Pharmacokinetics of N-desmethyldiazepam after a single oral dose of clorazepate: the effect of smoking

Abstract

The pharmacokinetics of N-desmethyldiazepam was evaluated after oral administration of clorazepate 20 mg to 12 healthy male volunteers (6 smokers; 6 non-smokers), aged 23-29 years. Plasma levels of desmethyldiazepam were measured by gas liquid chromatography. The half life of elimination (t1/2 beta) was significantly longer in the non-smoking volunteers than in the smokers: 54.7 +17.7 versus 29.8 +9.9 h (p less than 0.05). Peak plasma concentrations (Cmax) were higher in non-smokers than in smokers, 413 +106 micrograms/l and 245 +50 micrograms/l, respectively (p less than 0.05). The sedative effect of clorazepate was less severe in smokers than in non-smokers.