氮烯乙茶在大鼠、犬、猴肝亚细胞成分中的生物转化

目的:利用肝亚细胞成分研究I类抗癌新药氮烯乙茶的生物转化及其种属差异。方法:以高效液相色谱法检测肝9 000 ×g 上清液(S-9) 和微粒体中氮烯乙茶及其代谢产物的浓度。结果:大鼠、犬、猴肝S-9中氮烯乙茶的固有清除率(CL_int) 分别为14-9,10-4,30-4 μL·min^-1·mg^-1 protein,代谢产物为7-乙基-8-氨基茶碱(7-ethyl-8-aminotheophylline,EAT),氮烯乙茶在肝的生物转化部位在微粒体。结论:预计氮烯乙茶在生物转化途径上的种属差异较小;肝亚细胞成分是研究药物代谢及种属差异的较好体外模型。

BIOTRANSFORMATION OF ETHEOFAZINE IN HEPATIC SUBCELLULAR FRACTIONS FROM RAT, DOG AND MONKEY

AIM: To study the biotransformation and its species differences of etheofazine, a new anticancer drug, in hepatic subcellular fractions. METHODS: The concentration of etheofazine and its metabolite in hepatic 9 000×g supernatant fractions (S-9) and microsomes were determined with HPLC method. RESULTS: Enzyme kinetics studies of etheofazine in rat, dog and monkey liver S-9 indicated that the in vitro liver intrinsic clearance was 14.9, 10.4 and 30.4 μL·min^-1 ·mg^-1 protein, respectively. The metabolite formed in hepatic microsome was shown to be 7 ethyl 8 aminotheophylline(EAT). CONCLUSION: The insignificant species differences in metabolic profile of etheofazine can be anticipated. The results suggest that hepatic subcellular fractions are useful as in vitro models for species difference study.