丙泊酚乳状注射液在中国健康受试者中的生物等效性研究  

Bioequivalence study of propofol injectable emulsion in healthy Chinese volunteers

作　　者：孙守飞 李文馨 董江涛 张静 杨艳皎 刘瑞霞 SUN Shou-fei;LI Wen-xin;DONG Jiang-tao;ZHANG Jing;YANG Yan-jiao;LIU Rui-xia(Shandong Cisen Fodu Pharmaceutical Co.,Ltd.,Jining 272500,Shandong Province,China;Shandong Institute for Food and Drug Control,Jinan 250101,Shandong Province,China;Cisen Pharmaceutical Co.,Ltd.,Jining 272073,Shandong Province,China;Shandong Nuochen Beitong Pharmaceutical Technology Co.,Ltd.,Jining 272073,Shandong Province,China;Henan Zhonghui Hosptial,Zhengzhou 4450000,Henan Province,China)

机构地区：[1]山东辰欣佛都药业股份有限公司,山东济宁272500 [2]山东省食品药品检验研究院,山东济南250101 [3]辰欣药业股份有限公司,山东济宁272073 [4]山东诺辰贝通医药科技有限公司,山东济宁272073 [5]河南(郑州)中汇心血管病医院Ⅰ期研究中心,河南郑州450000

出　　处：《中国临床药理学杂志》2025年第1期86-90,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价丙泊酚乳状注射液在中国健康受试者中的药代动力学和药效学,并考察丙泊酚脂肪乳注射液受试制剂和参比制剂在健康人体的生物等效性。方法本研究用单剂量、两周期、双交叉空腹试验设计。入组的32例健康受试者以30μg·kg-1·min-1的速度缓慢静脉输注受试制剂或参比制剂30 min。用高效液相色谱串联质谱(HPLC-MS/MS)法测定血浆中丙泊酚的浓度,计算2种制剂的药代动力学参数;测定脑电双频指数(BIS),计算2种制剂的药效动力学参数;记录试验期间发生的不良事件。结果31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:C_(max)分别为(660.87±110.25)和(683.13±125.75)ng·mL^(-1),AUC_(0-t)分别为(473.50±86.03)和(478.40±80.25)h·ng·mL^(-1),AUC_(0-∞)分别为(500.45±96.49)和(507.84±88.00)h·ng·mL^(-1),t_(max)分别为0.47(0.25,0.53)和0.50(0.40,0.54)h,t_(1/2)分别为(2.97±1.74)和(3.08±1.82)h。31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92.64%~101.39%、96.43%~101.00%和95.67%~100.70%。受试制剂和参比制剂的主要药效动力学参数如下:BISmin分别为75.94±13.66和74.39±12.32,BISAUC 0-60 min分别为5569.85±182.78和5575.68±166.19,T-BISmin分别为23.00和29.00 min。本研究无严重不良事件发生。结论2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 injectable emulsion,and to assess the bioequivalence of test and reference formulations in healthy Chinese adult volunteers.Methods Thirty-two 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 avalidated high performance liquid chromatographyy-tandem masssspectrometery(HPLC-MS/MS)method.The PK parameters of the two preparations were calculated.Bispectral index(BIS)was measured to calculate the PD parameters of two formulations.Adverse events during the trial were recorded.Results Thirty-one volunteers were included in the pharmacokinetic parameter set.The mean values of PK parameters of test andreference formulations were as follows:C_(max) were(660.87±110.25)and(683.13±125.75)ng·mL^(-1);AUC_(0-t) were(473.50±86.03)and(478.40±80.25)h·ng·mL^(-1);AUC_(0-∞)were(500.45±96.49)and(507.84±88.00)h·ng·mL^(-1);t_(max) were 0.47(0.25,0.53)and 0.50(0.40,0.54)h;t_(1/2) were(2.97±1.74)and(3.08±1.82)h.Thirty-one 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 92.64%-101.39%,96.43%,-101.00%,95.67%-100.70%,respectively.The mean values of PD parameters of test and reference formulations were as follows:BIS_(min) were(75.94±13.66)and(74.39±12.32);BIS_(AUC 0-60 min) were 5569.85±182.78 and 5575.68±166.19;T-BIS_(min) were 23.00 and 29.00 min,respectively.There were no serious adverse events.Conclusion Two formulations of propofol injectable emulsion were bioequivalent and both of them exhibited good safety.

关 键 词：丙泊酚乳状注射液 药代动力学 药效学 生物等效性 

分 类 号：R971.2[医药卫生—药品]