CLINICAL PHARMACOKINETICS OF HIGH-DOSE MEBENDAZOLE IN PATIENTS TREATED FOR CYSTIC HYDATID-DISEASE

The plasma concentrations of mebendazole and its metabolites were monitored in 12 patients after receiving a 10 mg/kg dose for cystic hydatid disease. The mebendazole plasma concentration-time profiles differed considerably between patients. Elimination half-lives ranged from 2.8-9.0 h, time to peak plasma concentration after dosing ranged from 1.5-7.25 h and peak plasma concentrations ranged from 17.5 to 500 ng/ml. The mean peak plasma concentration of mebendazole after an initial dose (69.5 ng/ml) was lower than found in patients during chronic therapy (137.4 ng/ml). The plasma AUCT [area under the mebendazole concentration vs. time curve for 1 dosing interval] for the major metabolites of mebendazole (methyl 5-(.alpha.-hydroxybenzyl)-2-benzimidazole carbamate and 2-amino-5 benzoylbenzimidazole) were about 5 times the plasma AUCT found for mebendazole in patients on chronic therapy. The slower clearance of these polar metabolites relative to mebendazole evidently resulted from enterohepatic recycling. Since mebendazole is also highly plasma protein bound, caution should be observed in administering mebendazole to patients with liver disease. Concentrations of mebendazole found in the tissue and cyst material collected from 2 patients during surgery ranged from 59.5 to 206.6 ng/g wet wt.