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

Summary The pharmacokinetics of N-desmethyl-diazepam 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 (t_1/2) was significantly longer in the non-smoking volunteers than in the smokers: 54.7±17.7 versus 29.8±9.9 h (p<0.05). Peak plasma concentrations (C_max) were higher in non-smokers than in smokers, 413±106 µg/l and 245±50 µg/l, respectively (p<0.05). The sedative effect of clorazepate was less severe in smokers than in non-smokers.