Identification of enzymes responsible for primary and sequential oxygenation reactions of capravirine in human liver microsomes.
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Bu HZ, Zhao P, Kang P, Pool WF, Wu EY
Identification of enzymes responsible for primary and sequential oxygenation reactions of capravirine in human liver microsomes.
Drug Metab Dispos. 2006 Nov;34(11):1798-802. Epub 2006 Aug 16.
- PubMed ID
- 16914510 [ View in PubMed]
- Abstract
Capravirine, a new non-nucleoside reverse transcriptase inhibitor, undergoes extensive oxygenation reactions, including N-oxidation, sulfoxidation, sulfonation, and hydroxylation in humans. Numerous primary (mono-oxygenated) and sequential (di-, tri-, and tetraoxygenated) metabolites of capravirine are formed via the individual or combined oxygenation pathways. In this study, cytochrome P450 enzymes responsible for the primary and sequential oxygenation reactions of capravirine in human liver microsomes were identified at the specific pathway level. The total oxygenation of capravirine is mediated predominantly (>90%) by CYP3A4 and marginally (<10%) by CYP2C8, 2C9, and 2C19 in humans. Specifically, each of the two major mono-oxygenated metabolites C23 (sulfoxide) and C26 (N-oxide), is mediated predominantly (>90%) by CYP3A4 and slightly (<10%) by CYP2C8, the minor tertiary hydroxylated metabolite C19 by CYP3A4, 2C8, and 2C19, and the minor primary hydroxylated metabolite C20 by CYP3A4, 2C8, and 2C9. However, all sequential oxygenation reactions are mediated exclusively by CYP3A4. Due to their relatively insignificant contributions of C19 and C20 to total capravirine metabolism, no attempt was made to determine relative contributions of cytochrome P450 enzymes to the formation of the two minor metabolites.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Capravirine Cytochrome P450 2C19 Protein Humans UnknownSubstrateDetails Capravirine Cytochrome P450 2C8 Protein Humans UnknownSubstrateDetails Capravirine Cytochrome P450 2C9 Protein Humans UnknownSubstrateDetails Capravirine Cytochrome P450 3A4 Protein Humans UnknownSubstrateDetails