Metabolism of quetiapine by CYP3A4 and CYP3A5 in presence or absence of cytochrome B5.
Article Details
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Bakken GV, Rudberg I, Christensen H, Molden E, Refsum H, Hermann M
Metabolism of quetiapine by CYP3A4 and CYP3A5 in presence or absence of cytochrome B5.
Drug Metab Dispos. 2009 Feb;37(2):254-8. doi: 10.1124/dmd.108.023291. Epub 2008 Nov 20.
- PubMed ID
- 19022943 [ View in PubMed]
- Abstract
The antipsychotic drug quetiapine is extensively metabolized by CYP3A4, but little is known about the possible influence of the polymorphic enzyme CYP3A5. This in vitro study investigated the relative importance of CYP3A4 and CYP3A5 in the metabolism of quetiapine and compared the metabolic pattern by the two enzymes, in the presence or absence of cytochrome b(5). Intrinsic clearance (CL(int)) of quetiapine was determined by the substrate depletion approach in CYP3A4 and CYP3A5 insect cell microsomes with or without coexpressed cytochrome b(5). Formation of the metabolites quetiapine sulfoxide, N-desalkylquetiapine, O-desalkylquetiapine, and 7-hydroxyquetiapine by CYP3A4 and CYP3A5 were compared in the different microsomal preparations. CL(int) of quetiapine by CYP3A5 was less than 35% relative to CYP3A4. CL(int) was higher (3-fold) in CYP3A4 microsomes without cytochrome b(5) compared with CYP3A4 microsomes with coexpressed cytochrome b(5), whereas in CYP3A5 microsomes CL(int) was similar for both microsomal preparations. Metabolism of quetiapine by CYP3A5 revealed a different metabolic pattern compared with CYP3A4. The results indicated that O-desalkylquetiapine constituted a higher proportion of the formed metabolites by CYP3A5 compared with CYP3A4. In conclusion, the present study indicates that CYP3A5 is of minor importance for the overall metabolism of quetiapine, regardless of the presence of cytochrome b(5). However, a different metabolic pattern by CYP3A5 compared with CYP3A4 could possibly result in different pharmacological and/or toxicological effects of quetiapine in patients expressing CYP3A5.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Quetiapine Cytochrome P450 3A4 Protein Humans UnknownSubstrateDetails Quetiapine Cytochrome P450 3A5 Protein Humans UnknownSubstrateDetails - Drug Reactions
Reaction Details Details Details Details - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareQuetiapineEfavirenz The serum concentration of Quetiapine can be increased when it is combined with Efavirenz. QuetiapineBoceprevir The serum concentration of Quetiapine can be increased when it is combined with Boceprevir. QuetiapineMethimazole The serum concentration of Quetiapine can be increased when it is combined with Methimazole. QuetiapineVoriconazole The serum concentration of Quetiapine can be increased when it is combined with Voriconazole. QuetiapineDitiocarb The serum concentration of Quetiapine can be increased when it is combined with Ditiocarb.
