The metabolic and pharmacokinetic disposition of mebendazole in the rat

Summary

The metabolism and pharmacokinetics of mebendazole was studied in rats using [2^′-³H]-mebendazole (biologically stable; specific activity 383.9 (mCi/mMol) and [2-^l4C]-mebendazole (specific activity 2.57 mCi/mMol). Analyses were performed by high pressure liquid chromatography and liquid scintillation spectrometry. About 85% of an intravenous dose was eliminated with the bile and the remainder with the urine. The majority of the dose was recovered as conjugated metabolites. The major metabolite (methyl-5(6)-(α-hyciroxybenzyl)-2-benzimidazole carbamate) accounted for about 77 % of the total recovered and 99 % of it was conjugated. Anaerobic metabolism studies conductedin vitro with intestinal micro-organisms obtained from rats indicated that metabolism of mebendazole did not occur in the gut, but that the intestinal microflora was able to hydrolyse conjugated metabolites which were eliminated with the bile. Mebendazole was found to have a biphasic elimination profile after intravenous administration. Its terminal plasma elimination half-life was 3.2 hours and its re-distribution half-life was 0.4 hour. After oral administration, as a solution in aqueous dimethyl sulphoxide, a bioavailability of 53 % was obtained.