摘要
目的:评价受试制剂丙泊酚中/长链脂肪乳注射液(安徽丰原)与参比制剂丙泊酚中/长链脂肪乳注射液(北京费森尤斯卡比)在Beagle犬内的生物等效性和药动学研究。方法:8只Beagle犬双周期交叉静脉推注丙泊酚中/长链脂肪乳注射液受试制剂和参比制剂4 mg/kg,洗脱期为一周。用LC-MS法测定丙泊酚在Beagle犬内的血药浓度用DAS 3.2.8软件进行数据处理,分析受试制剂和参比制剂丙泊酚中/长链脂肪乳注射液的生物等效性和药动学。结果:丙泊酚中/长链脂肪乳注射液参比制剂与受试制剂的消除相半衰期t_(1/2)分别为(46.652±12.239)min和(44.637±11.874)min;药峰浓度C_(max)分别为(4.784±1.215)mg/L和(4.802±1.111)mg/L;达峰时间t_(max)分别为1 min和1min;药时曲线下面积AUC_(0-t),分别为(39.212±18.710)mg·min·L^(-1)和(41.846±15.293)mg·min·L^(-1);曲线下面积AUC_(0-∞)分别为(43.146±19.308)mg·min·L^(-1)和(45.264±15.599)mg·min·L^(-1);MRT分别为(24.273±8.998)min和(25.743±10.706)min。与丙泊酚注射用乳剂参比制剂相比相对生物利用度F为(110.2±12.0)%。结论:采用LC-MS法能够快速、准确、简单地测定丙泊酚在Beagle犬内的血浆浓度。C_(max)和AUC经对数转换后进行多因数方差分析、双单侧t检验和(1-2α)%置信区间法,结果表明该两种制剂静脉注射具有生物等效性。
AIM：To evaluate the bioequivalence and pharmacokinetic of propofol in medium and long chain triglyceride emulsion injection（Anhui of Fengyuan and Fresenius Kabi of Beijing） in Beagle dogs.METHODS：A single intravenous injection doses of 4 mg/kg propofol in medium and long chain triglyceride emulsion injection（test and reference） were given to 8 beagle dogs.The study was a randomized,two-period and crossover design with 7-day wash out period.The concentrations of propofol in plasma were determined by LC-MS.With the aid of DAS 3.2.8,the bioequivalence and pharmacokinetic of the test and reference preparation were calculated by analysis of variance,two-one sided t-test and confidence interval（1- 2α）.RESULTS：The pharmacokinetic parameters of the two preparations were as follow;t（1/2） of the reference and test drug were（46.652±12.239） min and（44.637 ±11.874） min,C（max） were（4.784±1.215） and（4.802±1.111） mg/L,t（max） were 1min and 1 min,AUC（0t） were（39.212 ± 18.710）mg·min·L（-1） and（41.846 ± 15.293）mg·min·L（-1）,AUC（0-∞） were（43.146 ± 19.308）mg·min·L（-1） and（45.264± 15.599）mg·min·L（-1）,MRT were（24.273 ±8.998） min and（25.743± 10.706） min,respectively.Compared to the reference of propofol in medium and long chain triglyceride emulsion injection,the bioavailability of the formulation was（110.2±12.0）%.CONCLUSION：The method of LC-MS was rapid,accuracy and simple,which can be applied to determine the concentrations of propofol in beagle dugs.The test preparation was bioequivalence to the reference preparation.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2015年第11期1271-1276,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics
关键词
丙泊酚中/长链脂肪乳注射液
丙泊酚
LC-MS
生物等效性
药动学
propofol in medium and long chain triglyceride emulsion injection
propofol
LC-MS
bioequivalence
pharmacodynamics
