【摘 要】
：
Minipigs represent a good animal model because of the physiological and anatomical similarities they share with humans.Three cytochrome P450 (CYP) 3A isozymes,CYP3A22,3A29,and 3A46,have recently been
【机 构】
：
Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-
【出 处】
：
2016华南实验动物科学国际研讨会、第三届实验小型猪国际论坛暨广东·九州实验动物学术交流会
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Minipigs represent a good animal model because of the physiological and anatomical similarities they share with humans.Three cytochrome P450 (CYP) 3A isozymes,CYP3A22,3A29,and 3A46,have recently been reported to be expressed in Bama minipigs which have limited data relating to their metabolic characteristics.In the present study,Bama minipig CYP3A22,3A29,and 3A46 were recombinantly expressed and their metabolic manners were compared to those of human CYP3A4 and CYP3A5,and also human and Bama minipig liver microsomes.The results indicated Bama minipigs and human CYP3A enzymes showed similar metabolic kinetics and metabolite profiles using testosterone,midazolam,and nifedipine as substrates.However,the differences in amino acid sequences change the elimination velocity and metabolic preference of CYP3A enzymes to their substrates.It was demonstrated that CYP3A29,3A4,and 3A5 were the most active enzymes for all reactions,while CYP3A46 was the least active enzyme.There exist substrate-dependent metabolism characteristics between human and Bama minipig CYP3A isoenzymes.
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