SEX-DIFFERENCES IN THE DISPOSITION OF ALBENDAZOLE METABOLITES IN SHEEP

Sex differences in the disposition of albendazole metabolites in sheep after oral administration of 20 mg/kg of netobimin have been studied. Some kinetic parameters of both metabolites show statistical differen ces between sexes; the sulphoxide and sulphone t(1/2 beta) and MRT wer e lower in male animals than in females. Peak concentrations and AUC o f sulphone metabolites were higher in males suggesting a greater oxida tion rate compared with females. Urine excretion of albendazole metabo lites, sulphoxide, sulphone, and amino sulphone appeared to be greater in female sheep than in males, mainly the sulphoxide metabolite. Thes e differences between sexes can be caused by male sexual hormones, bec ause testosterone and progesterone can induce or inhibit the microsoma l Cytochrome P450 metabolism. Plasma protein-binding of albendazole su lphoxide and albendazole sulphone has been studied between male and fe male sheep, also their binding to sheep albumin and globulins. Both al bendazole metabolites readily bind to sheep albumin and globulins. Mal e animals show a significantly lower binding of albendazole metabolite s than females. These differences could be responsible for the non-est erified fatty acids (NEFA) present in the plasma. Males have significa ntly higher plasma levels of NEFA than females and which may compete w ith albumin for binding to albendazole metabolites. (C) 1998 Elsevier Science B.V. All rights reserved.