重组CYP3A46细胞微粒体体外药物代谢动力学分析

    In vitro analysis on pharmacokinetics by microsomes from recombinant CYP3A46 cell lines

    • 摘要: 通过对巴马小型猪CYP3A46 重组细胞微粒体体外药物代谢动力学特征比较分析,为巴马小型猪应用于临床前药理试验提供科学依据。分析重组CYP3A4、CYP3A46 细胞微粒体药物代谢动力学参数Vmax、Km(S50)、Clint 及IC50 均表明:CYP3A46 的硝苯地平、睾酮的代谢活性及酮康唑的抑制活性均比较接近CYP3A4(P>0.05),CYP3A46 是否是CYP3A4 的同源酶需要进一步研究确定。

       

      Abstract: The objective was to provide a scientific basis for the use of Bama miniature pig as a clinlical experimental animal by comparatively analyzing pharmacokinetic parameters of microsomes from stably expressing recombinant cell lines human CYP3A4 and Sus scrofa CYP3A46-Bama. The results demonstrated that the metabolic activities of microsomes from recombiant cell lines CYP3A46 to nifedipine and testosterone were very close to that of CYP3A4 based on the analysis of pharmacokinetic parameters Vmax, Km(S50) and Clint, so were the inhibitory activities of ketoconazole to CYP3A46 and CYP3A46 based on IC50s. Further researches should do to determine whether human CYP3A4 and Sus scrofa CYP3A46 were homologous enzymes.

       

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