Watkins P J, Gorrod J W
Chelsea Department of Pharmacy, King's College London, University of London, UK.
Eur J Drug Metab Pharmacokinet. 1987 Oct-Dec;12(4):245-51. doi: 10.1007/BF03189907.
In vivo studies on the metabolism of trimethoprim have shown that N-oxidation to isomeric N-oxides occurs, with considerable inter-species variation in the proportion of each N-oxide excreted. No in vitro studies on the metabolism of trimethoprim have been reported to date. We now report a sensitive and specific HPLC method for the simultaneous determination of the isomeric N-oxides of trimethoprim. In vitro metabolic studies with hepatic microsomes from several animal species have been conducted. Optimum incubation conditions have been established and the use of potential metabolic inducers, activators and inhibitors has demonstrated that the N-oxidation of trimethoprim to its isomeric N-oxides is mediated via a cytochrome P450 dependent pathway.
对甲氧苄啶代谢的体内研究表明，会发生N-氧化生成异构体N-氧化物的情况，每种N-氧化物排泄比例存在相当大的种间差异。迄今为止，尚未有关于甲氧苄啶代谢的体外研究报道。我们现在报告一种灵敏且特异的HPLC方法，用于同时测定甲氧苄啶的异构体N-氧化物。我们已经开展了用几种动物物种的肝微粒体进行的体外代谢研究。已确定了最佳孵育条件，并且使用潜在的代谢诱导剂、激活剂和抑制剂已证明，甲氧苄啶向其异构体N-氧化物的N-氧化是通过细胞色素P450依赖性途径介导的。
