进口和国产丙泊酚中长链脂肪乳剂注射液单次静注的药效学对比研究

Comparative Study of the Pharmacodynamics of Single Intravenous Injection of Medium-chain and Long-chain Triglytriglycerids Lipid Emulsion of Imported vs Domestic Propofol

[目的]以进口丙泊酚中长链脂肪乳剂注射液（竟安）为对照,验证国产同剂型丙泊酚注射液在健康志愿者单次注射的临床药物效应与药物安全性.[方法]本试验采用单中心、随机、单盲、两阶段两药的自身交叉阳性对照的设计方法,每个受试者分两阶段静脉注射两药,期间洗脱期为7d;20名健康成年男性志愿者随机分成A、B两组每组10名,A组第一阶段注射试验药（国产丙泊酚中长链脂肪乳剂注射液）,第二阶段注射对照药,B组则相反.按2mg/kg的剂量静脉注入两药后,连续记录BIS值,意识消失时间（t-LOC）、意识恢复时间（t-ROC）、意识消失持续时间（d-LOC） 、最小BIS值出现时间（t-BISmin）.监护受试者的各项生命体征,包括心率（HR）、无创收缩压（SBP）、无创舒张压（DBP）、呼吸频率（RR）、脉搏血氧饱和度（SpO2）、呼吸末二氧化碳分压 （PETCO2）;在志愿者意识清醒后用VAS表评定注射痛,并在试验全程及试验后观察两药的不良反应.[结果]A、B两组两阶段交叉实验后对照药和试药药的BIS值除A组试验药与对照药的最小BIS值比较有统计学差异外（P=0.034）,其余各项BIS值两药均无统计学差异（P〉0.05）;两药t-LOC、t-ROC、d-LOC、t-BISmin的比较均无统计学差异（P〉0.05）;给药后各项生命体征的变化无统计学差异;两药注射痛的VAS评分无统计学差异（P〉0.05）;在不良反应方面无显著差异.[结论]在健康志愿者单次注射国产丙泊酚中长链脂肪乳剂注射液和竟安注射液后,两者具有相似的临床药物效应和药物安全性.

[Objective] To verify the clinical drug effect and safety of single intravenous injection of medium-chain and long-chain triglytriglycerids lipid emulsion injection of domestic propofol in healthy volunteers through compared with the same imported propofol injection（Jingan ）. [Methods]A single-center, randomized, single-blind, two-stage and self-crossover positive controlled trial was adopted in this study. Each subject received intravenous injection with two drugs in two stages. The elution duration was 7 days. Twenty healthy male volunteers were randomly divided into group A and group B with 10 volunteers in each. Group A was injected with test drug（medium-chain and long-chain triglytriglyeerids lipid emulsion injection of domestic propofol） in phase I and control drug in phase II, while the medication of group B was the opposite. BIS value, the time of the loss of conseiousness（t-LOC）, the time of recovery of consciousness（t-ROC）, the duration of loss of consciousness（d-LOC） and the emergence time of minimal BIS value（t-BISmin） were re- corded continuously after intravenous bolus of two drugs 2mg/kg. Vital signs including heart rate（HR）, noninvasive systolic blood pressure（SBP）, diastolic blood pressure（DBP）, respiratory rate（RR）, pulse oxygen saturation（SpO2 ） and end-tidal pressure of carbon dioxide（PgrCO2 ） in subjects were monitored. Injection pain was evaluated by visual analog scale（VAS） after recovery of consciousness in subjects. The adverse reactions of two drugs were observed during and after the trial. [Results] There was significant difference in minimal BIS value between test drug and control drug in group A after two-stage crossover experiment（ P =0. 034）. There was no significant difference in BIS value except minimal BIS value between test drug and control drug in two groups（ P 〉0.05）. There was no significant difference in t-LOC, t-ROC, d-LOC and t-BISmin between test drug and control drug（ P〉0.05）. The VAS score of injection pain and adverse reactions showed no significant difference between test drug and control drug（ P 〉0.05）. [Conclusion] The clinical drug effect and safety of single intravenous injection of medium-chain and long-chain triglytriglycerids lipid emulsion injection of domestic propofol in healthy volunteers are similar to those of Jingan iniection.