Comparative pharmacokinetics of alprazolam and lorazepam in humans and in African Green Monkeys

Abstract

The comparative pharmacokinetics of alprazolam and lorazepam were evaluated in African Green Monkeys and in healthy male human volunteers. Six monkeys received a single 250 micrograms/kg oral dose of alprazolam and of lorazepam on two separate occasions. Mean kinetic values for the two drugs, respectively, were: elimination half-life, 5.7 and 1.7 h; oral clearance, 5.5 and 40.2 ml/min/kg. Healthy male volunteers (n = 22) received a single 1 mg oral dose of alprazolam; another group (n = 24) received a single 2 mg oral dose of lorazepam. Mean values of elimination half-life in humans (11.5 and 12.4 h, for alprazolam and lorazepam, respectively) were substantially longer than corresponding values in the primate animal model, and human values of clearance (0.85 and 1.40 ml/min/kg) likewise were much lower. However, in humans, kinetic differences between the two drugs were much smaller than in the primate animals. Thus comparative studies of the behavioral effects of these two drugs in African Green Monkeys should utilize relative dosages that reflect the pharmacokinetic properties of the drugs in that species. Use of dosage ratios analogous to those used in humans may lead to results that cannot be extrapolated to humans.