Metabolic interaction between ethanol, high-dose alprazolam and its two main metabolites using human liver microsomes in vitro.
Alprazolam is widely used as a short-acting antidepressant and anxiolytic agent and its effect appears at very low doses while ethanol is used as a social drug worldwide. Sometimes, toxic interactions occur following combined administration of these two drugs. In this study we have investigated the interaction between ethanol and high-dose alprazolam using human liver microsomes in vitro. The interaction effects between ethanol and alprazolam were examined by a mixed-function oxidation reaction using a human liver microsomal preparation. Alprazolam and its two main metabolites (alpha-hydroxyalprazolam: alpha-OH alprazolam, 4-hydroxyalprazolam: 4-OH alprazolam) were measured by HPLC/UV. The production of 4-OH alprazolam, one main metabolite of alprazolam, was weakly inhibited by higher dose of ethanol, but not alpha-OH alprazolam. These results using a human liver microsomal preparation show that the production of 4-OH alprazolam is weakly inhibited by ethanol but not alpha-OH alprazolam. Toxic levels may be reached by simultaneous administration of ethanol and high-dose alprazolam.
Tanaka
Einosuke
E
Department of Legal Medicine, Institute of Community Medicine, University of Tsukuba, Ibaraki-ken, Japan. einosuke@md.tsukuba.ac.jp
Nakamura
Takako
T
Terada
Masaru
M
Shinozuka
Tatsuo
T
Honda
Katsuya
K
D000525:Alprazolam / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D014151:Anti-Anxiety Agents / Q000378:metabolism* / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000378:metabolism* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000378:metabolism* / Q000494:pharmacology; D053593:Forensic Toxicology; D006801:Humans; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism
D014151:Anti-Anxiety Agents; D002492:Central Nervous System Depressants; C032318:alpha-hydroxyalprazolam; D000431:Ethanol; C503150:4-hydroxyalprazolam; D000525:Alprazolam