奥美拉唑、兰索拉唑和泮托拉唑对药物代谢酶CYP1A2活性影响的研究

Study on the effect of omeprazole,lansoprazole and pantoprazole on the activity of drugmetabolism enzyme CYP1A2 in human

目的探讨奥美拉唑、兰索拉唑和泮托拉唑对药物代谢酶CYP1A2活性的影响,预测奥美拉唑、兰索拉唑和泮托拉唑与常用药物的相互作用,以指导临床医师合理用药。方法以咖啡因作为药物代谢酶CYP1A2的探针药物,以反相高效液相梯度洗脱法测定90名受试者分别服用奥美拉唑、兰索拉唑和泮托拉唑前后尿液内咖啡因4种主要代谢产物的相对含量,采用代谢物的比率评价药物代谢酶CYP1A2活性的变化。结果服用奥美拉唑、兰索拉唑和泮托拉唑3种质子泵抑制剂前CYP1A2平均活性分别为5.36±2.10,3.64±1.92,3.37±1.22;服药后活性分别为5.83±2.37,4.02±2.17,3.50±1.23,服药前后药物代谢酶CYP1A2活性无统计学意义(P>0.05)。结论服用治疗剂量的奥美拉唑、兰索拉唑和泮托拉唑7d后,药物代谢酶CYP1A2活性无明显影响,奥美拉唑、兰索拉唑和泮托拉唑可能不会影响与之合用的需经CYP1A2代谢的药物疗效。

Objective To investigate the effect of omeprazole, lansoprazole and pantoprazole on the activity of drug metabolism enzyme CYP1A2 in human and to forecast the drug-drug interaction with commonly used drugs so as to instruct clinician to prescribe rationally. Methods In ninety volunteers, caffeine was used as a metabolic probe for CYP1A2. Before and after omeprazole, lansoprazole and pantoprazole administration, urine samples were collected. The contents of four major metabolites of caffeine in the urine were determined by RP-HPLC, then evaluated the activity change of CYP1A2 by the ratio of metabolites of caffeine. Results It was found that before omeprazole, lansoprazole and pantoprazole administration the average activity of CYP1A2 were 5.36 ± 2.10, 3.64 ± 1.92, 3.37 ± 1.22, and the average activity of CYP1A2 were 5.83 ± 2.37, 4.02 ± 2.17, 3.50 ± 1.23 after 7 days treatment. There were no statistical significance between before treatment and after treatment （P〉0.05）. Condusion Omeprazole, lansoprazole and pantoprazole have no influence on CYP1A2 after 7 days treatment, so omeprazole, lansoprazole and pantoprazole do not metabolized by CYP 1A2. modify the efficacy of drugs taken simultaneously which are