PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 20977456-0 2010 Participation of CYP2C8 and CYP3A4 in the N-demethylation of imatinib in human hepatic microsomes. Nitrogen 42-43 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 28-34 18836708-8 2009 CONCLUSIONS: Voriconazole inhibits the CYP3A-mediated N-demethylation of oxycodone, drastically increasing exposure to oral oxycodone. Nitrogen 2-3 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 39-44 19897389-11 2010 CONCLUSIONS: Clarithromycin strongly increases plasma concentrations of oral S-ketamine probably by inhibiting its CYP3A-mediated N-demethylation. Nitrogen 2-3 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 115-120 18647303-8 2008 Using recombinant CYP3A4, N-dealkylation was characterized by a K(m) of 13 microM and a V(max) of 3 pmol pmol(-1) CYP min(-1). Nitrogen 26-27 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 18-24 17259447-3 2007 N-Demethylation of methadone in vitro is predominantly mediated by cytochrome P450 CYP3A4 and CYP2B6 and somewhat by CYP2C19. Nitrogen 0-1 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 83-89 18256203-11 2008 In the context of the in vitro study of CYP3A4-mediated DDI using MDZ and ketoconazole, direct MDZ N-glucuronidation may partly compensate the decrease in MDZ metabolic clearance caused by the addition of the inhibitor, thus potentially leading to underestimation, at least in vitro, of the extent of DDI. Nitrogen 99-100 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-46 18311908-4 2008 In this study, the structural characteristics of nitrogen-containing compounds, which bind to the iron atom in two CYP isoforms (CYP2C9 and CYP3A4), were investigated. Nitrogen 49-57 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 140-146 18292673-10 2008 RESULTS: At clinical concentrations, methadone enantiomer N-demethylation by recombinant CYPs 2B6, 3A4, and 2C19 was S > R, S = R, and S << R. Greater stereoselective metabolism (S > R) occurred in livers expressing high levels of CYP2B6 compared with CYP3A4. Nitrogen 58-59 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 264-270 17576805-9 2007 Relative contributions of human CYP1A2, CYP2C19, and CYP3A4 to hepatic diuron N-demethylation, based on average abundances of P450 enzymes in human liver microsomes, were approximately 60, 14, and 13%, respectively. Nitrogen 78-79 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-59 17460031-3 2007 Both t-butyl hydroxylation and N-deethylation reactions were greatly inhibited (>85%) in the presence of CYP3A-selective inhibitory antibodies and chemical inhibitors, indicating that members of the CYP3A subfamily play an important role in TPA023 metabolism. Nitrogen 31-32 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 108-113 17460031-3 2007 Both t-butyl hydroxylation and N-deethylation reactions were greatly inhibited (>85%) in the presence of CYP3A-selective inhibitory antibodies and chemical inhibitors, indicating that members of the CYP3A subfamily play an important role in TPA023 metabolism. Nitrogen 31-32 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 202-207 17460031-6 2007 Preincubation of liver microsomes with mifepristone (selectivity for CYP3A4 > CYP3A5) greatly inhibited both t-butyl hydroxylation and N-deethylation (>75%); however, the residual activities were significantly higher in the pooled CYP3A5-rich liver microsomes (p < 0.0005). Nitrogen 138-139 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 69-75 17965517-4 2007 N-dealkyation was shown to be catalyzed primarily by CYP3A4. Nitrogen 0-1 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-59 17433262-0 2007 Roles of CYP3A4 and CYP2C19 in methyl hydroxylated and N-oxidized metabolite formation from voriconazole, a new anti-fungal agent, in human liver microsomes. Nitrogen 55-56 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 9-15 17259447-4 2007 This investigation evaluated stereoselectivity, models, and kinetic parameters for methadone N-demethylation by recombinant CYP2B6, CYP3A4, and CYP2C19, and the potential for interactions between enantiomers during racemate metabolism. Nitrogen 93-94 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 132-138 16899515-5 2006 CYP3A4 activity increased by 27% postdialysis (P = 0.002 compared with predialysis) and was significantly inversely related to plasma blood urea nitrogen concentration (rs= -0.50, P = 0.012), but not to several middle molecules. Nitrogen 145-153 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 16458519-5 2006 Using a CYP26A1 homology model (based on CYP3A4) template, docking experiments were performed with MOE with multiple hydrophobic interactions observed in addition to coordination between the triazole nitrogen and the haem transition metal. Nitrogen 200-208 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-47 16700545-2 2006 The CYP3A4 isoform is inhibited by antifungal imidazoles or triazoles, which form low-spin heme iron complexes via formation of a nitrogen-ferric iron coordinate bond. Nitrogen 130-138 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-10 16700545-3 2006 However, CYP3A4 also slowly oxidizes the antifungal itraconazole (ITZ) at a site that is approximately 25 A from the triazole nitrogens, suggesting that large antifungal azoles can adopt multiple orientations within the CYP3A4 active site. Nitrogen 126-135 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 9-15 16272405-3 2006 The results indicate that CYP1A2 and CYP3A4 are the main enzymes responsible for 5-sulfoxidation and N-demethylation (34-52%), whereas CYP2D6 is the basic enzyme that catalyzes mono-2- and di-2-sulfoxidation of thioridazine in human liver (49 and 64%, respectively). Nitrogen 101-102 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 37-43 16415110-6 2006 Despite these differences in metabolism, all four ITZ stereoisomers induced a type II binding spectrum with CYP3A4, characteristic of coordination of the triazole nitrogen to the heme iron (K(s) 2.2-10.6 nM). Nitrogen 163-171 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 108-114 16802848-10 2006 Clearance is hepatic via N-oxidation by the hepatic cytochrome P450 (CYP) isoenzymes, CYP2C19, CYP2C9 and CYP3A4. Nitrogen 25-26 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 106-112 15821045-1 2005 Ifosfamide nephrotoxicity is attributed to the formation of a toxic metabolite, chloroacetaldehyde, via N-dechloroethylation, a reaction that is purportedly catalyzed by CYP3A and CYP2B6. Nitrogen 104-105 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 170-175 15821045-6 2005 In human liver microsomes matched for CYP3A4 protein content, N-dechloroethylation was more than 2-fold higher in that from donors carrying CYP3A5*1 allele that express CYP3A5 relative to that from donors homozygous for the mutant CYP3A5*3. Nitrogen 62-63 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-44 15821045-8 2005 In hepatic microsomes not expressing CYP3A5 protein, ifosfamide N-dechloroethylation was inhibited 53 to 61% and 0 to 3% by monoclonal antibodies specific for CYP3A4/5 or CYP2B6, respectively. Nitrogen 64-65 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 159-165 15585365-6 2005 The results show that CYP3A4 contributes to the oxidation of KR-60436 to pyrrole-KR-60436, O-demethylpyrrole-KR-60436 and N-dehydroxyethyl-KR-60436, and CYP2C9 and CYP2D6 play roles in demethylation of KR-60436 to form the active metabolite, O-demethyl-KR-60436. Nitrogen 122-123 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 22-28 14652237-13 2003 CONCLUSIONS: Endoxifen is an active tamoxifen metabolite that is generated via CYP3A4-mediated N-demethylation and CYP2D6-mediated hydroxylation. Nitrogen 2-3 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 79-85 15966752-6 2005 It is extensively metabolised by N-dealkylation to norbuprenorphine primarily through cytochrome P450 (CYP) 3A4. Nitrogen 33-34 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 86-111 15966756-3 2005 Hepatic and intestinal microsomal N-demethylation in vitro is catalysed mainly by cytochrome P450 (CYP) 3A4; however, the role of CYP3A in LAAM disposition in humans in vivo is unknown. Nitrogen 34-35 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 130-135 15966756-17 2005 CONCLUSION: CYP3A mediates human LAAM N-demethylation and bioactivation to norLAAM and dinorLAAM in vivo. Nitrogen 2-3 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 12-17 15501692-2 2004 Methadone is mostly metabolised in the liver; the main step consists in the N-demethylation by CYP3A4 to EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine), an inactive metabolite. Nitrogen 76-77 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 95-101 15365656-9 2004 CONCLUSION: CYP2B6, CYP2C8, CYP2D6, and CYP3A4 catalyze LOP N-demethylation in human liver microsomes, and among them, CYP2C8 and CYP3A4 may play a crucial role in LOP metabolism at the therapeutic concentrations of LOP. Nitrogen 2-3 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-46 15365656-9 2004 CONCLUSION: CYP2B6, CYP2C8, CYP2D6, and CYP3A4 catalyze LOP N-demethylation in human liver microsomes, and among them, CYP2C8 and CYP3A4 may play a crucial role in LOP metabolism at the therapeutic concentrations of LOP. Nitrogen 2-3 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 130-136 15319333-0 2004 CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes. Nitrogen 61-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 8-14 14744940-2 2004 N-dealkylated products nor-VER [2,8-bis-(3,4-dimethoxyphenyl)-2-isopropyl-6-azaoctanitrile] and D617 [2-(3,4-dimethoxyphenyl)-5-methylamino-2-isopropylvaleronitrile] were the major metabolites for all CYP3A isoforms regardless of enantiomer. Nitrogen 0-1 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 201-206 15022728-6 2004 Ketoconazole, a selective inhibitor of CYP3A4, and anti-CYP3A4 monoclonal antibodies potently inhibited both N-hydrolysis and hydroxylation of KR-31543 in human liver microsomes. Nitrogen 109-110 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 39-45 15022728-6 2004 Ketoconazole, a selective inhibitor of CYP3A4, and anti-CYP3A4 monoclonal antibodies potently inhibited both N-hydrolysis and hydroxylation of KR-31543 in human liver microsomes. Nitrogen 109-110 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-62 14651673-3 2003 In this study, we determined the percentage contribution of the three CYPs (CYP2C9, CYP2E1 and CYP3A4) to TMO N-demethylation. Nitrogen 110-111 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 95-101 12180536-4 2002 Furafylline (CYP1A2) and sulfaphenazole (CYP2C9) inhibited the N-demethylation to a lesser extent while quinidine (CYP2D6) or troleandomycine (CYP3A4) had no effect. Nitrogen 63-64 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 143-149 14606931-12 2003 Tolterodine is metabolised via CYP2D6 to the active metabolite 5-hydroxymethyl-tolterodine and via CYP3A to N-dealkylated metabolites. Nitrogen 108-109 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 99-104 12936704-0 2003 Identification of CYP3A4 and CYP2C8 as the major cytochrome P450 s responsible for morphine N-demethylation in human liver microsomes. Nitrogen 92-93 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 18-24 12721102-17 2003 The highest intrinsic clearance (V(max)/K(m)) was found for CYP1A subfamily, CYP3A4 and CYP2B6 in the case of 5- sulphoxidation, and for CYP2C19, CYP1A subfamily and CYP2B6 in the case of N-demethylation. Nitrogen 188-189 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 77-83 12721102-21 2003 Regarding the relative expression of various CYPs in human liver, the obtained results indicate that CYP1A2 and CYP3A4 are the main isoforms responsible for 5-sulphoxidation, while CYP1A2 and CYP2C19 are the basic isoforms that catalyse N-demethylation of promazine in human liver. Nitrogen 237-238 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 112-118 12610742-8 2003 RESULTS: Of the identified components in grapefruit peel, only epoxybergamottin demonstrated a concentration-dependent inhibition of the CYP3A4-mediated N-demethylation of diltiazem. Nitrogen 153-154 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 137-143 12121907-10 2002 Metabolism of 1263W94 to its primary metabolite, an N-dealkylated analog, appeared to be mediated via the isozyme CYP3A4 in humans. Nitrogen 52-53 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 114-120 12065445-0 2002 Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes. Nitrogen 55-56 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-22 12065445-8 2002 Orphenadrine, a specific inhibitor to CYP2B6, and ketoconazole, a specific inhibitor to CYP3A4, inhibited the N-demethylation of ketamine in human liver microsomes. Nitrogen 110-111 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 88-94 11408558-2 2001 Metabolism of indinavir by CYP3A4 expressing Caco-2 cells grown on filters resulted in the formation of N-dealkylation products (M5 and M6) and hydroxylation of indinavir, which were preferentially secreted into the apical compartment. Nitrogen 104-105 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 27-33 12007677-6 2002 Apparently, the probable induction of CYP3A4 by carbamazepine results in a nonstereoselective increase in N-demethylation of citalopram. Nitrogen 106-107 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-44 11695720-2 2001 CYP3A4 seems to be the most important CYP isoform in both bioactivation and N-dechloroethylation of the alkylating prodrug ifosfamide, but informations about possible gender-related differences are lacking. Nitrogen 76-77 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 11259570-8 2001 N-Demethylation of LAAM and nor-LAAM by expressed CYP3A4 was unusual, with hyperbolic velocity curves and Eadie-Hofstee plots and without evidence of positive cooperativity. Nitrogen 0-1 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 50-56 11353758-5 2001 Among the 12 cDNA-expressed CYP enzymes examined, CYP2B6, CYP2C9, and CYP3A4 showed high activities for the N-demethylation of both enantiomers at the substrate concentration of 1 mM. Nitrogen 15-16 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 70-76 11353758-7 2001 Also, the intrinsic clearance (CL(int): V(max)/K(m)) of CYP2B6 for the N-demethylation of both enantiomers were 7 to 13 times higher than those of CYP2C9 and CYP3A4. Nitrogen 71-72 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 158-164 11151747-13 2000 N-demethylated metabolites, formed by CYP3A4, were not observed in any of the cell lines. Nitrogen 0-1 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-44 11298070-9 2001 Overall, 75% or more of the N-demethylation of sildenafil at any concentration is probably attributable to CYP3A4. Nitrogen 28-29 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 107-113 11133003-6 2000 The present study indicates that CYP3A plays a major role in N-dealkylation of and oxidation back to bromperidol as well as haloperidol and suggests that modification of in vivo CYP3A activity by inhibition or induction may affect the pharmacokinetics and therapeutic effects of haloperidol and bromperidol. Nitrogen 61-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 33-38 11133003-6 2000 The present study indicates that CYP3A plays a major role in N-dealkylation of and oxidation back to bromperidol as well as haloperidol and suggests that modification of in vivo CYP3A activity by inhibition or induction may affect the pharmacokinetics and therapeutic effects of haloperidol and bromperidol. Nitrogen 61-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 178-183 10359460-9 1999 In conclusion, these data indicate that while both CYP isoforms readily catalyze both metabolic routes in vitro, CYP1A2 and CYP3A4 are more important in N-demethylation and N-oxidation, respectively. Nitrogen 153-154 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 124-130 10771285-6 2000 The additive contribution (75.3%) of human CYP3A and CYP2C to diazepam N-demethylation was also observed in the presence of both anti-CYP3A4/5 and anti-CYP2C8/9/19 monoclonal antibodies. Nitrogen 71-72 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 43-48 10771285-6 2000 The additive contribution (75.3%) of human CYP3A and CYP2C to diazepam N-demethylation was also observed in the presence of both anti-CYP3A4/5 and anti-CYP2C8/9/19 monoclonal antibodies. Nitrogen 71-72 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 134-140 11133003-0 2000 CYP3A is responsible for N-dealkylation of haloperidol and bromperidol and oxidation of their reduced forms by human liver microsomes. Nitrogen 25-26 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-5 11026737-4 2000 At 10 microM PER, a concentration consistent with anticipated in vivo liver concentrations, CYP3A4 and CYP2C9 contributed 50% and 35%, respectively, to PER-N-demethylation. Nitrogen 156-157 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 92-98 10692561-0 2000 Role of human liver microsomal CYP3A4 and CYP2B6 in catalyzing N-dechloroethylation of cyclophosphamide and ifosfamide. Nitrogen 63-64 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 31-37 10692561-3 2000 Analysis of a panel of fifteen human P450 cDNAs in the baculovirus expression system ("Supersomes") demonstrated that CYP3A4 exhibited the highest N-dechloroethylation activity toward both CPA and IFA, whereas CYP2B6 displayed high N-dechloroethylation activity toward IFA, but not CPA. Nitrogen 44-45 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 118-124 10692561-3 2000 Analysis of a panel of fifteen human P450 cDNAs in the baculovirus expression system ("Supersomes") demonstrated that CYP3A4 exhibited the highest N-dechloroethylation activity toward both CPA and IFA, whereas CYP2B6 displayed high N-dechloroethylation activity toward IFA, but not CPA. Nitrogen 147-148 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 118-124 10692561-5 2000 With CPA as substrate, CYP3A4 was shown to catalyze >/=95% of liver microsomal N-dechloroethylation, whereas with IFA as substrate, CYP3A4 catalyzed an average of approximately 70% of liver microsomal N-dechloroethylation (range = 40-90%), with the balance of this activity catalyzed by CYP2B6 (range = 10-70%, dependent on the CYP2B6 content of the liver). Nitrogen 82-83 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 23-29 10692561-5 2000 With CPA as substrate, CYP3A4 was shown to catalyze >/=95% of liver microsomal N-dechloroethylation, whereas with IFA as substrate, CYP3A4 catalyzed an average of approximately 70% of liver microsomal N-dechloroethylation (range = 40-90%), with the balance of this activity catalyzed by CYP2B6 (range = 10-70%, dependent on the CYP2B6 content of the liver). Nitrogen 82-83 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 135-141 10692561-5 2000 With CPA as substrate, CYP3A4 was shown to catalyze >/=95% of liver microsomal N-dechloroethylation, whereas with IFA as substrate, CYP3A4 catalyzed an average of approximately 70% of liver microsomal N-dechloroethylation (range = 40-90%), with the balance of this activity catalyzed by CYP2B6 (range = 10-70%, dependent on the CYP2B6 content of the liver). Nitrogen 204-205 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 23-29 10760842-0 1999 Enzymes in addition to CYP3A4 and 3A5 mediate N-demethylation of dextromethorphan in human liver microsomes. Nitrogen 46-47 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 23-29 10460803-6 1999 N-demethylation is primarily mediated by CYP2C9, CYP2C8, and CYP1A2; dihydrodiol formation by CYP2C9 and CYP1A2; deamination by CYP3A4; and side chain oxidation equally by CYP1A2, CYP2C8, CYP2C9, and CYP2C19. Nitrogen 0-1 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 128-134 10233205-11 1999 CONCLUSIONS: The N-demethylation of methadone in human liver microsomes is not markedly stereoselective, and is mediated mainly by CYP3A4 with the possible involvement of CYP2C9 and CYP2C19. Nitrogen 2-3 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 131-137 10219963-18 1999 These results suggest that both the N-demethylation and S-oxidation of zotepine are mediated mainly by CYP3A4, and that CYP1A2 and 2D6 play an important role in the 2- and 3-hydroxylation of zotepine, respectively. Nitrogen 36-37 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 103-109 10219965-6 1999 Of several human recombinant P450 isoforms, CYP3A4 had the activities for the N-deethylation of S- and R-NS-21. Nitrogen 78-79 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 44-50 10101149-0 1999 Role of CYP2B6 and CYP3A4 in the in vitro N-dechloroethylation of (R)- and (S)-ifosfamide in human liver microsomes. Nitrogen 42-43 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 19-25 10199594-10 1999 Human steroidogenic CYP17 also catalysed aminopyrine N-demethylation and the activity was comparable with that for CYP3A4 which is a dominant P450 in human liver. Nitrogen 53-54 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 115-121 10447581-4 1999 Enzyme kinetic analyses revealed the dominant role of human CYP3A4 in 4-hydroxylation and N-dechloroethylation of trofosfamide. Nitrogen 90-91 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 60-66 10189263-8 1998 The current study was undertaken to confirm the putative involvement of CYP3A4 in the N-dealkylation of Hf to Hfm by administering Hf with and without ketoconazole (KC), a specific CYP3A4 inhibitor, and measuring the resulting plasma concentration profiles of Hf and Hfm. Nitrogen 86-87 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 72-78 9600717-12 1998 These results show that CYP 3A4 is the primary hepatic CYP isoform mediating the N-demethylation of adinazolam and NDMAD. Nitrogen 81-82 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 24-31 9825830-11 1998 These results strongly suggest that back oxidation and N-dealkylation of reduced haloperidol in human liver microsomal preparations are mediated by CYP3A4. Nitrogen 55-56 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 148-154 9531513-8 1998 The Km for formation of N-dealkylated tolterodine by CYP3A4 was similar to that obtained in human liver microsomes and higher for CYP2C9 and -2C19. Nitrogen 24-25 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-59 9531513-9 1998 We conclude from these studies that the formation of 5-HM is catalyzed by CYP2D6 and that the formation of N-dealkylated tolterodine is predominantly catalyzed by CYP3A isoenzymes in human liver microsomes. Nitrogen 107-108 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 163-168 9604298-16 1998 In contrast with ZAL, the NADPH-dependent N-deethylation of M2 to M1 proceeded at only a very low rate with both human liver microsomes and cDNA-expressed CYP3A4. Nitrogen 26-27 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 155-161 9321513-5 1997 Rabbit polyclonal antibodies to CYP3A4 decreased initial rates of N-demethylation of the antihormones by up to 82%, whereas antibodies to CYP2C9 were not inhibitory. Nitrogen 66-67 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-38 9431831-12 1997 CONCLUSIONS: These results strongly suggest that the N-dealkylation of HAL in human liver microsomal preparations is mediated by CYP3A4. Nitrogen 2-3 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 129-135 9131945-10 1997 CONCLUSIONS: We conclude that CYPs 3A4, 2C9 and 2D6 together with an unidentified enzyme, but not CYPs 1A2 and 2C19, mediate the N-demethylation of AMI. Nitrogen 2-3 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-43 9278210-2 1997 The aim of this study was to investigate the role of CYP3A in the in vivo N-demethylation of IMI. Nitrogen 74-75 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-58 9278210-5 1997 CONCLUSIONS: We conclude that CYP3A may play an important role in the in vivo N-demethylation of IMI. Nitrogen 2-3 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-35 9223567-0 1997 Role of CYP3A4 in human hepatic diltiazem N-demethylation: inhibition of CYP3A4 activity by oxidized diltiazem metabolites. Nitrogen 42-43 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 8-14 9152603-7 1997 Based on the results of this study, it is concluded that the 14-(R)-hydroxylation and N-demethylation of CLAR is primarily mediated by one or more members of the human liver CYP3A subfamily. Nitrogen 86-87 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 174-179 9113345-5 1997 N-demethylation activity has recently been proposed to reflect CYP3A3/4 activity. Nitrogen 0-1 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 63-69 9084457-1 1997 OBJECTIVE: To further substantiate the role of CYP1A2 and CYP3A4 for the N-demethylation in vivo. Nitrogen 73-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 58-64 9223567-11 1997 DTZ and its N-desmethyl and N,N-didesmethyl metabolites selectively inhibited CYP3A4 activity, whereas O-desmethyl DTZ was not inhibitory. Nitrogen 28-31 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-84 9223567-16 1997 These findings suggest that N-demethylated metabolites of DTZ may contribute to CYP3A4 inhibition in vivo, especially under conditions in which N-desmethyl DTZ accumulates, such as during prolonged DTZ therapy. Nitrogen 28-29 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 80-86 9084457-2 1997 At least three different P450s appear to be responsible for the N-demethylation of imipramine to desipramine in vivo: CYP1A2, CYP2C19, and CYP3A4. Nitrogen 64-65 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 139-145 9023308-6 1997 The percentage contributions of CYP3A4 and CYP2C19 to the overall N-demethylation of CIT in human liver microsomes were estimated using a relative activity factor; respective values of 70% and 7% were calculated for microsomes obtained from livers from putative extensive metabolizers for (S)-mephenytoin 4"-hydroxylation. Nitrogen 66-67 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-38 9029042-8 1997 1 microM of the CYP3A inhibitor ketoconazole inhibited 37 +/- 19% of the N-demethylation and 86 +/- 5% of 3-hydroxylation. Nitrogen 73-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-21 9143866-8 1997 CONCLUSION: It seems that there was a good correspondence between the capacity of drugs to inhibit the O- and N-demethylation of codeine in human liver microsomes and their apparent metabolism by CYP2D6 or CYP3A4, respectively in vivo in man, suggesting that this in vitro inhibition test may be a useful screen for drugs which interact with these two important drug-metabolising enzymes. Nitrogen 2-3 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 206-212 9110356-3 1997 cDNA expressed human cytochrome P-450 3A4, 2C19 and 2D6 isozymes, but not CYP1A2, were identified to be involved in N-demethylation of CIT enantiomers. Nitrogen 2-3 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 21-41 8894516-5 1996 Ciprofloxacin and norfloxacin significantly depressed the N-demethylation of erythromycin by CYP3A4 in human microsomes and by CYP3A2 in rat microsomes. Nitrogen 58-59 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 93-99 9143866-1 1997 OBJECTIVE: The O- and N-demethylation of codeine is catalysed by CYP2D6 and CYP3A4 respectively. Nitrogen 22-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 76-82 8742227-2 1996 N-Hydroxylation of dapsone in human liver microsomes has been shown to be mediated largely by CYP3A4. Nitrogen 0-1 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 94-100 8861661-6 1996 In addition, in healthy volunteers and cancer patients, the N-demethylation of DM correlated with the CYP3A-mediated metabolism of verapamil and tamoxifen. Nitrogen 60-61 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 102-107 8953507-12 1996 Of seven cDNA-expressed P450 isoforms in man (CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1 and CYP3A4), CYP3A4, CYP2D6 and CYP1A2 isozyme exhibited substantial catalytic activity of N-demethylation of YM17E. Nitrogen 11-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 97-103 8667235-5 1996 Thus, the results are consistent with the assumption that the N-demethylation of clomipramine is catalyzed by CYP3A4. Nitrogen 62-63 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 110-116 8640913-2 1996 Previously, we have shown that low CYP3A activity, measured by dapsone N-hydroxylation, and high CYP2D6 activity, assessed by debrisoquine 4-hydroxylation, were significant susceptibility risk factors in developing aggressive bladder cancer. Nitrogen 71-72 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 35-40 8712396-5 1996 Rates of N-dealkylated metabolite formation significantly correlated with nifedipine oxidation activity (a marker of CYP3A4 activity) for fentanyl and sufentanil (r = 0.93 and 0.87, n = 18, respectively), but not with the oxidation activity for ethoxyresorufin (CYP1A2), S-mephenytoin (CYP2C19), bufuralol (CYP2D6), or chlorzoxazone (CYP2E1). Nitrogen 9-10 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 117-123 7473143-0 1995 N-demethylation of amitriptyline in vitro: role of cytochrome P-450 3A (CYP3A) isoforms and effect of metabolic inhibitors. Nitrogen 0-1 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 51-70 8712396-6 1996 Gestodene and troleandomycin (chemical inhibitors of CYP3A4) and antibody to CYP3A4 inhibited N-dealkylation of fentanyl and sufentanil. Nitrogen 94-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 77-83 8712396-8 1996 Recombinant CYP3A4 expressed in Escherichia coli showed N-dealkylation activity of fentanyl and sufentanil, while expressed CYP1A2, 2C10, and 2E1 enzymes did not. Nitrogen 56-57 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 12-18 7473143-0 1995 N-demethylation of amitriptyline in vitro: role of cytochrome P-450 3A (CYP3A) isoforms and effect of metabolic inhibitors. Nitrogen 0-1 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 72-77 1630156-4 1992 In human liver microsomes, the glucocorticoid-inducible cytochrome P-450IIIA, CYP3A, catalyzes the N-demethylation of erythromycin. Nitrogen 99-100 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-83 7756104-6 1995 The immunoidentified CYP2D6 and CYP3A4 correlated with the rates of O-deethylation (r = 0.972) and N-demethylation (r = 0.969), respectively. Nitrogen 99-100 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-38 8204106-9 1994 Prior incubation of microsomes with 100 microM gestodene, known to be a selective mechanism-based inhibitor of CYP3A4 in the presence of NADPH, led to 76 +/- 6 and 76 +/- 5% (N = 5 samples) reductions in the N-demethylation and formation of TOR III, respectively. Nitrogen 137-138 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 111-117 8304968-7 1994 These results indicated that the N-demethylation of TMO is catalysed mainly by CYP2C11 and 2B1 in rat hepatic microsomes, and that human CYP3A4 and an unspecified isoform of the 2C subfamilies contribute to TMO N-demethylation in human liver. Nitrogen 211-212 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 137-143 7905403-0 1993 Evidence for CYP3A-mediated N-deethylation of amiodarone in human liver microsomal fractions. Nitrogen 28-29 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 13-18 8220439-4 1993 In microsomes, the N-demethylation was inhibited by antibodies raised against CYP3A subfamily members although fetal microsomes were much less sensitive to immunoinhibition than adult microsomes. Nitrogen 19-20 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-83 8220439-10 1993 These data clearly suggest that the N-demethylation of dextromethorphan is dependent on CYP3A and that both CYP2D6 and CYP3A are involved in the overall metabolism of dextromethorphan. Nitrogen 36-37 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 88-93 8423765-13 1993 Both CYP1A2 and CYP3A4 catalyzed N-dealkylation of propafenone, with specific activities of 0.32 pmol/min/pmol of P450 and 0.16 pmol/min/pmol of P450, respectively. Nitrogen 33-34 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-22 7654131-7 1995 CYP3A enzymes are principally responsible for the cocaine N-demethylation in human and mouse liver microsomes. Nitrogen 58-59 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-5 8161344-7 1994 A strong correlation (P < 0.001) was observed between CYP3A4 expression and both activation and N-dechloroethylation of ifosfamide. Nitrogen 99-100 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 57-63 1306804-6 1992 The N-demethylation pathway to 3-methoxymorphinan is accessory and is dependent on the CYP3A subfamily. Nitrogen 4-5 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 87-92 30902024-14 2020 These findings demonstrate that the relative CYP3A4, CYP2B6, and CYP2C19 involvement in meperidine N-demethylation depends on the enzyme activities in individual human liver microsomal samples. Nitrogen 99-100 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 45-51 31286572-5 2020 An electrochemical enzymatic system based on CYP3A4 immobilized on a screen-printed electrode was used to show that abiraterone acts as a competitive inhibitor toward erythromycin N-demethylase activity of CYP3A4 (apparent Ki = 8.1 +- 1.2 muM), while erythromycin and its products of enzymatic metabolism do not affect abiraterone N-oxidation by CYP3A4. Nitrogen 180-181 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 45-51 31286572-5 2020 An electrochemical enzymatic system based on CYP3A4 immobilized on a screen-printed electrode was used to show that abiraterone acts as a competitive inhibitor toward erythromycin N-demethylase activity of CYP3A4 (apparent Ki = 8.1 +- 1.2 muM), while erythromycin and its products of enzymatic metabolism do not affect abiraterone N-oxidation by CYP3A4. Nitrogen 180-181 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 206-212 31286572-5 2020 An electrochemical enzymatic system based on CYP3A4 immobilized on a screen-printed electrode was used to show that abiraterone acts as a competitive inhibitor toward erythromycin N-demethylase activity of CYP3A4 (apparent Ki = 8.1 +- 1.2 muM), while erythromycin and its products of enzymatic metabolism do not affect abiraterone N-oxidation by CYP3A4. Nitrogen 180-181 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 206-212 30902024-8 2020 The catalytic efficiency (kcat/Km) for meperidine N-demethylation was similar between recombinant CYP2B6 and CYP2C19, but markedly lower by CYP3A4. Nitrogen 50-51 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 140-146 33674271-4 2021 The N-oxidation of PQ to PN1 was mainly mediated by CYP3A4, and PN1 can rapidly reduce back to PQ via CYP/FMO enzymes. Nitrogen 4-5 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-58 33674271-5 2021 In accordance with these findings, the CYP non-selective inhibitor (1-ABT) or CYP3A4 inhibitor (ketoconazole) inhibited the N-oxidation pathway in liver microsomes (>90%), and the reduction metabolism was inhibited by 1-ABT (>90%) or methimazole (~50%). Nitrogen 124-125 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-84 33048135-12 2021 CYP3A4 was involved in the formation of all phase I metabolites of both NPS, while UGT1A4 and UGT2B10 catalyzed their N-glucuronidation. Nitrogen 72-73 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 31929398-15 2020 The AUC ratios of norbuprenorphine and norbuprenorphine glucuronide to buprenorphine, a measure of CYP3A mediated N-demethylation, were 1.89, 1.84, and 1.33 during the 1 and 2, 3 trimesters, and postpartum, respectively. Nitrogen 114-115 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 99-104 31605674-6 2019 The findings confirmed that CYP3A4 was a major contributor (at least 30% total metabolism) to all three of the possible N-dealkylation pathways; however, CYP2C9, and not CYP2C19, played a critical role in terbinafine metabolism and even exceeded CYP3A4 contributions for terbinafine N-demethylation. Nitrogen 120-121 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 28-34 31605674-6 2019 The findings confirmed that CYP3A4 was a major contributor (at least 30% total metabolism) to all three of the possible N-dealkylation pathways; however, CYP2C9, and not CYP2C19, played a critical role in terbinafine metabolism and even exceeded CYP3A4 contributions for terbinafine N-demethylation. Nitrogen 283-284 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 28-34 30087611-6 2018 Inhibition studies using human liver microsomes showed that CYP3A4, 2B6, and 2C9 together contributed 19.0 +- 2.6% (mean +- 95%CI) to O-demethylation, 4.0 +- 0.7% to alpha-hydroxylation, and 7.6 +- 1.7% to N-dealkylation of metoprolol. Nitrogen 206-207 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 60-71 31312984-4 2019 In this study, the N- and alpha-carbon oxidation processes of lapatinib catalyzed by CYP3A4 were explored by density functional theory method. Nitrogen 19-20 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 85-91 31028057-2 2019 A previous study involving human hepatocytes showed the primary route of midazolam metabolism, 1"-hydroxylation, shifted to N-glucuronidation in the presence of the CYP3A inhibitor ketoconazole, which may lead to an overprediction of the magnitude of a xenobiotic-midazolam interaction. Nitrogen 124-125 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 165-170 30912932-5 2019 Comparison of the subseries and individual compounds showed that CYP3A4 only weakly discriminates between side-group configurations, associates more tightly with the pyridyl-ethyl-linker analogues, and strongly disfavors the N-containing backbone. Nitrogen 225-226 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 65-71 30205091-2 2018 Methadone undergoes N-demethylation by multiple cytochrome P450 (CYP) enzymes including CYP3A4, CYP2B6, CYP2C19, CYP2D6, CYP2C9, and CYP2C8. Nitrogen 20-21 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 88-94 29129847-2 2018 N-dechloroethylation of CP mediated by the enzyme CYP3A4 yields nephrotoxic and neurotoxic chloroacetaldehyde (CAA) in equimolar amount to DECP. Nitrogen 0-1 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 50-56 25737032-4 2016 Pazopanib can be well docked into the activity cavity of CYP3A4, and the interaction structure in pazopanib was methyl group located besides nitrogen in the five-membered ring. Nitrogen 141-149 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 57-63 27457784-9 2016 Further, incubations of M11 with recombinant P450s showed that M12 is formed via N-dealkylation of M11 by CYP3A4, CYP2C19, and CYP1A2. Nitrogen 81-82 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 106-112 29061956-2 2017 Most oxycodone is metabolized by N-demethylation to noroxycodone by CYP3A. Nitrogen 33-34 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 68-73 27692933-2 2017 The N-demethylation by CYP3A4/5 and the O-demethylation by CYP2D6 in human liver microsomes (HLM) followed Michaelis-Menten kinetics, with intrinsic clearances of 1.46muL/min/mg and 0.35muL/min/mg, respectively. Nitrogen 4-5 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 23-29 26741368-4 2016 Methamphetamine-CYP3A4 docking showed that methamphetamine binds to the heme of CYP3A4 in two modes, both leading to N-demethylation. Nitrogen 117-118 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-22 26741368-4 2016 Methamphetamine-CYP3A4 docking showed that methamphetamine binds to the heme of CYP3A4 in two modes, both leading to N-demethylation. Nitrogen 117-118 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 80-86 26276083-6 2015 Studies showed the involvement of CYP1A2, CYP2B6, CYP2C19, and CYP3A4 in N-dealkylation of all three compounds and additionally CYP2D6 for lefetamine and NEDPA. Nitrogen 73-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 63-69 26104860-3 2015 Enantioselective CE with highly sulfated gamma-cyclodextrin as chiral selector was employed for analyzing in vitro (i) the kinetics of the N-demethylation of ketamine mediated by canine CYP3A12 and (ii) interactions occurring with racemic medetomidine and dexmedetomidine during coincubation with ketamine and canine liver microsomes (CLM), canine CYP3A12, human liver microsomes (HLM), and human CYP3A4. Nitrogen 139-140 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 397-403 25121773-2 2014 The predominant metabolic pathway of oxycodone is CYP3A4-mediated N-demethylation to noroxycodone, while a minor proportion undergoes 3-O-demethylation to oxymorphone by CYP2D6. Nitrogen 66-67 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 50-56 26456786-9 2015 Using human CYPs, CYP1A2, CYP2C19, CYP2D6, and/or CYP3A4 were found to catalyze N-oxide formation and N-, O-demethylation and/or oxidation. Nitrogen 80-81 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 50-56 25382218-7 2015 The new approach was thoroughly validated for the CYP3A4-mediated N-demethylation pathway of ketamine and applied to the determination of its kinetic parameters and the inhibition characteristics in presence of ketoconazole and dexmedetomidine. Nitrogen 66-67 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 50-56 25651456-1 2015 In humans, the metabolic bioactivation of pyrrolizidine alkaloids (PAs) is mediated mainly by cytochrome P450 3A4 (CYP3A4) via the hydroxylation of their necine bases at C3 or C8 of heliotridine- and retronecine-type PAs or at the N atom of the methyl substituent of otonecine-type PAs. Nitrogen 231-232 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 94-113 25651456-1 2015 In humans, the metabolic bioactivation of pyrrolizidine alkaloids (PAs) is mediated mainly by cytochrome P450 3A4 (CYP3A4) via the hydroxylation of their necine bases at C3 or C8 of heliotridine- and retronecine-type PAs or at the N atom of the methyl substituent of otonecine-type PAs. Nitrogen 231-232 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 115-121 25327846-0 2015 Introduction of a nitrogen-containing side chain appended on C-10 of cethromycin leads to reduced CYP3A4 inhibition (WO2014049356A1). Nitrogen 18-26 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 98-104 24860154-2 2014 It is metabolized primarily by the cytochrome P450 isoenzyme 3A4 (CYP3A4) to a less-active N-monodesmethyl metabolite. Nitrogen 91-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 35-64 24860154-2 2014 It is metabolized primarily by the cytochrome P450 isoenzyme 3A4 (CYP3A4) to a less-active N-monodesmethyl metabolite. Nitrogen 91-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 66-72 24841887-7 2014 The obtained results indicate that the catalysis of levomepromazine 5-sulfoxidation and N-demethylation in humans shows a strict CYP3A4 preference, especially at a therapeutic drug concentration. Nitrogen 88-89 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 129-135 23988488-9 2013 Using the relative activity factor approach, the hepatic clearance was calculated to be 27 and 73% for 2-O-demethylation by CYP1A2 and CYP3A4, 82, 3, and 15% for 9-O-demethylation by CYP1A2, CYP2C19, and CYP2D6, and finally <1 and 99% for N-demethylation by CYP2D6 and CYP3A4. Nitrogen 242-243 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 135-141 25505590-5 2014 CYP3A isoforms mostly contributed to N-debutylation while hydroxylation on the butyl-benzofuran moiety was catalyzed by CYP2D6. Nitrogen 37-38 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-5 23550066-1 2013 Ketamine is primarily metabolized to norketamine by hepatic CYP2B6 and CYP3A4-mediated N-demethylation. Nitrogen 87-88 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 71-77 23774830-6 2013 The enzyme kinetic studies showed that the initial metabolic step in humans, the N-deethylation, was catalyzed by CYP2B6 and CYP3A4. Nitrogen 81-82 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 125-131 23666577-4 2013 O-demethylation is catalyzed by the highly polymorphic CYP2D6 and N-demethylation by several enzymes, CYP2C19, CYP2C9, and CYP3A4. Nitrogen 66-67 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 123-129 21983822-1 2011 Enantioselective CE with sulfated cyclodextrins as chiral selectors was used to determine the CYP3A4-catalyzed N-demethylation kinetics of ketamine to norketamine and its inhibition in the presence of ketoconazole in vitro. Nitrogen 111-112 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 94-100 23404373-6 2013 The abundance of one metabolite, the N-dealkylated nitroso/oxime lapatinib metabolite (M9), correlated directly with the prevalence or the disruption of the MI complex with CYP3A4. Nitrogen 37-38 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 173-179 23404373-9 2013 Our findings support the mechanism of lapatinib CYP3A4 inactivation as MI complex formation with the nitroso metabolite formed through the secondary hydroxylamine and nitrone pathway, rather than by N-dealkylation to the primary amine followed by N-hydroxylation and dehydrogenation as is usually assumed. Nitrogen 199-200 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 48-54 22187487-10 2012 The molecular docking study showed that the N-ethyl moiety of CP-945,598 can access to the heme iron-oxo of CYP3A4 in an energetically favored orientation. Nitrogen 44-45 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 108-114 23361230-10 2013 They were also involved in the N-demethylation of the analogue methamphetamine and CYP2C19, CYP2D6, and CYP3A4 in its ring hydroxylation. Nitrogen 31-32 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 104-110 22949220-0 2012 Electrophoretically mediated microanalysis for characterization of the enantioselective CYP3A4 catalyzed N-demethylation of ketamine. Nitrogen 105-106 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 88-94 22949220-2 2012 An EMMA method was developed to investigate the stereoselectivity of the CYP3A4-mediated N-demethylation of ketamine. Nitrogen 89-90 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 73-79 22106171-1 2012 Itraconazole (ITZ) is a mixture of four cis-stereoisomers that inhibit CYP3A4 potently and coordinate CYP3A4 heme via the triazole nitrogen. Nitrogen 131-139 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 71-77 22106171-1 2012 Itraconazole (ITZ) is a mixture of four cis-stereoisomers that inhibit CYP3A4 potently and coordinate CYP3A4 heme via the triazole nitrogen. Nitrogen 131-139 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 102-108 22023129-7 2011 For all 3 species, inhibitors of CYP3A4, CYP2A6, CYP2C19, CYP2B6, and CYP2C9 diminished N-demethylation of ketamine. Nitrogen 88-89 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 33-39 20849451-4 2011 The P450 CYP3A4 enzyme is responsible for the major metabolic N-dealkylation pathway. Nitrogen 62-63 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 9-15