PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 32778670-3 2020 Thus, the aim of this study was to assess the allele and genotype frequencies and the relationship between CYP3A4/5, DPYD, UGT1A1, ABCB1, and ABCC2 genetic variations and irinotecan-induced toxicity in Thai colorectal cancer patients. Irinotecan 171-181 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 107-115 33619631-0 2021 Effect of UGT1A1, CYP3A and CES Activities on the Pharmacokinetics of Irinotecan and its Metabolites in Patients with UGT1A1 Gene Polymorphisms. Irinotecan 70-80 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 18-23 33619631-4 2021 CPT-11 is also converted to 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin (APC) and 7-ethyl-10-(4-amino-1-piperidino) carbonyloxycamptothecin (NPC) by cytochrome P450 3A (CYP3A), and this route also affects the plasma concentration of SN-38. Irinotecan 0-6 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 182-200 33619631-4 2021 CPT-11 is also converted to 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin (APC) and 7-ethyl-10-(4-amino-1-piperidino) carbonyloxycamptothecin (NPC) by cytochrome P450 3A (CYP3A), and this route also affects the plasma concentration of SN-38. Irinotecan 0-6 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 202-207 33619631-14 2021 Patient 3 had the lowest AUC of SN-38, caused by a lower level of CES activity and increased CYP3A activity. Irinotecan 32-37 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 93-98 33619631-15 2021 CONCLUSION: In this study, we indicated that the plasma AUC of SN-38 and AUC ratio of SN-38G/SN-38 may depend on changes in the activities of CYP3A, CES, and UGT1A1. Irinotecan 63-68 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 142-147 33619631-15 2021 CONCLUSION: In this study, we indicated that the plasma AUC of SN-38 and AUC ratio of SN-38G/SN-38 may depend on changes in the activities of CYP3A, CES, and UGT1A1. Irinotecan 86-91 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 142-147 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. Irinotecan 122-132 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-68 23394826-14 2013 In clinical studies using midazolam or anticancer drugs (irinotecan and imatinib) as known CYP3A4 substrates in combination with SJW, decreased plasma levels of these drugs were observed, which was expected as a consequence of CYP3A4 induction. Irinotecan 57-67 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 91-97 23394826-14 2013 In clinical studies using midazolam or anticancer drugs (irinotecan and imatinib) as known CYP3A4 substrates in combination with SJW, decreased plasma levels of these drugs were observed, which was expected as a consequence of CYP3A4 induction. Irinotecan 57-67 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 227-233 29504153-0 2018 Relevance of CYP3A4*20, UGT1A1*37 and UGT1A1*28 variants in irinotecan-induced severe toxicity. Irinotecan 60-70 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 13-19 29504153-3 2018 As CYP3A4 is also an irinotecan-metabolizing enzyme, our study aimed to elucidate the influence of the CYP3A4*20 loss-of-function allele in the toxicity profile of these patients. Irinotecan 21-31 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 3-9 29504153-3 2018 As CYP3A4 is also an irinotecan-metabolizing enzyme, our study aimed to elucidate the influence of the CYP3A4*20 loss-of-function allele in the toxicity profile of these patients. Irinotecan 21-31 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 103-109 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. Irinotecan 261-271 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-68 18666754-5 2006 Furthermore, the analysis of the conversion of irinotecan into SN-38 by carboxylesterase, the detoxification of irinotecan and SN-38 by CYP3A4 and UDP-glucuronosyl transferases, and the activity of excretory systems (i.e., cMOAT, P-gp and MRP) seems able to predict the interindividual variability in pharmacokinetics and pharmacodynamics, being possible to predict untolerable toxicities. Irinotecan 127-132 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 136-142 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. Irinotecan 233-243 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. Irinotecan 233-243 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. Irinotecan 172-182 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 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. Irinotecan 172-182 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 197-203 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%). Irinotecan 193-203 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 35-41 20719167-2 2009 Irinotecan, oxidized by CYP3A4 to produce inactive compounds, is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC) patients. Irinotecan 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 24-30 20719167-3 2009 CYP3A4(*)16B polymorphism was associated with decreased metabolism of irrinotecan. Irinotecan 70-81 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 17992531-7 2008 RESULTS: Area under the concentration-time curve ratios of APC/irinotecan, an in vivo parameter for CYP3A4 activity, were significantly higher in females than in males. Irinotecan 63-73 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 100-106 17992531-12 2008 CONCLUSION: This study suggested that CYP3A4*16B was associated with decreased metabolism of irinotecan to APC. Irinotecan 93-103 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-44 23631285-6 2012 The mutations in other enzyme systems also play role in the etiopathogenesis of the irinotecan toxicity: CYP3A (cytochrome P-450), ABC family of transmembrane transporters (adenosine-triphosphate binding cassette). Irinotecan 84-94 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 105-110 20716241-1 2010 WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The anticancer agent irinotecan is a prodrug that is hydrolyzed by hepatic carboxylesterase to its active and toxic metabolite SN-38 and oxidized by CYP3A4 to its inactive metabolite APC. Irinotecan 63-73 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 191-197 20716241-1 2010 WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The anticancer agent irinotecan is a prodrug that is hydrolyzed by hepatic carboxylesterase to its active and toxic metabolite SN-38 and oxidized by CYP3A4 to its inactive metabolite APC. Irinotecan 169-174 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 191-197 20716241-2 2010 Irinotecan therapy is complicated by co-administered drugs that inhibit CYP3A4 and decrease APC formation and that indirectly increase SN-38 formation. Irinotecan 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 72-78 20716241-4 2010 WHAT THIS STUDY ADDS: In microsomal fractions from patients with severe hepatic dysfunction both APC and SN-38 formation were decreased due to down-regulation of CYP3A4 and carboxylesterase enzymes. Irinotecan 105-110 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 162-168 20716241-14 2010 CONCLUSIONS: Down-regulation of CYP3A4 in liver disease decreased APC formation from irinotecan. Irinotecan 85-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-38 20716241-16 2010 However, in a subset of disease samples SN-38 production was relatively high because CYP3A4 activity was markedly impaired. Irinotecan 40-45 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 85-91 20068078-0 2010 A CYP3A4 phenotype-based dosing algorithm for individualized treatment of irinotecan. Irinotecan 74-84 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 2-8 20068078-1 2010 PURPOSE: Irinotecan, the prodrug of SN-38, is extensively metabolized by cytochrome P450-3A4 (CYP3A4). Irinotecan 9-19 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 73-92 20068078-1 2010 PURPOSE: Irinotecan, the prodrug of SN-38, is extensively metabolized by cytochrome P450-3A4 (CYP3A4). Irinotecan 9-19 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 94-100 20068078-1 2010 PURPOSE: Irinotecan, the prodrug of SN-38, is extensively metabolized by cytochrome P450-3A4 (CYP3A4). Irinotecan 36-41 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 73-92 20068078-1 2010 PURPOSE: Irinotecan, the prodrug of SN-38, is extensively metabolized by cytochrome P450-3A4 (CYP3A4). Irinotecan 36-41 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 94-100 20068078-2 2010 A randomized trial was done to assess the utility of an algorithm for individualized irinotecan dose calculation based on a priori CYP3A4 activity measurements by the midazolam clearance test. Irinotecan 85-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 131-137 20068078-11 2010 CONCLUSIONS: Incorporation of CYP3A4 phenotyping in dose calculation resulted in an improved predictability of the pharmacokinetic and toxicity profile of irinotecan, thereby lowering the incidence of severe neutropenia. Irinotecan 155-165 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-36 20068078-12 2010 In combination with UGT1A1*28 genotyping, CYP3A4 phenotype determination should be explored further as a strategy for the individualization of irinotecan treatment. Irinotecan 143-153 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 42-48 17992531-0 2008 Impact of CYP3A4 haplotypes on irinotecan pharmacokinetics in Japanese cancer patients. Irinotecan 31-41 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 10-16 17992531-1 2008 BACKGROUND AND PURPOSE: Cytochrome P450 3A4 (CYP3A4) converts an anticancer prodrug, irinotecan, to inactive metabolites such as APC. Irinotecan 85-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 24-43 17992531-1 2008 BACKGROUND AND PURPOSE: Cytochrome P450 3A4 (CYP3A4) converts an anticancer prodrug, irinotecan, to inactive metabolites such as APC. Irinotecan 85-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 45-51 17992531-2 2008 However, the contribution of CYP3A4 genetic polymorphisms to irinotecan pharmacokinetics (PK) and pharmacodynamics (PD) is not fully elucidated. Irinotecan 61-71 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 29-35 17992531-4 2008 In this study, the effects of CYP3A4 haplotypes including *16B on irinotecan PK/PD were investigated in irinotecan-administered patients. Irinotecan 66-76 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-36 17992531-5 2008 METHODS: The CYP3A4 genotypes for 177 Japanese cancer patients who received irinotecan were defined in terms of 4 major haplotypes, i.e., *1A (wild type), *1G (IVS10 + 12G > A), *16B [554C > G (Thr185Ser) and IVS10 + 12G > A], and *18B [878T > C (Leu293Pro) and IVS10 + 12G > A]. Irinotecan 76-86 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 13-19 17992531-6 2008 Associations of CYP3A4 genotypes with irinotecan PK and severe toxicities (grade 3 diarrhea and grade 3 or 4 neutropenia) were investigated. Irinotecan 38-48 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-22 18248513-6 2008 Both of naringenin and elacridar separately enhanced the sensitivity for CPT-11 and SN-38 in KYN-2 cells abundantly expressing BCRP, CYP3A4/5 and UGT1A1, but not in KYN-1 cells expressing lower levels. Irinotecan 84-89 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 133-139 16508919-5 2006 Many enzymes are involved in controlling the disposition of irinotecan, including the cellular target (TOP1), metabolism enzymes (CES2, UGT1A1, CYP3A4, CYP3A5), and cellular transporters of the anti-cancer agent (ABCB1, ABCC1, ABCC2, ABCC3, ABCC5, ABCG2). Irinotecan 60-70 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 144-150 16123050-0 2005 Gefitinib (Iressa) inhibits the CYP3A4-mediated formation of 7-ethyl-10-(4-amino-1-piperidino)carbonyloxycamptothecin but activates that of 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin from irinotecan. Irinotecan 222-232 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-38 16271446-3 2006 Irinotecan is subject to extensive metabolism by various polymorphic enzymes, including CES2 to form SN-38, members of the UGT1A subfamily, and CYP3A4 and CYP3A5, which form several pharmacologically inactive oxidation products. Irinotecan 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 144-150 15523087-0 2004 Prediction of irinotecan pharmacokinetics by use of cytochrome P450 3A4 phenotyping probes. Irinotecan 14-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-71 15727486-10 2005 The enzymes responsible for the activation, metabolism and mechanism of action of irinotecan, namely carboxylesterase 2, cytochrome P450 (CYP) 3A4, uridine diphosphate glucuronosyltransferase isoform 1A1 (UGT1A1), and topoisomerase-I, also exhibit variable interindividual activity. Irinotecan 82-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 121-146 15727486-13 2005 CYP3A4 and UGT1A1 activity levels might be predictive of irinotecan toxicity rather than efficacy. Irinotecan 57-67 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 15523087-2 2004 The response to irinotecan is variable, possibly because of interindividual variation in the expression of the enzymes that metabolize irinotecan, including cytochrome P450 3A4 (CYP3A4) and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). Irinotecan 16-26 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 157-176 15523087-2 2004 The response to irinotecan is variable, possibly because of interindividual variation in the expression of the enzymes that metabolize irinotecan, including cytochrome P450 3A4 (CYP3A4) and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). Irinotecan 16-26 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 178-184 15523087-2 2004 The response to irinotecan is variable, possibly because of interindividual variation in the expression of the enzymes that metabolize irinotecan, including cytochrome P450 3A4 (CYP3A4) and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). Irinotecan 135-145 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 157-176 15523087-2 2004 The response to irinotecan is variable, possibly because of interindividual variation in the expression of the enzymes that metabolize irinotecan, including cytochrome P450 3A4 (CYP3A4) and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). Irinotecan 135-145 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 178-184 15523087-14 2004 CONCLUSION: CYP3A4 phenotype, as assessed by midazolam clearance, is statistically significantly associated with irinotecan pharmacokinetics. Irinotecan 113-123 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 12-18 12189228-2 2002 In this study, we determined the effect of SJW on the metabolism of irinotecan, a pro-drug of SN-38 and a known substrate for CYP3A4. Irinotecan 68-78 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 126-132 12570720-6 2003 Irinotecan is subjected to be shunted between CYP3A4 mediated oxidative metabolism to form two inactive metabolites APC or NPC and tissue carboxylesterase mediated hydrolysis to form SN-38 which is eventually detoxified via glucuronidation by UGT1A1 to form SN-38G. Irinotecan 0-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 46-52 12570720-6 2003 Irinotecan is subjected to be shunted between CYP3A4 mediated oxidative metabolism to form two inactive metabolites APC or NPC and tissue carboxylesterase mediated hydrolysis to form SN-38 which is eventually detoxified via glucuronidation by UGT1A1 to form SN-38G. Irinotecan 258-263 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 46-52 12570720-7 2003 The pharmacology of this compound is further complicated by the existence of genetic inter-individual differences in activation and deactivation enzymes of irinotecan (e.g., CYP3A4, CYP3A5, UGT1A1) and sharing competitive elimination pathways with many concomitant medications, such as anticonvulsants, St. John"s Wort, and ketoconazole. Irinotecan 156-166 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 174-180 12570720-9 2003 This review highlights the latest findings in drug activation, transport mechanisms, glucuronidation, and CYP3A-mediated drug-drug interactions of irinotecan in order to unlock some of its complicated pharmacology and to provide ideas for relevant future studies into optimization of this promising agent. Irinotecan 147-157 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 106-111 15134628-5 2004 CPT-11 was administered on days 1, 8, 15, and 22 at 225 mg/m2 for patients receiving CYP3A1- or CYP3A4-inducing anticonvulsants and at 125 mg/m2 for those not on these medications. Irinotecan 0-6 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 96-102 15350151-5 2004 Drugs most prominently affected and contraindicated for concomitant use with St John"s wort are metabolised via both CYP3A4 and P-glycoprotein pathways, including HIV protease inhibitors, HIV non-nucleoside reverse transcriptase inhibitors (only CYP3A4), the immunosuppressants ciclosporin and tacrolimus, and the antineoplastic agents irinotecan and imatinib mesylate. Irinotecan 336-346 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 117-123 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). Irinotecan 177-182 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-19 11602529-0 2001 A new metabolite of irinotecan in which formation is mediated by human hepatic cytochrome P-450 3A4. Irinotecan 20-30 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 79-99 12118026-8 2002 CONCLUSION: Inhibition of CYP3A4 in cancer patients treated with irinotecan leads to significantly increased formation of SN-38. Irinotecan 65-75 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 26-32 12118026-8 2002 CONCLUSION: Inhibition of CYP3A4 in cancer patients treated with irinotecan leads to significantly increased formation of SN-38. Irinotecan 122-127 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 26-32 12019202-9 2002 In conclusion, potential clinical interactions with the metabolism of irinotecan are likely to be important for vinorelbine, which strongly inhibits irinotecan catabolism by CYP3A4 at clinically relevant concentrations, but not for the other drugs, which exert an effect at concentrations not achievable in patients. Irinotecan 70-80 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 174-180 12019202-9 2002 In conclusion, potential clinical interactions with the metabolism of irinotecan are likely to be important for vinorelbine, which strongly inhibits irinotecan catabolism by CYP3A4 at clinically relevant concentrations, but not for the other drugs, which exert an effect at concentrations not achievable in patients. Irinotecan 149-159 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 174-180 11901092-6 2002 Furthermore, CPT-11 and SN-38 were suggested to be mechanism-based inactivators of CYP3A4. Irinotecan 13-19 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 83-89 11901092-6 2002 Furthermore, CPT-11 and SN-38 were suggested to be mechanism-based inactivators of CYP3A4. Irinotecan 24-29 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 83-89 11901092-9 2002 These results mean that CPT-11 and SN-38 interact with human P450 isoforms, such as CYP2A6, CYP2C9, and CYP3A4, in vitro and imply that the significant drug interactions involving CPT-11 may be caused by a mechanism-based inactivation of CYP3A4 by SN-38 as an active metabolite of CPT-11 rather than competitive inhibition. Irinotecan 24-30 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 104-110 11901092-9 2002 These results mean that CPT-11 and SN-38 interact with human P450 isoforms, such as CYP2A6, CYP2C9, and CYP3A4, in vitro and imply that the significant drug interactions involving CPT-11 may be caused by a mechanism-based inactivation of CYP3A4 by SN-38 as an active metabolite of CPT-11 rather than competitive inhibition. Irinotecan 24-30 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 238-244 11901092-9 2002 These results mean that CPT-11 and SN-38 interact with human P450 isoforms, such as CYP2A6, CYP2C9, and CYP3A4, in vitro and imply that the significant drug interactions involving CPT-11 may be caused by a mechanism-based inactivation of CYP3A4 by SN-38 as an active metabolite of CPT-11 rather than competitive inhibition. Irinotecan 35-40 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 104-110 11901092-9 2002 These results mean that CPT-11 and SN-38 interact with human P450 isoforms, such as CYP2A6, CYP2C9, and CYP3A4, in vitro and imply that the significant drug interactions involving CPT-11 may be caused by a mechanism-based inactivation of CYP3A4 by SN-38 as an active metabolite of CPT-11 rather than competitive inhibition. Irinotecan 35-40 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 238-244 11901092-9 2002 These results mean that CPT-11 and SN-38 interact with human P450 isoforms, such as CYP2A6, CYP2C9, and CYP3A4, in vitro and imply that the significant drug interactions involving CPT-11 may be caused by a mechanism-based inactivation of CYP3A4 by SN-38 as an active metabolite of CPT-11 rather than competitive inhibition. Irinotecan 180-186 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 104-110 11901092-9 2002 These results mean that CPT-11 and SN-38 interact with human P450 isoforms, such as CYP2A6, CYP2C9, and CYP3A4, in vitro and imply that the significant drug interactions involving CPT-11 may be caused by a mechanism-based inactivation of CYP3A4 by SN-38 as an active metabolite of CPT-11 rather than competitive inhibition. Irinotecan 180-186 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 238-244 11901092-9 2002 These results mean that CPT-11 and SN-38 interact with human P450 isoforms, such as CYP2A6, CYP2C9, and CYP3A4, in vitro and imply that the significant drug interactions involving CPT-11 may be caused by a mechanism-based inactivation of CYP3A4 by SN-38 as an active metabolite of CPT-11 rather than competitive inhibition. Irinotecan 248-253 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 104-110 11901092-9 2002 These results mean that CPT-11 and SN-38 interact with human P450 isoforms, such as CYP2A6, CYP2C9, and CYP3A4, in vitro and imply that the significant drug interactions involving CPT-11 may be caused by a mechanism-based inactivation of CYP3A4 by SN-38 as an active metabolite of CPT-11 rather than competitive inhibition. Irinotecan 180-186 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 104-110 11901092-9 2002 These results mean that CPT-11 and SN-38 interact with human P450 isoforms, such as CYP2A6, CYP2C9, and CYP3A4, in vitro and imply that the significant drug interactions involving CPT-11 may be caused by a mechanism-based inactivation of CYP3A4 by SN-38 as an active metabolite of CPT-11 rather than competitive inhibition. Irinotecan 180-186 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 238-244 11602529-10 2001 These findings indicate that this newly detected metabolite is a CYP3A4-generated product that may be produced in hepatic microsomes of patients treated with CPT-11. Irinotecan 158-164 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 65-71 11901092-3 2002 CPT-11 and SN-38 competitively inhibited CYP3A4 (testosterone 6 beta-hydroxylation) activity with K(i) values of 129 and 121 microM, respectively. Irinotecan 0-6 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-47 11901092-3 2002 CPT-11 and SN-38 competitively inhibited CYP3A4 (testosterone 6 beta-hydroxylation) activity with K(i) values of 129 and 121 microM, respectively. Irinotecan 11-16 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-47 11990699-2 2002 Recent studies have shown that irinotecan also undergoes oxidative metabolism by the P450 isozyme CYP3A4, leading to the formation of a minor inactive metabolite, 7-ethyl-10-[4-N-[(5-aminopentanoic acid)-1-piperidino]-carbonyloxy-camptothecin (APC). Irinotecan 31-41 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 98-104 11990699-3 2002 The elucidation of this metabolic pathway suggests the potential for drug interactions when irinotecan is administered with other inducers or substrates of CYP3A4. Irinotecan 92-102 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 156-162 11602529-3 2001 Several oxidative metabolites of CPT-11 have been identified in humans, including 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin (APC) and 7-ethyl-10-(4-amino-1-piperidino)carbonyloxycamptothecin (NPC), generated by cytochrome P-450 3A4 (CYP3A4). Irinotecan 33-39 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 246-266 11602529-3 2001 Several oxidative metabolites of CPT-11 have been identified in humans, including 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin (APC) and 7-ethyl-10-(4-amino-1-piperidino)carbonyloxycamptothecin (NPC), generated by cytochrome P-450 3A4 (CYP3A4). Irinotecan 33-39 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 268-274 34654938-7 2022 The CYP3A4 POR UGT1A1*6 KI-Caco-2 cells were sensitive to SN-38-induced intestinal toxicity. Irinotecan 58-63 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-10 10815927-0 2000 Metabolism of irinotecan (CPT-11) by CYP3A4 and CYP3A5 in humans. Irinotecan 14-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 37-43 10815927-0 2000 Metabolism of irinotecan (CPT-11) by CYP3A4 and CYP3A5 in humans. Irinotecan 26-32 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 37-43 10815927-7 2000 Only CYP3A4 produced both APC and NPC, resulting from the oxidation of the piperidinylpiperidine side chain of CPT-11 along with metabolite M2. Irinotecan 111-117 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 5-11 10815927-11 2000 The parameters of CPT-11 biotransformation into M2 and M4 were examined using cell lines expressing, respectively, with CYP3A4 and CYP3A5, indicating that CPT-11 is preferentially metabolized by CYP3A4. Irinotecan 18-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 120-126 10815927-11 2000 The parameters of CPT-11 biotransformation into M2 and M4 were examined using cell lines expressing, respectively, with CYP3A4 and CYP3A5, indicating that CPT-11 is preferentially metabolized by CYP3A4. Irinotecan 18-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 195-201 10815927-11 2000 The parameters of CPT-11 biotransformation into M2 and M4 were examined using cell lines expressing, respectively, with CYP3A4 and CYP3A5, indicating that CPT-11 is preferentially metabolized by CYP3A4. Irinotecan 155-161 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 195-201 10815927-12 2000 In conclusion, CYP3A plays a major role in the metabolism of CPT-11, with some differences of the metabolic profile exhibited by 3A4 and 3A5. Irinotecan 61-67 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 15-20 35396702-9 2022 The findings of this study suggest that irinotecan-induced hepatotoxicity is not directly associated with genetic variables but is mostly related to concomitant use of CYP3A inducers and platinum, as well as the presence of liver metastasis and CVD. Irinotecan 40-50 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 168-173