitaxel, strongly activated PXR-mediated transcription through the MDR1-responsive element compared with the CYP3A4-responsive element, whereas these drugs also enhanced the MDR1 expression compared with the CYP3A4 expression. Paclitaxel 50-60 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 162-168 15650019-5 2005 In contrast, the anticancer agents, cisplatin and paclitaxel, strongly activated PXR-mediated transcription through the MDR1-responsive element compared with the CYP3A4-responsive element, whereas these drugs also enhanced the MDR1 expression compared with the CYP3A4 expression. Paclitaxel 50-60 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 261-267 15304522-7 2004 Simultaneous inactivation of CYP2C8 and CYP3A4 (paclitaxel 3"-phenyl-hydroxylation) was observed using amiodarone, isoniazid, and phenelzine with the efficiency of inactivation greater for the CYP3A4 pathway. Paclitaxel 48-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-46 15655291-0 2005 Utilization of human liver microsomes to explain individual differences in paclitaxel metabolism by CYP2C8 and CYP3A4. Paclitaxel 75-85 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 111-117 15655291-2 2005 Paclitaxel is metabolized by CYP2C8 and CYP3A4, and these enzymes are known to differ between individuals, although the details have not been clarified. Paclitaxel 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-46 15655291-4 2005 We investigated the effect of the polymorphisms on paclitaxel metabolism by analyzing metabolic activities of CYP2C8 and CYP3A4 and expressions of mRNA and protein. Paclitaxel 51-61 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 121-127 15655291-9 2005 Inter-individual differences in paclitaxel metabolism may be related to CYP2C8 and CYP3A4 mRNA expression. Paclitaxel 32-42 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 83-89 15864135-6 2005 CYP3A4-luciferase reporter assays revealed that the Q158K variant gave rise to much lower levels of CYP3A4 promoter activity in LS174T and HepG2 cells exposed to the PXR ligands, rifampin and paclitaxel, than did wild-type PXR. Paclitaxel 192-202 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 15864135-6 2005 CYP3A4-luciferase reporter assays revealed that the Q158K variant gave rise to much lower levels of CYP3A4 promoter activity in LS174T and HepG2 cells exposed to the PXR ligands, rifampin and paclitaxel, than did wild-type PXR. Paclitaxel 192-202 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 100-106 15304522-7 2004 Simultaneous inactivation of CYP2C8 and CYP3A4 (paclitaxel 3"-phenyl-hydroxylation) was observed using amiodarone, isoniazid, and phenelzine with the efficiency of inactivation greater for the CYP3A4 pathway. Paclitaxel 48-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 193-199 14512701-1 2003 Taxol treatment froze the cell cycle in the G(2)/M phase, induced morphological changes characteristic of apoptotic/necrotic cell death and increased CYP3A4 enzymatic activity, CYP3A4 mRNA and protein levels in HepG2 cells overexpressing CYP3A4. Paclitaxel 0-5 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 150-156 15175893-9 2004 A comparison of the cellular concentrations of paclitaxel and docetaxel, in the cell culture models employed for evaluating CYP3A4 induction and hPXR activation, revealed that the intracellular paclitaxel levels were three-fold higher than that of docetaxel. Paclitaxel 194-204 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 124-130 15175893-0 2004 Differences in the induction of cytochrome P450 3A4 by taxane anticancer drugs, docetaxel and paclitaxel, assessed employing primary human hepatocytes. Paclitaxel 94-104 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-51 15175893-2 2004 The aim of this study was to comparatively examine the effects of paclitaxel and docetaxel, two structurally related taxane anticancer agents, on the activity and expression of hepatic CYP3A4. Paclitaxel 66-76 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 185-191 15175893-6 2004 Furthermore, employing cell-based reporter gene assay in CV-1 cells, we evaluated the capacity of paclitaxel and docetaxel to activate human pregnane X receptor (hPXR), an orphan nuclear receptor that plays a key role in the transcriptional regulation of CYP3A4. Paclitaxel 98-108 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 255-261 15175893-7 2004 RESULTS: In concurrence with previous reports, we observed that paclitaxel potently induced CYP3A4 activity and expression in hepatocytes treated for 48-96 h. However, docetaxel did not increase the activity or the CYP3A4 immunoreactive protein levels for treatment periods up to 96 h. A marginal increase in the CYP3A4 mRNA levels was observed in cells treated with higher levels (5 and 10 microM) of docetaxel. Paclitaxel 64-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 92-98 15175893-7 2004 RESULTS: In concurrence with previous reports, we observed that paclitaxel potently induced CYP3A4 activity and expression in hepatocytes treated for 48-96 h. However, docetaxel did not increase the activity or the CYP3A4 immunoreactive protein levels for treatment periods up to 96 h. A marginal increase in the CYP3A4 mRNA levels was observed in cells treated with higher levels (5 and 10 microM) of docetaxel. Paclitaxel 64-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 215-221 15175893-7 2004 RESULTS: In concurrence with previous reports, we observed that paclitaxel potently induced CYP3A4 activity and expression in hepatocytes treated for 48-96 h. However, docetaxel did not increase the activity or the CYP3A4 immunoreactive protein levels for treatment periods up to 96 h. A marginal increase in the CYP3A4 mRNA levels was observed in cells treated with higher levels (5 and 10 microM) of docetaxel. Paclitaxel 64-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 215-221 15175893-9 2004 A comparison of the cellular concentrations of paclitaxel and docetaxel, in the cell culture models employed for evaluating CYP3A4 induction and hPXR activation, revealed that the intracellular paclitaxel levels were three-fold higher than that of docetaxel. Paclitaxel 47-57 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 124-130 14512701-1 2003 Taxol treatment froze the cell cycle in the G(2)/M phase, induced morphological changes characteristic of apoptotic/necrotic cell death and increased CYP3A4 enzymatic activity, CYP3A4 mRNA and protein levels in HepG2 cells overexpressing CYP3A4. Paclitaxel 0-5 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 177-183 14512701-1 2003 Taxol treatment froze the cell cycle in the G(2)/M phase, induced morphological changes characteristic of apoptotic/necrotic cell death and increased CYP3A4 enzymatic activity, CYP3A4 mRNA and protein levels in HepG2 cells overexpressing CYP3A4. Paclitaxel 0-5 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 177-183 14512701-4 2003 Preincubation of cells with an anti-MDR1 monoclonal antibody prior to the drug treatment, coincubation of cells with a potent CYP3A4 inhibitor--ketoconazole--or with both compounds increased Taxol toxicity and proapoptotic activity, indicating that the P-glycoprotein system has a major role in Taxol disposition in hepatoblastoma cells. Paclitaxel 191-196 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 126-132 14512701-4 2003 Preincubation of cells with an anti-MDR1 monoclonal antibody prior to the drug treatment, coincubation of cells with a potent CYP3A4 inhibitor--ketoconazole--or with both compounds increased Taxol toxicity and proapoptotic activity, indicating that the P-glycoprotein system has a major role in Taxol disposition in hepatoblastoma cells. Paclitaxel 295-300 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 126-132 14522368-7 2003 Cytochrome P450 3A4 inducing anti-epileptic drugs like phenytoin, carbamazepine and phenobarbital may significantly increase the metabolism of many chemotherapeutic agents like CPT11 and paclitaxel (but also of newer biological agents like many tyrosine kinase inhibitors). Paclitaxel 187-197 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-19 11901098-2 2002 In spite of their close chemical structure, the two drugs are oxidized by two different enzymes; CYP2C8 catalyzes the 6-hydroxylation on the taxane ring of paclitaxel, whereas CYP3A4 oxidizes docetaxel on the tert-butyl group of the lateral chain in C13. Paclitaxel 156-166 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 176-182 12237780-0 2002 Expression of paclitaxel-inactivating CYP3A activity in human colorectal cancer: implications for drug therapy. Paclitaxel 14-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-43 10421615-5 1999 The maximal CYP3A activity detected after treatment with Taxol or rifampicin was similar in six separate human hepatocyte cultures, suggesting that the cultures have achieved a limit of maximally inducible CYP3A. Paclitaxel 57-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 12-17 12064370-4 2002 Using human liver microsomes, we have demonstrated that OC144-093 inhibited the CYP3A mediated metabolism of paclitaxel at high concentrations only (Ki = 39.8 +/- 5.1 microM, n=3). Paclitaxel 109-119 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 80-85 11914905-7 2002 The inhibitory concentrations of paclitaxel, tamoxifen and cyclosporine on MMDx metabolism were in the range of those observed in patients upon administration of these drugs, which are known to be CYP3A4 substrates. Paclitaxel 33-43 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 197-203 9675018-0 1998 Induction of cytochrome P4503A by taxol in primary cultures of human hepatocytes. Paclitaxel 34-39 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 13-19 10421615-1 1999 We have previously reported that paclitaxel (Taxol) is a potent inducer of cytochrome P-450 (CYP) 3A protein and CYP3A mRNA in human hepatocyte cultures. Paclitaxel 33-43 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-100 10421615-1 1999 We have previously reported that paclitaxel (Taxol) is a potent inducer of cytochrome P-450 (CYP) 3A protein and CYP3A mRNA in human hepatocyte cultures. Paclitaxel 33-43 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 113-118 10421615-1 1999 We have previously reported that paclitaxel (Taxol) is a potent inducer of cytochrome P-450 (CYP) 3A protein and CYP3A mRNA in human hepatocyte cultures. Paclitaxel 45-50 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-100 10421615-1 1999 We have previously reported that paclitaxel (Taxol) is a potent inducer of cytochrome P-450 (CYP) 3A protein and CYP3A mRNA in human hepatocyte cultures. Paclitaxel 45-50 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 113-118 10421615-2 1999 Here we report that Taxol increased CYP3A-dependent testosterone 6beta-hydroxylation in intact hepatocytes. Paclitaxel 20-25 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 36-41 10421615-4 1999 Treatment of hepatocyte cultures with concentrations of Taxol higher than 10 microM caused a dose-dependent decrease in testosterone 6beta-hydroxylase activity, amount of CYP3A protein, and total protein synthesis. Paclitaxel 56-61 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 171-176 9675018-1 1998 In primary cultures of human hepatocytes, paclitaxel (Taxol), at pharmacological concentrations, was demonstrated to induce immunoreactive cytochrome P4503A (CYP3A). Paclitaxel 42-52 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 139-145 9675018-1 1998 In primary cultures of human hepatocytes, paclitaxel (Taxol), at pharmacological concentrations, was demonstrated to induce immunoreactive cytochrome P4503A (CYP3A). Paclitaxel 42-52 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 158-163 9675018-1 1998 In primary cultures of human hepatocytes, paclitaxel (Taxol), at pharmacological concentrations, was demonstrated to induce immunoreactive cytochrome P4503A (CYP3A). Paclitaxel 54-59 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 139-145 9675018-1 1998 In primary cultures of human hepatocytes, paclitaxel (Taxol), at pharmacological concentrations, was demonstrated to induce immunoreactive cytochrome P4503A (CYP3A). Paclitaxel 54-59 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 158-163 9675018-3 1998 In general, exposure to increasing concentrations of Taxol (0.2 to 10 microM) resulted in increases in immunoreactive CYP3A. Paclitaxel 53-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 118-123 9675018-4 1998 In four of the cultures, treatment of hepatocytes with the lowest concentration of Taxol tested (0.2 microM) resulted in approximately two-fold increases in CYP3A. Paclitaxel 83-88 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 157-162 9675018-6 1998 Taxol was almost as effective as rifampicin in inducing CYP3A in two of the cultures, but less effective than rifampicin in two other cultures. Paclitaxel 0-5 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-61 9675018-7 1998 CYP3A4 mRNA was increased by Taxol. Paclitaxel 29-34 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 9675018-9 1998 These results demonstrate that Taxol is a potent inducer of CYP3A in human hepatocytes. Paclitaxel 31-36 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 60-65 9492385-0 1998 Modification of paclitaxel metabolism in a cancer patient by induction of cytochrome P450 3A4. Paclitaxel 16-26 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 74-93 9492385-7 1998 A high CYP3A4 activity in the patient is consistent with the repeated administration of methylprednisolone for 14 days before paclitaxel treatment, a compound known to induce the CYP3A isoform, and with the increased ratio of 6beta-hydroxycortisol/cortisol in urine, an index of CYP3A activity. Paclitaxel 126-136 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 7-13 9492385-7 1998 A high CYP3A4 activity in the patient is consistent with the repeated administration of methylprednisolone for 14 days before paclitaxel treatment, a compound known to induce the CYP3A isoform, and with the increased ratio of 6beta-hydroxycortisol/cortisol in urine, an index of CYP3A activity. Paclitaxel 126-136 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 7-12 7473140-8 1995 Inhibitor experiments suggest that typical CYP3A substrates/inhibitors (e.g., cyclosporin, epipodophyllotoxins) may significantly interact with paclitaxel in vivo. Paclitaxel 144-154 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 43-48 8703657-6 1995 In particular, enzymes of the CYP3A subfamily play a role in the metabolism of many anticancer drugs, including epipodophyllotoxins, ifosphamide, tamoxifen, taxol and vinca alkaloids. Paclitaxel 157-162 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-35 33649523-5 2021 The heterozygous genotype of CYP3A4*22 showed a trend of association with skin reactions in pts treated with paclitaxel and nab-paclitaxel (RR = 6.92; 95% CI 0.47, 99.8; p = 0.0766). Paclitaxel 109-119 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 29-35 7834963-5 1994 Cytochrome P450 enzymes of the CYP3A and CYP2C subfamilies appear to be involved in hepatic metabolism of paclitaxel. Paclitaxel 106-116 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 31-36 34304352-3 2022 Paclitaxel is predominantly metabolized in the liver by cytochrome P450 (CYP) 2C8 to produce 6alpha-hydroxypaclitaxel and by CYP3A4 to produce 3"-p-hydroxypaclitaxel. Paclitaxel 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 125-131 34304352-4 2022 In this study, we evaluated the inhibitory or inducing effects of goshajinkigan extract (GJG) and its representative and bioavailable constituents, geniposidic acid, plantagoguanidinic acid, paeoniflorin, catalpol, loganin, and neoline, on the metabolism of paclitaxel via CYP2C8 and CYP3A4 using pooled human liver microsomes and cultured human cryopreserved hepatocytes to provide the drug information about the pharmacokinetic interaction of this combination therapy. Paclitaxel 258-268 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 284-290 33446524-6 2021 Moreover, the hydroxylation of paclitaxel was evaluated using recombinant CYP3A4 and CYP3A5. Paclitaxel 31-41 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 74-80 7913410-0 1994 Metabolism of taxol by human hepatic microsomes and liver slices: participation of cytochrome P450 3A4 and an unknown P450 enzyme. Paclitaxel 14-19 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 83-102 8791772-0 1996 Assays of CYP2C8- and CYP3A4-mediated metabolism of taxol in vivo and in vitro. Paclitaxel 52-57 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 22-28 34097831-0 2021 Carbon Monoxide Inhibits Cytochrome P450 Enzymes CYP3A4/2C8 in Human Breast Cancer Cells, Increasing Sensitivity to Paclitaxel. Paclitaxel 116-126 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 49-59 34097831-2 2021 Cytochrome P450 enzymes CYP3A4 and CYP2C8, which metabolically inactivate PTX in hepatic tissue, are overexpressed in malignant breast tissues. Paclitaxel 74-77 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 24-30 34097831-3 2021 CYP3A4 expression correlates with PTX therapy failure and poor outcomes, though no direct evidence of CYP3A4 contributing to PTX sensitivity exists. Paclitaxel 34-37 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 34097831-5 2021 Using a photo-activated CO-releasing molecule, we have assessed the ability of CO to alter the pharmacokinetics of PTX in breast cancer cells via inhibition of CYP3A4/2C8 and determined that CO does enhance sensitivity of breast cancer cells to PTX. Paclitaxel 115-118 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 160-170 34097831-6 2021 Inhibition of CYP3A4/2C8 by CO could therefore be a promising therapeutic strategy to enhance PTX response in breast cancer. Paclitaxel 94-97 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 14-24 33649523-9 2021 Despite the population was heterogeneous, CYP3A4*22 and CYP2C8 SNPs may influence paclitaxel and nab-paclitaxel toxicity and ABCB1 c.3435 may affect taxanes effectiveness, even if any statistically significant was found. Paclitaxel 101-111 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 42-48 33649523-5 2021 The heterozygous genotype of CYP3A4*22 showed a trend of association with skin reactions in pts treated with paclitaxel and nab-paclitaxel (RR = 6.92; 95% CI 0.47, 99.8; p = 0.0766). Paclitaxel 128-138 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 29-35 33649523-9 2021 Despite the population was heterogeneous, CYP3A4*22 and CYP2C8 SNPs may influence paclitaxel and nab-paclitaxel toxicity and ABCB1 c.3435 may affect taxanes effectiveness, even if any statistically significant was found. Paclitaxel 82-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 42-48 32505840-12 2020 The synergetic effect was played by Xiaoaiping injection inhibiting paclitaxel-induced PXR and CAR expression, which subsequently inhibited CYP450 enzymes CYP2C8 and CYP3A4, transporter P-gp and anti-apoptotic proteins Bcl-2 and Bcl-xl in SK-OV-3 cells. Paclitaxel 68-78 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 166-172 33513992-6 2021 The addition of RTV can inhibit the P-gp and CYP3A4-mediated metabolism of PTX, thus aiding in reversing MDR and sensitizing the cells toward PTX. Paclitaxel 75-78 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 45-51 33513992-6 2021 The addition of RTV can inhibit the P-gp and CYP3A4-mediated metabolism of PTX, thus aiding in reversing MDR and sensitizing the cells toward PTX. Paclitaxel 142-145 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 45-51 33491578-6 2021 CYP3A4 liver enzymes are responsible for the metabolism of fifty percent of the drugs and are major metabolizing enzyme for paclitaxel. Paclitaxel 124-134 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 32364081-0 2020 Paclitaxel Nanoparticles Induce Apoptosis and Regulate TXR1, CYP3A4 and CYP2C8 in Breast Cancer and Hepatoma Cells. Paclitaxel 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-67 30840584-3 2019 We also examined the effects of pretreatment with menthol on the cytotoxic activity of paclitaxel (PAC) and vincristine (VIN), which are substrates of CYP3A4, in the cells. Paclitaxel 87-97 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 151-157 29251928-5 2018 Selected compounds were shown to reverse paclitaxel resistance in HEK293 cells overexpressing P-gp and were selective toward P-gp over CYP3A4. Paclitaxel 41-51 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 135-141 27599706-4 2017 METHODS: This study predicted the magnitude of the DDI between efavirenz, an inducer of CYP3A4 and inhibitor of CYP2C8, and dual CYP3A4/CYP2C8 substrates (repaglinide, montelukast, pioglitazone, paclitaxel) using a physiologically based pharmacokinetic (PBPK) modeling approach integrating concurrent effects on CYPs. Paclitaxel 195-205 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 129-135 29054579-0 2018 Relevance of the CYP3A4*20 variant as a predictor of paclitaxel-induced neuropathy in the Spanish population. Paclitaxel 53-63 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 17-23 27572875-4 2016 PXR agonists, phthalate and pregnenolone had significant positive effects on cytochrome P450 (CYP) 3A4 expression and PXR-mediated transcription through the CYP3A4 promoter, whereas MDR1 expression and PXR-mediated transcription though the MDR1 promoter were significantly increased in the presence of paclitaxel or cisplatin. Paclitaxel 302-312 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 157-163 27574448-0 2016 Polymorphism of CYP3A4 and ABCB1 genes increase the risk of neuropathy in breast cancer patients treated with paclitaxel and docetaxel. Paclitaxel 110-120 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-22