丹参注射液对家兔体内CYP1A2、CYP2D6和CYP3A4活性的影响

目的：用Cocktail探针药物法研究丹参注射液对家兔细胞色素P450亚型酶活性的影响。方法：将家兔随机分成四组,耳缘静脉注射给予丹参注射液,分低、中、高剂量三个实验组,空白对照组给予生理盐水。用HPLC法测定各组Cock-tail探针药物（咖啡因、美托洛尔和氨苯砜）的血药浓度,比较药时曲线及药代动力学参数的变化,评价各组细胞色素P450亚型酶的活性。结果：丹参注射液低、中、高剂量组CYP2D6的活性与对照组相比降低,具有统计学意义（P〈0.05或P〈0.01）;CYP1A2和CYP3A4的活性与对照组相比差异均无统计学意义。结论：丹参注射液对家兔CYP2D6有抑制作用,对CYP1A2和CYP3A4的影响不显著。提示临床应用丹参注射液时,应关注其对CYP2D6的抑制作用,避免联合用药引发CYP2D6介导的药物相互作用,促进临床安全合理用药。

Effects of Danshen Injection on the activity of rabbit CYP1A2,CYP2D6 and CYP3A4 in vivo

AIM：To evaluate the effects of Danshen Injection on rabbit cytochrome P450 （CYP450） activity by Cocktail probe drugs. METHODS： Male rabbits were randomly divided into three test groups and one control group. The test groups were treated with Danshen Injection （i.v.） at three dosages （low, midst and high dosage）, and the control group was treated with physiological saline. The plasma concentrations of probe drugs（caffeine,metoprolol and dapsone） were determined by HPLC. Effects of Danshen Injection on CYP450 activity were observed by comparing the concentration-time curves and pharmacokinetic parameters of probe drugs. RESULTS：The three dosages of Danshen Injection inhibited the CYP2D6 activity（P0.05, or P0.01）, but had no effects on the activities of CYP1A2 and CYP3A4. CONCLUSION： Danshen Injection can inhibit CYP2D6 activity in rabbit, but has no effect on CYP1A2 and CYP3A4. When Danshen Injection is used in clinic, attention should be paid to the inhibition effect on CYP2D6 to avoid CYP2D6-mediated drug interaction, and to promote safe and rational drug use.