A study of the in vitro interaction between ethanol, and triazolam and its two metabolites using human liver microsomes.
OBJECTIVE
Triazolam is widely used as an ultrashort-acting anxiolytic drug and hypnosedatives and its effect appears at very low doses. 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 alcohol and triazolam in vitro.


METHODS
The interaction effects between alcohol and triazolam were examined by a mixed-function oxidation reaction using a human liver microsomal preparation. Triazolam and its two metabolites (alpha-hydroxytriazolam: alpha-OH triazolam, 4-hydroxytriazolam: 4-OH triazolam) were measured by HPLC/UV.


RESULTS
The production of alpha-OH triazolam and 4-OH triazolam was shown to be weakly inhibited by 13-29% (p < 0.05) and 8-14%,respectively, by ethanol (20-80 mM).


CONCLUSIONS
These results using a human liver microsomal preparation show that the formation of both metabolites of triazolam is weakly inhibited by ethanol. Toxic levels may be reached by simultaneous administration of ethanol and triazolam.
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
D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D049429:Forensic Pathology; D006801:Humans; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism*; D014229:Triazolam / Q000031:analogs & derivatives* / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D002492:Central Nervous System Depressants; D014229:Triazolam; D000431:Ethanol