复方丹参滴丸对药物代谢酶CYP1A2，NAT2和XO活性影响的研究

The Study on the Effect of Compound Danshen Dripping Pills on the Activity of CYP1A2, NAT2, and XO

关键词:  复方丹参滴丸  咖啡因  高效液相色谱法  CYP1A2  NAT2  XO

Key words:  compound danshen dripping pills  caffeine  HPLC  cytochrome P450 1A2  N-acetyltransferase 2  xanthine oxidase

摘要:

目的探讨复方丹参滴丸对CYP1A2，NAT2和XO活性的影响，指导临床医师合理用药。方法以咖啡因作为探针药物，以HPLC测定受试者服用复方丹参滴丸前后尿液内咖啡因的5种主要代谢产物的相对含量，采用不同代谢物的比率分别评价 CYP1A2，NAT2和XO活性的变化。结果受试者用药前CYP1A2，NAT2和XO平均活性为4.20±1.54，0.36±0.12，0.33±0.05；服用复方丹参滴丸14 d后三者的平均活性为4.26±1.95，0.32±0.12，0.32±0.07；服用复方丹参滴丸28 d后三者的平均活性为4.35±1.26，0.30±0.11，0.31±0.04；服药14 d后CYP1A2，NAT2和XO活性无统计学差异；服药28 d后CYP1A2和NAT2活性无统计学差异，但XO的平均活性降低，且具有统计学差异。结论复方丹参滴丸对药物代谢酶CYP1A2和NAT2活性无明显影响。服用治疗剂量的复方丹参滴丸对XO活性具有抑制作用。

Abstract:

OBJECTIVE To investigate the effect of compound danshen dripping pills on the activity of CYP1A2, NAT2 and XO and to forecast the drug-drug interaction with it, so as to instruct clinician to prescribe rationally.METHODS In thirty volunteers , two-way cross design was used, caffeine was used as a metabolic probe for CYP1A2、NAT2,and XO, before and after compound danshen dripping pills administration, urine samples were collected. The contents of five major metabolites of caffeine in the urine were determined by RP-HPLC method. And then the activity change of CYP1A2，NAT2 and XO was evaluated by the ratio of metabolites of caffeine .RESULTS It was found that the average activity of CYP1A2,NAT2 and XO were 4.20±1.54，0.36±0.12，0.33±0.05 before treatment ,and 14 days after administration, the average activity of CYP1A2,NAT2 and XO were 4.26±1.95，0.32±0.12，0.32±0.07， and 28 days after administration, the average activity of CYP1A2,NAT2 and XO were 4.35±1.26，0.30±0.11，0.31±0.04. There was no statistical significance between before treatment and after taking medicine 14 days for CYP1A2,NAT2 and XO and also there was no statistical significance between before treatment and after taking medicine 28 days for CYP1A2 and NAT2. But there was statistical significance between before treatment and after taking medicine 28 days for XO. CONCLUSION Compound danshen dripping pills have no influence on CYP1A2 and NAT2,so compound danshen dripping pills do not modify the efficacy of drugs which metabolized by CYP1A2 and NAT2 taken simultaneously. But compound danshen dripping pills may modify the efficacy of drugs which metabolized by XO taken simultaneously.