Kinetics of diazepam, midazolam, and lorazepam in cigarette smokers

Ten otherwise healthy cigarette smokers (mean, 31 cigarettes per day), and ten nonsmoking control volunteers matched for age, weight, and sex received single intravenous doses of diazepam (5 to 10 mg), midazolam (5 mg), and lorazepam (2 mg) on three separate occasions. Kinetics of each benzodiazepine were determined from multiple serum concentrations measured after each dose. In non-smoking vs smoking subjects, there was no significant difference in mean clearance of diazepam (0.44 vs 0.47 ml/min/kg), midazolam (9.6 vs 7.1 ml/min/kg), or lorazepam (0.96 vs 1.08 ml/min/kg). Thus, differences in pharmacokinetics are unlikely to account for altered sensitivity to benzodiazepines that may occur in cigarette smokers.