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 differences between sexes; the sulphoxide and sulphone t1/2beta and MRT were lower in male animals than in females. Peak concentrations and AUC of sulphone metabolites were higher in males suggesting a greater oxidation rate compared with females. Urine excretion of albendazole metabolites, sulphoxide, sulphone, and amino sulphone appeared to be greater in female sheep than in males, mainly the sulphoxide metabolite. These differences between sexes can be caused by male sexual hormones, because testosterone and progesterone can induce or inhibit the microsomal Cytochrome P450 metabolism. Plasma protein-binding of albendazole sulphoxide and albendazole sulphone has been studied between male and female sheep, also their binding to sheep albumin and globulins. Both albendazole metabolites readily bind to sheep albumin and globulins. Male animals show a significantly lower binding of albendazole metabolites than females. These differences could be responsible for the non-esterified fatty acids (NEFA) present in the plasma. Males have significantly higher plasma levels of NEFA than females and which may compete with albumin for binding to albendazole metabolites.
Departament de Farmacologia i de Terapèutica, Facultat de Veterinària, Bellaterra, Spain. ivft0@cc.uab.es
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D000284:Administration, Oral; D015766:Albendazole / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000818:Animals; D000871:Anthelmintics / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006146:Guanidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D008297:Male; D011485:Protein Binding; D012709:Serum Albumin / Q000032:analysis / Q000378:metabolism; D012712:Serum Globulins / Q000032:analysis / Q000378:metabolism; D012727:Sex Characteristics; D012756:Sheep / Q000378:metabolism*
D000871:Anthelmintics; D005230:Fatty Acids, Nonesterified; D006146:Guanidines; D012709:Serum Albumin; D012712:Serum Globulins; D015766:Albendazole; C049626:netobimin