THE EFFECT OF BROMAZEPAM (LEXOTAN) ADMINISTRATION ON ANTIPYRINE PHARMACOKINETICS IN HUMANS

Six healthy volunteers were given a standard regimen of bromazepam (Lexotan) (6 mg 3 times a day) for 5 days. Compliance with the study protocol was demonstrated by measuring drug concentrations at steady state. Steady-state levels of 3-hydroxybromazepam were also determined. These were much lower than the concentrations of bromazepam. Since the metabolite is less active than the parent drug, it is likely that the metabolite will contribute little to the pharmacological effects of the drug in humans. Antipyrine pharmacokinetics were studied immediately before bromazepam administration was started, after the dosing schedule was completed and 1 wk after dosing was discontinued. There were no significant changes in the disposition of antipyrine on any occasion. Although previous studies demonstrated enzyme induction in laboratory animals given high doses of bromazepam, similar effects are unlikely to occur in humans being treated with therapeutic doses of the compound.