DISPOSITION OF NETOBIMIN, ALBENDAZOLE, AND ITS METABOLITES IN THE PREGNANT RAT - DEVELOPMENTAL TOXICITY

Netobimin (NTB), a benzimidazole prodrug with a goad anthelmintic spec trum, was administered orally to female rats at a dose of 59.5 mg NTB/ kg, to study its pharmacokinetic behavior and the disposition of its m ost important metabolites, albendazole (ABZ), albendazole sulfoxide (A BZSO), and albendazole sulfone (ABZSO,). ABZ was found in plasma after 6 hr. Peak plasma concentrations (C-max) and areas under curves (AUG) of ABZSO were eight- and fourfold higher, respectively, than those of ABZSO(2). To study NTB disposition in pregnant rats, three different drug doses (50, 59.5, and 70.7 mg/kg) were given. No significant diffe rences were found between plasma concentrations for each metabolite at the three doses studied. Only ABZ concentrations rose slightly as clo se increased. ABZ, ABZSO, and ABZSO(2) were found in amniotic sacs and embryos at concentrations that were higher than plasma at the same ti mes. The fetuses obtained after administration of each of the doses of NTB were studied to detect developmental toxicity. A significant corr elation was found between rate of developmental toxicity and metabolit e concentration, ABZSO embryo concentrations could be the main factor accounting for toxicity. (C) 1997 Academic Press.