【摘要】 [目的]研究普洛萨姆对大鼠肝微粒体细胞色素P4503A(CYP3A)酶动力学的影响。[方法]以CYP3A的探针反应,睾酮6β羟基化反应,来标记CYP3A的活性进行酶动力学体外研究。[结果]普洛萨姆浓度在0.1%~0.5%时,大鼠CYP3A活性略升高,但与对照组无显著差异(P>0.05);当浓度高于0.5%时,能抑制CYP3A活性,且抑制程度随浓度提高而加大。当浓度在0.8%~2%时,CYP3A活性有一定程度降低,但与对照组无显著差异(P>0.05),当浓度高于3%时,能观察到活性被抑制了约27.2%,与对照组比较有显著性差异(P<0.05),当浓度为5%时,抑制百分比已达42.3%。动力学研究表明,0.2%普洛萨姆对CYP3A动力学参数没有显著影响(P>0.05),但是2%普洛萨姆对CYP3A动力学参数有显著影响,Vmax、S50、CL均被低估,同时Hill系数被高估。[结论]普洛萨姆对大鼠CYP3A活性有浓度依赖性的影响,普洛萨姆在较高浓度能影响CYP3A酶的动力学性质。更多还原

【Abstract】 [Objective] To study the impact of poloxamers on the kinetics of CYP3A in rat liver microsomes. [Methods] The study of enzyme inhibition kinetics was conducted, utilizing testosterone 6β-hydroxylation as the indication for the activity of CYP3A in rat liver microsomes. [Results] In the range of 0.1%~0.5% polox- amers, there was a slight activation of CYP3A activity, but no significant difference was observed compared with control. When the concentration was more than 0.5%, poloxamers exhibited concentration-dependent in- hibition on CYP3A activity. In the range of 0.8%~2%, although the activity decreased, no significant inhibi- tion could be observed (P> 0. 05). However, significant inhibition was observed when the concentration of poloxamers exceeded 3% (P<0.05), and the CYP3A activity decreased by 42.3% at 5% polpxamers. The further kinetics study showed that 0. 2% poloxamers did not affect the kinetics parameters of CYP3A (P> 0.05), but 2% poloxamers significantly affected the evaluation of kinetics parameters of CYP3A (P<0.05), and resulted in underestimation of Vmax, S50, CL and overestimation of Hill coefficient. [Conclusions] Poloxam- ers may concentration-dependently influence CYP3A activity and the kinetics properties of CYP3A.更多还原