Cytochrome P-450 3A4 and 2C8 are involved in zopiclone metabolism.
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Becquemont L, Mouajjah S, Escaffre O, Beaune P, Funck-Brentano C, Jaillon P
Cytochrome P-450 3A4 and 2C8 are involved in zopiclone metabolism.
Drug Metab Dispos. 1999 Sep;27(9):1068-73.
- PubMed ID
- 10460808 [ View in PubMed]
- Abstract
Zopiclone is a widely prescribed, nonbenzodiazepine hypnotic that is extensively metabolized by the liver in humans. The aim of the present study was to identify the human cytochrome P-450 (CYP) isoforms involved in zopiclone metabolism in vitro. Zopiclone metabolism was studied with different human liver microsomes and a panel of heterologously expressed human CYPs (CYP1A2, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, and 3A4). In human liver microsomes, zopiclone was metabolized into N-desmethyl-zopiclone (ND-Z) and N-oxide-zopiclone (NO-Z) with the following K(m) and V(m) of 78 +/- 5 and 84 +/- 19 microM, 45 +/- 1 and 54 +/- 5 pmol/min/mg for ND-Z and NO-Z generation, respectively. Ketoconazole (CYP3A inhibitor) inhibited approximately 40% of the generation of both metabolites, sulfaphenazole (CYP2C inhibitor) inhibited the formation of ND-Z, whereas alpha-naphtoflavone (CYP1A), quinidine (CYP2D6), and chlorzoxazone (CYP2E1) did not affect zopiclone metabolism. The generation of ND-Z and NO-Z were highly correlated to testosterone 6beta-hydroxylation (CYP3A activity, r = 0.95 and 0.92, respectively; p =.0001), and ND-Z was highly correlated to CYP2C8 activity (paclitaxel 6alpha-hydroxylase; r = 0.76, p =.004). Recombinant CYP2C8 had the highest enzymatic activity toward zopiclone metabolism into both its metabolites, followed by CYP2C9 and 3A4. CYP3A4 is the major enzyme involved in zopiclone metabolism in vitro, and CYP2C8 contributes significantly to ND-Z formation.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Eszopiclone Cytochrome P450 2C8 Protein Humans UnknownSubstrateDetails Eszopiclone Cytochrome P450 3A4 Protein Humans UnknownSubstrateDetails Zopiclone Cytochrome P450 2C8 Protein Humans UnknownSubstrateDetails Zopiclone Cytochrome P450 3A4 Protein Humans UnknownSubstrateDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareEszopicloneWIN 55212-2 The metabolism of Eszopiclone can be decreased when combined with WIN 55212-2. EszopicloneAldesleukin The metabolism of Eszopiclone can be decreased when combined with Aldesleukin. EszopicloneOctreotide The metabolism of Eszopiclone can be decreased when combined with Octreotide. EszopicloneFluconazole The metabolism of Eszopiclone can be decreased when combined with Fluconazole. EszopicloneLovastatin The metabolism of Eszopiclone can be decreased when combined with Lovastatin.