Comparative pharmacokinetics of acetohexamide and its metabolite, hydroxyhexamide in laboratory animals.

The pharmacokinetic profiles of the hypoglycemic agent, acetohexamide (AH) and its major active metabolite, hydroxyhexamide (HH) were studied in three species of laboratory animals after intraperitoneal (ipl) administration in comparison with those after intravenous (iv) administration of AH and of the preformed metabolite HH. Reductive biotransformation of AH to HH was reversible in rats and guinea pigs, while it was irreversible in rabbits. The parameters of reversible drug-metabolite pharmacokinetics were calculated, including essential clearances of reversible and irreversible elimination, volumes of distribution at the steady state and sojourn times or turnover rates of the metabolite pair. An interconversion model, which incorporated a first-pass metabolism, was applied to the disposition kinetics of AH and HH, and the available fractions of AH and generated metabolite HH in each species were elucidated.