Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study.
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Obach RS, Cox LM, Tremaine LM
Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study.
Drug Metab Dispos. 2005 Feb;33(2):262-70. Epub 2004 Nov 16.
- PubMed ID
- 15547048 [ View in PubMed]
- Abstract
The oxidative and conjugative metabolism of sertraline was examined in vitro to identify the enzymes involved in the generation of N-desmethyl, deaminated, and N-carbamoyl-glucuronidated metabolites in humans. In human liver microsomes, sertraline was N-demethylated and deaminated by cytochrome P450 (P450) enzymes with overall K(m) values of 98 and 114 microM, respectively, but the intrinsic clearance for N-demethylation was approximately 20-fold greater than for deamination. Using P450 isoform-selective inhibitors and recombinant heterologously expressed enzymes, it was demonstrated that several P450 enzymes catalyzed sertraline N-demethylation, with CYP2B6 contributing the greatest extent, and lesser contributions from CYP2C19, CYP2C9, CYP3A4, and CYP2D6. For deamination, data supported a role for CYP3A4 and CYP2C19. Purified human monoamine oxidases A and B also catalyzed sertraline deamination with comparable K(m) values (230-270 microM). Monoamine oxidase B catalyzed the reaction approximately 3-fold faster than did monoamine oxidase A. Sertraline N-carbamoyl glucuronidation was measured in human liver microsomes in bicarbonate buffer and under a CO2 atmosphere (K(m) = 50 microM) and was catalyzed at the fastest rate by recombinant human UGT2B7. The observation that multiple enzymes appear to be involved in sertraline metabolism suggests that there should be no single agent that could substantially alter the pharmacokinetics of sertraline, nor should there be any single drug-metabolizing enzyme genetic polymorphism (e.g., CYP2D6, CYP2C19, CYP2C9, UGT1A1) that could profoundly impact the pharmacokinetics of sertraline.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Sertraline Amine oxidase [flavin-containing] A Protein Humans UnknownSubstrateDetails Sertraline Amine oxidase [flavin-containing] B Protein Humans UnknownSubstrateDetails Sertraline Cytochrome P450 2B6 Protein Humans UnknownSubstrateInhibitorDetails Sertraline Cytochrome P450 2C19 Protein Humans UnknownSubstrateInhibitorDetails Sertraline Cytochrome P450 2C9 Protein Humans UnknownSubstrateInhibitorDetails Sertraline Cytochrome P450 2D6 Protein Humans UnknownSubstrateInhibitorDetails Sertraline Cytochrome P450 3A4 Protein Humans UnknownSubstrateInhibitorDetails - Drug Reactions
Reaction Details - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareSertralineEfavirenz The serum concentration of Sertraline can be decreased when it is combined with Efavirenz.
