Metabolism of antipyrine and sulphadimidine in dwarf goats: effects of the enzyme-inducing agents phenobarbital, troleandomycin and rifampicin.
1. Antipyrine (AP) and sulphadimidine (SDD) plasma elimination and metabolite formation were studied in dwarf goats before and after treatment with phenobarbital (PB), triacetyloleandomycin (TAO), and rifampicin (RIF). 2. PB treatment significantly increased AP plasma clearance in both male and female goats. With SDD, only male goats were studied, which showed a significant increase of SDD plasma clearance following PB treatment. 3. After PB treatment, partial clearance values of four AP metabolites, 3-hydroxymethylantipyrine (HMA), norantipyrine (NORA), 4-hydroxyantipyrine (OHA) and 4,4'-dihydroxyantipyrine (DOHA), were significantly increased. This induction effect was different for the individual metabolites and also showed sex-dependency. 4. In PB-induced male goats the formation of the hydroxylated SDD metabolites, 6-hydroxymethyl-SDD and 5-hydroxy-SDD, was significantly increased. 5. After TAO treatment, female goats showed a slightly reduced AP plasma clearance and a decreased partial clearance of two AP metabolites, HMA and DOHA. There was no effect on SDD plasma elimination or metabolite excretion. 6. In male goats, RIF had no effect on plasma elimination of AP and SDD. With SDD, it decreased the urinary excretion of the unchanged drug and its N4-acetylated metabolite. 7. Induction/inhibition studies of drug metabolism in food-producing animal species are desirable to gain more insight into the regulation of enzymes involved in the metabolism of xenobiotics.
Natsuhori
M
M
Department of Veterinary Basic Sciences, University of Utrecht, The Netherlands.
Witkamp
R F
RF
Van 't Klooster
G A
GA
Van Miert
A S
AS
D000818:Animals; D000983:Antipyrine / Q000378:metabolism* / Q000493:pharmacokinetics; D001711:Biotransformation; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006041:Goats; D008297:Male; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology*; D013418:Sulfamethazine / Q000378:metabolism* / Q000493:pharmacokinetics; D014217:Troleandomycin / Q000494:pharmacology*
D013418:Sulfamethazine; D014217:Troleandomycin; D000983:Antipyrine; D012293:Rifampin; D010634:Phenobarbital