Metabolism of trimethoprim in neonatal and young pigs: comparative in vivo and in vitro studies.
Metabolism of trimethoprim (TMP) was investigated in in vivo and in vitro experiments on 1 day (group A), 8 days (group B), and 60 days (group C) old piglets. In the in vivo studies piglets received an intravenous injection of 14C-trimethoprim. Urine was then collected for 3 hours after which the animals were killed. During the collection period 13, 24, and 40% of the dose was excreted in the urine in group A, B, and C, respectively. Trimethoprim and the following metabolites: Metabolite 1 and 4, minor metabolites, and conjugates were determined in plasma, liver, kidney, urine, and bile. The results show that newborn piglets have little capacity for oxidation of TMP while the ability to conjugate with glucuronic acid and sulfate seems somewhat higher. During the following 8 weeks a marked increase in the oxidative as well as conjugative potential took place. The microsomal fractions of liver and kidney were used for the in vitro metabolism studies of TMP. No metabolic activity could be demonstrated in the kidney preparations. Oxidative demethylation was just detectable in livers from the newborn piglets but increased considerably with age. Glucuronidation of metabolite 4 took place in the liver preparations from all three groups but at the highest rate in group C. The development in metabolic capacity was found to be qualitatively similar in vivo and in vitro.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D001835:Body Weight; D005260:Female; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009929:Organ Size; D010084:Oxidation-Reduction; D013552:Swine / Q000378:metabolism*; D014018:Tissue Distribution; D014295:Trimethoprim / Q000097:blood / Q000378:metabolism* / Q000652:urine
D014295:Trimethoprim