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目的:研究二氢吡啶类钙离子拮抗药(DHPs)中非洛地平、尼卡地平、乐卡地平、硝苯地平对CYP3A4酶活性抑制作用大小,为临床了解DHPs发生药物相互作用的几率大小提供理论基础。方法:采用探针药物法,将经80 mg·kg-1·d-1地塞米松诱导3 d的SD雌性大鼠分为阴性对照组、阳性对照组、4种DHPs实验组,每组6只。氨苯砜为探针底物,HPLC法为检测手段,数据通过Win Non Lin药动学分析软件进行模型拟合处理,并通过配对t检验进行统计学分析。结果:阴性对照组与四种DHPs组、阳性对照组氨苯砜的AUC0-24、CL/F值比较有统计学意义(P<0.05)。4种DHPs对氨苯砜的代谢抑制作用大小分别为硝苯地平>尼卡地平>乐卡地平>非洛地平,但差异无统计学意义(P>0.05)。而统计学结果显示阳性对照组、4种DHPs组与阴性对照组的Cmax比较,差异无统计学意义(P>0.05)。结论:虽然不同DHPs对CYP3A4存在不同的抑制作用,但差异在体内表现并不显著,对于非主要通过CYP3A4代谢的共服药物不会产生影响。
OBJECTIVE: To study the inhibitory effect of felodipine, nicardipine, lercanidipine and nifedipine on the activity of CYP3A4 in dihydropyridine calcium-ion antagonists (DHPs), and provide a basis for investigating the probability of drug-drug interaction in DHPs Theoretical basis. Methods: Female SD rats induced by 80 mg · kg-1 · d-1 dexamethasone for 3 days were divided into negative control group, positive control group and 4 DHPs groups only. Dapsone was used as the probe substrate, and HPLC method was used as the detection method. The data were fitted by Win Non Lin pharmacokinetic analysis software and analyzed by paired t-test. Results: The AUC0-24 and CL / F values of dapsone in the positive control group were significantly different from those in the four DHPs groups (P <0.05). The metabolic inhibition of dapsone by four DHPs were nifedipine> nicardipine> lercanidipine> felodipine, but the difference was not statistically significant (P> 0.05). The statistical results show that positive control group, 4 DHPs group and negative control group Cmax, the difference was not statistically significant (P> 0.05). CONCLUSIONS: Although different DHPs have different inhibitory effects on CYP3A4, the differences are not significant in vivo and do not affect co-administration of drugs that are not primarily metabolized by CYP3A4.