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Souhaili-el Amri H, Fargetton X, Benoit E, Totis M, Batt AM: Inducing effect of albendazole on rat liver drug-metabolizing enzymes and metabolite pharmacokinetics. Toxicol Appl Pharmacol. 1988 Jan;92(1):141-9.
Albendazole (ABZ), methyl (5-(propylthio)-1H-benzimidazol-2-yl) carbamate, is a broad spectrum anthelmintic drug. S-oxidation to the sulfoxide (SO-ABZ) and the sulfone (SO2-ABZ) are the first steps of its bioconversion. SO-ABZ is pharmacologically active and embryotoxic in rats. In the present study, rat liver microsomal drug-metabolizing enzymes were assayed after 10 days oral administration with 40 mumol ABZ/kg per day. The activities of 4-nitroanisole O-demethylase, benzo [a] pyrene hydroxylase, 7-ethoxycoumarin O-deethylase, and 7-ethoxyresorufin O-deethylase increased 6-, 7-, 8-, and 30-fold, respectively. By immunoblotting an increase in cytochrome P-448 was observed. UDP-glucuronosyltransferase (GT) type 1 activities (1-naphthol, 7-hydroxycoumarin, 4-nitrophenol, and 4-methylumbelliferone) were significantly higher than in control microsomes (3- to 4-fold), while GT type 2 activities and bilirubin-GT remained unchanged. Microsomal epoxide hydrolase (benzo [a] pyrene oxide) increased 2-fold. Microsomal gamma-glutamyltransferase activity was unchanged. The in vivo SO-ABZ plasma level was decreased when the SO2-ABZ plasma level was increased. In vitro sulfoxidation and sulfonation were, however, unchanged. Although a range of imidazole derivatives, including benzimidazole itself, were commonly reported as inhibitors of monooxygenase activities, ABZ behaved as an inducer of cytochrome P-448, GT1, and epoxide hydrolase. |
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