依帕司他单剂量与多剂量给药的药代动力学研究  

Pharmacokinetics of Epalrestat After a Single and Multiple Oral Dose in Healthy Volunteers

作　　者：余自成[1] 杨婉花[1] 刘长义[2] 周玉琢[3] 张芳华[1] 陈秀莲[1] 

机构地区：[1]上海第二医科大学瑞金医院临床药理研究室,上海200025 [2]国家医药管理局天津药物研究院,天津300193 [3]江苏扬子江药业集团,泰州225421

出　　处：《中国临床药理学杂志》2000年第3期205-208,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：对10例健康志愿者按50mg单剂量和多剂量口服依帕司他（Epalrestat）后的药代动力学进行了研究。多剂量给药方案按q8h共服药10次。应用高效液相色谱一紫外检测方法测定依帕司他血药浓度。血药浓度数据用3p87药代动力学软件处理，按两室模型拟合并求算药代动力学参数。单剂量给药后的药代动力学参数分别为：Tmax2.25±0．95h，Cmax4104.91±849．87·g·L-1，AUC13016．6±2865.4μg·h·L－1，T1/2β1.11±0.35h。多剂量给药达稳态后的药代动力学参数分别为：Tmax2．00±1.03h，Cmin146．24±54．50μg·L-1，Cmax4769．99±897.86μg·L-1，Cavg1789.03±416.04μg·L-1，AUC14689.5±3472.3μg·h·L-1，T1/2β1.21±0.26h。依帕司他在人体内的吸收速度和消除速度不随连续给药变化，按50mg，q8h方案给药，药物在体内基本没有蓄积，性别对药代动力学参数没有影响。The pharmacokinetics of epalrestat were investigated after single and multipleoral doses of 50mg of epalrestat in 10 healthy volunteers(male 5, female 5). Multiple-dose regimens used 8-hour dosing intervals for 10 doses. Plasma epalrestat concentrationswere measured using high-performance liquid chromatography. The concentration-timecurves of epalrestat were fitted to a two-compartment open model.The pharmacokineticparameters obtained from the single-dose study were as follows:Tmax2.25±0．95h，Cmax 4104.91±849．87·g·L-1，AUC 13016．6±2865.4μg·h·L－1，T1/2β1.11±0.35hThe steady-state pharmacokinetic parameters were:Tmax2．00±1.03 h， Cmin 146．24 ± 54．50μg·L-1， Cmax 4769．99 ± 897.86μg·L-1， Cavg1789.03±416.04μg·L-1，AUC 14689.5±3472.3μg·h·L-1，T1/2β1.21±0.26h。 The absorption rate and elimination rate ofepalrestat were not changed after multiple oral administration. There was no accumulationof drug in plasma to be found after the repeated administration with the 50mg, q.8hregimen and no difference in pharmacokinetics of epalrestat in male and female volunteerswas observed. Lender has no effect on its pharmacokinetics.

关 键 词：依帕司他 药代动力学 给药方法 

分 类 号：R969.1[医药卫生—药理学]