丹酚酸B在冠心病血瘀证患者中的药代动力学研究  

Pharmacokinetic study of lithospermata B on patients with blood-stasis syndrome of CHD

作　　者：张颖[1] 高蕊[1] 刘建勋[1] 王书臣[1] 

机构地区：[1]中国中医科学院西苑医院,北京100091

出　　处：《中药药理与临床》2010年第6期22-24,共3页Pharmacology and Clinics of Chinese Materia Medica

基　　金：科技部科技重大专项2004AA2Z3762和2009ZX09502-006课题资助

摘　　要：目的:研究丹参主要活性成分丹酚酸B(lithospermate B,mlB)在冠心病血瘀证患者体内的药代特征,为临床合理用药提供依据;通过与健康人药代数据的比较,揭示中医证型对药物动态的影响。方法:采用高效液相-电化学方法检测静脉滴注200mg丹参多酚酸盐注射液后,不同时间点血浆中mlB的血药浓度。采用Winnolin软件计算药代参数。SPSS软件比较冠心病血瘀证患者和健康受试者体内的药代参数。结果:所建立的分析方法具有特异性,准确度、精密度以及回收率都满足临床药代试验要求。冠心病血瘀证患者的曲线下面积(AUC(0-t))、平均滞留时间(MRT(0-t))、末端消除半衰期(t1/2z)、清除率(CLz)和分布容积(Vz)分别为10.7±5.58 mg/h.L、22.14±8.78 h、1.71±0.78 h、0.31±0.12 L/kg.h和0.78±0.51 L/kg,与健康人相比,冠心病血瘀证人的t1/2z显著减小,Vz虽然下降较大,但是由于较大的标准差,没有达到统计学上的显著性差别。其他药代参数在两组间没有差别。结论:mlB在血瘀证患者中的药代特征与健康受试者明显不同,血液循环功能的下降可能是造成药物分布减少,进而使半衰期缩短的病理机制。对于冠心病血瘀证患者可适当提高剂量、延长滴注时间或增加给药次数。Object ：In order to provide data of preparations containing lithospermata B（mlB）,an major active constituent of Danshen（丹参）,for its rational administration in clinics,and reveal the effect of TCM syndrome on pharmacokinetic fate of mlB,its pharmacokinetic profile was investigated on patients with blood-stasis syndrome of CHD（coronary artery disease）.and subsequently compared to that of healthy subjects.Method：A HPLC method with electrochemical detection（ECD） was developed to quantify the mlB in plasma after iv infusion of Salvianolate at 200mg dose.The pharmacokinetic parameter was calculated by Winnolin software using non-compartment analysis and comparison between two groups was tested by SPSS.Result：The analysis method was verified to be of the satisfied specificity,linearity,accuracy and precision.The parameters of AUC（0-t）,MRT（0-t）,t1/2z,CLz and Vz of patients were calculated as 10.7±5.58 mg/h·L、22.14±8.78 h、1.71±0.78 h、0.31±0.12 L/kg·h and 0.78±0.51 L/kg respectively.Compared to healthy subjects,the t1/2z was decreased significantly（P0.05） on patients.The Vz of patients was only half of the healthy subjects but no statistic difference was observed owing to the large deviation of individual Vz.Conclusion：The pharmacokinetic property of mlB in patients with blood-stasis syndrome of CHD is different from that of healthy subjects.The declined function of blood circulation under blood-stasis syndrome might be the reason of lower distribution volume and therefore caused the shorter half-life time of mlB on patients.An enhanced dosage,prolonged infusion time or shorten dosing interval would be the reasonable adjustment for patients with blood-stasis syndrome of CHD to maintain a suitable plasma level of mlB.

关 键 词：丹酚酸B 丹参多酚酸盐注射液 冠心病血瘀证 药代动力学 HPLC-ECD 

分 类 号：R285[医药卫生—中药学]