title: Intravenous diazepam and oral ethanol interaction.
abstract: The mechanism of the interaction between ethanol and diazepam is not known. Six healthy male subjects (aged 21 to 32 yr) were randomly assigned in a balanced crossover study to each of two treatments, 28 days apart: (1) diazepam 10 mg intravenously over 20 min, preceded by 60 min with ethanol 0.7 gm/kg (diluted to 20% v/v) orally over 15 min and followed for 8 hr by ethanol 0.15 gm/kg/hr to maintain the blood alcohol concentrations between 800 to 1,000 mg/l; (2) diazepam 10 mg intravenously over 20 min. The area under the curve (AUC) for total diazepam increased in all subjects (30.1 +/- 10.7%, mean = SD, p < 0.02) after ethanol. Since AUCfree diazepam also rose in all (mean - 26.5 +/- 17.3%) and AUC of the metabolite N-desmethyldiazepam fell (mean = 50.5 +/- 11.7%, p < 0.01) there had been inhibition of hepatic intrinsic clearance of free drug. The susceptibility of individuals to inhibition of N-desmethylation by ethanol is qualitatively determined by total drug concentrations. Estimation of free diazepam concentration coupled with measurement of metabolite affords a qualitative and quantitative evaluation of the mechanism of this interaction.
mesh_terms: D000284:Administration, Oral; D000328:Adult; D003975:Diazepam / Q000008:administration & dosage / Q000378:metabolism*; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects
chemical_list: D000431:Ethanol; D003975:Diazepam