Identification of human cytochrome P450 enzymes involved in the formation of 4-hydroxyestazolam from estazolam.
Article Details
- CitationCopy to clipboard
Miura M, Otani K, Ohkubo T
Identification of human cytochrome P450 enzymes involved in the formation of 4-hydroxyestazolam from estazolam.
Xenobiotica. 2005 May;35(5):455-65.
- PubMed ID
- 16012077 [ View in PubMed]
- Abstract
To predict drug interactions with estazolam, the biotransformation of estazolam to its major hydoxylated metabolite, 4-hydroxyestazolam was studied in vitro using pooled human liver microsomes and individual expressed human cytochrome P450 (CYP) enzymes. Estazolam was metabolized to 4-hydroxyestazolam according to the Hill kinetic model in pooled human liver microsomes. The Km value for the 4-hydroxylation of estazolam was 24.1 microM, and the Vmax value was 52.6 pmol min(-1)mg(-1) protein. The formation of 4-hydroxyestazolam from estazolam in pooled human liver microsomes was significantly inhibited by itraconazole and erythromycin, specific CYP3A4 inhibitors, in a dose-dependent manner, with IC50 values of 1.1 and 12.8 microM, respectively. When estazolam was incubated with expressed human CYP enzymes (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4), it was metabolized only by CYP3A4. In conclusion, the biotransformation of estazolam to 4-hydroxyestazolam was catalyzed by CYP3A4.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Estazolam Cytochrome P450 3A4 Protein Humans UnknownSubstrateDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareEstazolamErythromycin The serum concentration of Estazolam can be increased when it is combined with Erythromycin. EstazolamSirolimus The serum concentration of Estazolam can be increased when it is combined with Sirolimus. EstazolamDirithromycin The serum concentration of Estazolam can be increased when it is combined with Dirithromycin. EstazolamTelithromycin The serum concentration of Estazolam can be increased when it is combined with Telithromycin. EstazolamCandicidin The serum concentration of Estazolam can be increased when it is combined with Candicidin.