EFFECT OF GONADAL-HORMONES ON THE PLASMA-CLEARANCE AND METABOLITE FORMATION OF ANTIPYRINE IN THE DWARF GOAT

The effect of gonadal hormones on the plasma elimination and urinary m etabolite profile of antipyrine was studied in dwarf goats. Female goa ts were treated with testosterone and male goats were treated with 17b eta-oestradiol. Castrated males were treated with either testosterone or 17beta-oestradiol. Antipyrine (25 mg/kg, i.v.) was given both befor e and after the hormonal treatments. The effects of the hormonal statu s on the plasma elimination of the parent compound were not consistent . This was possibly due to the fact that formation of the main metabol ite of antipyrine in the goat, 4-hydroxy antipyrine (OHA), was not aff ected by sex or hormonal treatment. On the other hand, there were clea r effects of hormonal status on urinary excretion of the three other m etabolites. In females and castrated males testosterone suppressed the formation of norantipyrine (NORA), 3-hydroxymethylantipyrine (HMA) an d 4,4'-dihydroxyantipyrine (DOHA). Intact males produced smaller amoun ts of these metabolites than females. It is concluded that distinct xe nobiotic metabolizing pathways exist in the dwarf goat, which are infl uenced in their activity by gonadal hormones. This confirms previous f indings in rats and mice. The possibility that sex hormones influence drug metabolism in food-producing animals could have consequences for veterinary therapeutics and public health. This study also demonstrate s that, when using the antipyrine test for the assessment of hepatic d rug metabolism, it is very important to include the determination of m etabolites.