丙泊酚中/长链脂肪乳注射液在中国健康受试者中的生物等效性研究  

Bioequivalence study of propofol medium and long chain fat emulsion injection in healthy Chinese volunteers

作　　者：孔祥祯 刘帅兵[1] 刘瑞娟 杨志衡 俞海俊 艾艳秋[2] 田鑫[1] 张晓坚[1] KONG Xiang-zhen;LIU Shuai-bing;LIU Rui-juan;YANG Zhi-heng;YU Hai-jun;AI Yan-qiu;TIAN Xin;ZHANG Xiao-jian(Department of Pharmacy,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan Province,China;Department of Anesthesiology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan Province,China;Yangtze River Pharmaceutical Group,Taizhou 225300,Jiangsu Province,China)

机构地区：[1]郑州大学第一附属医院药学部,河南郑州450052 [2]郑州大学第一附属医院麻醉科,河南郑州450052 [3]扬子江药业集团有限公司,江苏泰州225300

出　　处：《中国临床药理学杂志》2022年第10期1111-1115,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家重大新药创制科技重大专项基金资助项目(2020ZX09201009)。

摘　　要：目的评价丙泊酚中/长链脂肪乳注射液在中国健康受试者中的药代动力学和药效学,并考察丙泊酚中/长链脂肪乳注射液受试和参比制剂在健康人体的生物等效性。方法本研究采用单剂量、两周期、双交叉空腹试验设计。入组的30例健康受试者按照30μg·kg^(-1)·min^(-1)的速度缓慢静脉滴注受试制剂或参比制剂30 min。用高效液相色谱-串联质谱法测定血浆中丙泊酚的浓度,计算两种制剂的药代动力学参数;测定脑电双频指数(BIS),计算两种制剂的药效学参数;记录试验期间的不良事件。结果29例受试者进入药代动力学参数集,受试制剂和参比制剂的主要药代动力学参数如下:T_(max)分别为0.46(0.41,0.53),0.46(0.41,0.53)h;C_(max)分别为(578±156),(592±143)ng·mL^(-1);AUC_(0-t)分别为(393.42±78.60),(425.74±92.98)h·ng·mL^(-1);AUC_(0-∞)分别为(416.96±80.49),(450.62±91.68)h·ng·mL^(-1);t_(1/2)分别为(3.14±1.38),(3.24±1.42)h。27例受试者进入生物等效性分析集,受试制剂与参比制剂主要药代动力学参数C_(max)、AUC_(0-t)、AUC_(0-∞)的几何均值比值的90%置信区间分别为86.81%~103.07%、84.28%~96.85%、84.85%~96.20%。受试制剂和参比制剂的主要药效学参数如下:BIS_(min)分别为70.93±9.73,70.15±11.03;BIS_(AUC0-30 min)分别为2313.41±353.34,2302.02±246.66;BIS_(AUC0-60 min)分别为4782.19±579.96,4702.06±451.48。受试制剂与参比制剂主要药效学参数BIS_(AUC0-30min)、BIS_(AUC0-60min)和BIS_(min)的几何均值比值的90%置信区间分别为95.02%~106.61%、98.52%~105.96%、95.98%~108.55%。本研究无严重不良事件发生。结论两种制剂在中国健康受试者中具有生物等效性,安全性良好。Objective To evaluate the pharmacokinetics(PK)and pharmacodynamics(PD)of propofol medium and long chain fat emulsion injection,and to assess the bioequivalence of test and reference formulations in healthy Chinese adult volunteers.Methods Thirty healthy Chinese adult volunteers were recruited and randomly assigned to a fasting,single-dose,two-period and double-crossover study.Propofol was given to eligible subjects at a speed of 30μg·kg^(-1)·min^(-1) for 30 min.The concentration of propofol in plasma was determined by a validated HPLC-MS/MS method.PD parameter,bispectral index(BIS)was measured and safety was also evaluated.Results Twenty-nine volunteers were included in the pharmacokinetic parameter set.The mean values of PK parameters of test and reference formulations were as follows:T_(max)0.46(0.41,0.53)and 0.46(0.41,0.53)h;C_(max)(578±156)and(592±143)ng·mL^(-1);AUC_(0-t)(393.42±78.60)and(425.74±92.98)h·ng·mL^(-1);AUC_(0-∞)(416.96±80.49)and(450.62±91.68)h·ng·mL^(-1);t1/2(3.14±1.38)and(3.24±1.42)h.Twenty-seven volunteers were included in the bioequivalence set.The 90%confidence intervals(CI)for the geometric mean ratios of C_(max),AUC_(0-t),AUC_(0-∞)were 86.81%-103.07%,84.28%-96.85%,84.85%-96.20%,respectively.The mean values of PD parameters of test and reference formulations were as follows:BISm in70.93±9.73,70.15±11.03;BISAUC_(0-30 min)2313.41±353.34,2302.02±246.66;BIS_(AUC0-60min)4782.19±579.96,4702.06±451.48.The 90%CI for the geometric mean ratios of BISm in,BISAUC_(0-30 min) and BIS_(AUC0-60min) were 95.02%-106.61%,98.52%-105.96%,95.98%-108.55%,respectively.There were no serious adverse events.Conclusion Two formulations of propofol medium and long chain fat emulsion injection were bioequivalent in PK and PD,and both of them exhibited good safety.

关 键 词：丙泊酚 药代动力学 药效学 生物等效性 

分 类 号：R971[医药卫生—药品]