论文部分内容阅读
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。
OBJECTIVE: To evaluate the efficacy of propofol / long-chain fat emulsion injection (Anhui Fengyuan) and reference formulation propofol medium / long-chain fat emulsion injection (Beijing Fresenius) in Beagle dogs Bioequivalence and Pharmacokinetic Studies. Methods: Eight Beagle dogs were injected with 4 mg / kg propofol medium / long-chain fat emulsion intravenously by double-cycle intravenous injection, and the elution period was one week. The blood concentration of propofol in Beagle dogs was determined by LC-MS method. The data were processed by DAS 3.2.8 software. The bioequivalence of propofol medium / long-chain fat emulsion injection was analyzed. Sex and pharmacokinetics. Results: The elimination half-life t_ (1/2) of propofol medium / long-chain fat emulsion injection was (46.652 ± 12.239) min and (44.637 ± 11.874) min, respectively. (max) were (4.784 ± 1.215) mg / L and (4.802 ± 1.111) mg / L, respectively; peak time t max was 1 min and 1 min respectively; AUC_ (0-t) (39.212 ± 18.710) mg · min · L -1 and (41.846 ± 15.293) mg · min · L -1, respectively; the area under the curve AUC_ (0-∞) were (43.146 ± 19.308) mg · Min · L -1 and (45.264 ± 15.599) mg · min · L -1, respectively. MRT was (24.273 ± 8.998) min and (25.743 ± 10.706) min respectively. The relative bioavailability, F, was (110.2 ± 12.0)% as compared to that of the propofol emulsion for injection. Conclusion: The plasma concentration of propofol in Beagle dogs can be determined rapidly, accurately and simply by LC-MS method. After logarithmic conversion, C_ (max) and AUC were analyzed by multivariate analysis of variance, double unilateral t-test and (1-2α)% confidence interval method. The results showed that the two formulations were bioequivalent.