肝病患者药物代谢酶细胞色素P450酶1A2、多态性N-乙酰化酶、黄嘌呤氧化酶活性的变化  

The study of activity change of drug metabolic enzymes CYP1A2,NAT2 and XO in patients with liver disease

作　　者：刘丽娟[1] 李军[1] 郭瑞臣[2] 张世玲[2] 

机构地区：[1]山东省立医院,山东济南250021 [2]山东医科大学,山东济南250021

出　　处：《中国医院药学杂志》2000年第4期212-214,共3页Chinese Journal of Hospital Pharmacy

摘　　要：目的 :以咖啡因为代谢探针 ,研究肝病患者咖啡因代谢物比值 (caffeinemetaboliteratios ,CMRs)的变化 ,探讨CMRs作为药物代谢酶细胞色素P45 0酶 1A2 (CYP1A2 )、多态性N 乙酰基转移酶 (NAT2 )、黄嘌呤氧化酶 (XO)的活性指标 ,用于调整某些药物用药方案的可行性。方法 :选择健康受试者 30例 ,慢性肝病受试者 30例。采用高效液相色谱 (HPLC)法测定受试者尿液中 5种咖啡因主要代谢物浓度 ,计算特定的CMRs。对研究结果进行统计学处理 ,对健康受试组与肝病受试组、慢性活动性肝炎受试组、代偿期肝硬化受试组的CMRs数据分别进行t检验 ,分别考察组间数据的差异性 ,判断肝病患者药物代谢酶CYP1A2、NAT2、XO的酶活性变化。结果 :肝病患者包括慢性活动性肝炎或代偿期肝硬化患者CYP1A2、NAT2活性显著降低(P <0 .0 5 ) ;而XO活性无显著性变化 (P >0 .0 5 )。结论 :可为临床调整经去甲基化。OBJECTIVE:Caffine was used as a metabolic probe to study the change of caffeine metabolite ratios(CMRs) represen ting the activities of drug metabolic enzymes cytochrome P4501A2(CYP1A2),polymorphic N acetyltransferase(NAT2) and xanthine oxidase(XO) in patients with liver disease.The feasibility of CMRs as indicators of three enzymes above to adjusting dosage regimen of some drug was explored.METHODS:Thirty healthy subjects and thirty patients with liver disease were voluntarily enrolled in the test.The main five caffeine metabolites in urine sample were measured by high performance liquid chromatography and the specific CMRs were calculated.The test results were analysed statisticaly.Difference between the healthy participants and subjects with liver disease(chronic active hepatitis or compensed cirrhotics) was made by t test to determine the change of activities of CYP1A2,NAT2 and XO.RESULTS:The results showed that the activities of CYP1A2 and NAT2 in subjects with liver disease including chronic active hepatitis and compensated cirrhotic reduced significantly( P < 0.05 ),but XO activity with no change at all( P > 0.05 ).CONCLUSIONS:This result provided the reference for adjusting dosage regimen of the drug subjected to the metabolism of demethylation and acetylation for clinic.

关 键 词：肝病 咖啡因 药物代谢酶 CYP1A2 NAT2 XO 

分 类 号：R575[医药卫生—消化系统] R969[医药卫生—内科学]