Gyrd-Hansen N, Friis C, Nielsen P, Rasmussen F
Acta Pharmacol Toxicol (Copenh). 1984 Nov;55(5):402-9. doi: 10.1111/j.1600-0773.1984.tb02002.x.
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.
在1日龄（A组）、8日龄（B组）和60日龄（C组）仔猪上进行了体内和体外实验，研究甲氧苄啶（TMP）的代谢情况。在体内研究中，仔猪接受静脉注射14C-甲氧苄啶。然后收集尿液3小时，之后处死动物。在收集期间，A组、B组和C组分别有13%、24%和40%的剂量经尿液排出。测定了血浆、肝脏、肾脏、尿液和胆汁中的甲氧苄啶及其以下代谢物：代谢物1和4、次要代谢物以及结合物。结果表明，新生仔猪氧化TMP的能力较弱，而与葡萄糖醛酸和硫酸盐结合的能力似乎略高。在接下来的8周内，氧化和结合能力均显著增加。肝脏和肾脏的微粒体部分用于TMP的体外代谢研究。在肾脏制剂中未显示出代谢活性。新生仔猪肝脏中仅可检测到氧化去甲基化，但随着年龄增长显著增加。三组肝脏制剂中均发生了代谢物4的葡萄糖醛酸化，但C组的速率最高。发现体内和体外代谢能力的发展在质量上相似。
