Comparative sulphoxidation of albendazole by sheep and cattle liver microsomes and the inhibitory effect of methimazole.
1. The comparative rates of oxidation of the benzimidazole anthelmintic, albendazole (ABZ), by sheep and cattle liver microsomes, and inhibition by the antithyroid compound methimazole (MTZ) were investigated. 2. ABZ was oxidized to its sulphoxide metabolite (ABZSO) in an NADPH concentration-dependent reaction. Heat inactivation of the microsomal flavin-containing mono-oxygenase system significantly decreased the NADPH consumption of microsomes in the presence of ABZ, MTZ and thiourea. 3. Oxidation of ABZ, MTZ and thiourea by sheep liver microsomes consumed significantly more NADPH than oxidation by cattle microsomes. 4. Neither the pro-ABZ drug, netobimin, nor the ABZ sulphone metabolite (ABZSO2) was modified by incubation with either sheep or cattle liver microsomes. 5. ABZSO was oxidized into ABZSO2 at a very slow rate and only when a high microsomal protein concentration was used. 6. MTZ was a potent inhibitor of ABZ sulphoxidation and the inhibition was significantly lower in cattle than in sheep microsomes.
Institute of Parasitology, McGill University, Ste-Anne de Bellevue, QC, Canada.
C E
CE
Lanusse
B
B
Nare
R K
RK
Prichard
D015766:Albendazole / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors; D066298:In Vitro Techniques; D008713:Methimazole / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000037:antagonists & inhibitors; D012756:Sheep; D013454:Sulfoxides / Q000378:metabolism; D013890:Thiourea / Q000494:pharmacology
D065607:Cytochrome P-450 Enzyme Inhibitors; D013454:Sulfoxides; D009249:NADP; D008713:Methimazole; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D015766:Albendazole; D013890:Thiourea; C027186:albendazole sulfoxide