丙泊酚注射液在中国健康受试者的药代动力学和药效学  

Pharmacokinetics/pharmacodynamics evaluation of two injection formulations of propofol in healthy Chinese volunteers

作　　者：曹婉雯[1] 许重远[1] 黄鹏翔[2] 陈渊成[3] 郑萍[4] 古妙宁[5] 肖金仿[5] 郑航[4] 马安德 

机构地区：[1]南方医科大学南方医院国家药物临床试验机构,广州510515 [2]南方医科大学南方医院药学院,广州510515 [3]复旦大学附属华山医院抗生素研究所,上海200040 [4]南方医科大学南方医院Ⅰ期研究室,广州510515 [5]南方医科大学南方医院麻醉科,广州510515 [6]南方医科大学卫生检测中心,广州510515

出　　处：《中国临床药理学杂志》2014年第5期421-424,435,共5页The Chinese Journal of Clinical Pharmacology

基　　金：广州市科技计划基金资助项目(2013J4500041);南方医科大学南方医院院长基金青年基金资助项目(2011C019)

摘　　要：目的评价丙泊酚中/长链脂肪乳注射液在中国男性健康受试者中的药代动力学和药效学。方法随机、双盲、两阶段两药的自身交叉阳性对照试验设计。20名中国男性健康受试者单次静脉注射试验药物或参比药物2 mg·kg-1,用HPLC-MS/MS法测定血药浓度,比较2药物的药代动力学(PK)和药效学(PD)参数差异;测定脑电双频谱指数(BIS);并观察试验期间不良事件。结果 20名受试者均完成试验。丙泊酚符合三室模型,单次静脉注射试验药物或参比药物后,药代动力学参数如下:tmax分别为(2.25±0.44),(2.25±0.44)min;t1/2分别为(1.94±0.45),(1.89±0.36)h;cmax分别为(6.53±1.91),(6.41±1.77)μg·mL-1;AUC0-t分别为(1.53±0.24),(1.57±0.26)μg·mL-1·h。试验药物和参比药物的相对生物利用度(F)为(101.10±12.06)%。给药后最小BIS值出现时间(tmin-BIS)分别为(2.90±0.79),(2.95±0.69)min,BISAUC(0-25 min)分别为1904.2±129.9,1914.1±170.7。试验期间未发生严重不良事件。结论丙泊酚在中国男性健康受试者中的药代动力学具有消除快的特点,给药后BIS值变化迅速,且与血药浓度变化保持较好的相关性。Objective To evaluate the pharmacokinetics and pharmaco- dynamics and to assess the therapeutic equivalence between two injection formulations of propofol medium and long chain fat emulsion injection in healthy male Chinese volunteers. Methods Twenty healthy male Chi- nese volunteers were enrolled in a randomized, double - blinded, and crossover study. Each subject was intravenously injected a single dose of 2 mg ~ kg-1 test or reference formulation. The plasma concentration of propofol was determined by a validated HPLC -MS/MS method. Phar- macodynamics （PD） parameters, and bispectral index （BIS） were recor- ded by EEG monitor. In addition, the onset time of emergences from hyp- nosis were observed. Results Twenty subjects accomplished the trial. The propofol belonged to three -compartment model in vivo. After a sin- gle dose of propofol or reference formulation, the pharmacokinetics pa- rameters of propofol were as follows ： tmax were （2. 25 ± 0. 44） , （2. 25 ± 0. 44） min; tl/2 were （ 1.94 ± 0. 45 ） , （ 1.89 ± 0. 36 ） h; Cmax were （6.53±1.91）, （6.41 ±1.77） p,g · mL-1; AUC0-t, were （1.534 ± 0. 242）, （1. 571 ±0. 259） μg · mL-1·h. The relative bioavailability of test to reference formulation was （ 101.10 ± 12.06）%. The appearing time of minimum BIS value were as follows： tm~,_Bis were （2. 90 ±0. 79）, （2.95 ±0.69） min,BIS AUC（0-25min）were 1904.2 ± 129.9, 1914. 1 ± 170. 7. No serious adverse events occurred in the trial.Conclusion The elimination of propofol in healthy male Chinese volunteers is quick. There are rapid changes in BIS value after injection and a good correlation is maintained with plasma concentration changes.

关 键 词：丙泊酚注射液 药代动力学 药效学 生物等效性 

分 类 号：R969.1[医药卫生—药理学] R972.4[医药卫生—药学]