酮洛芬择时释药片Beagle犬体内的生物等效性

Bioequivalence of ketoprofen time-controlled release tablets in Beagle dogs

目的:研究酮洛芬择时释药片(受试制剂)和酮洛芬胶囊(参比制剂)在Beagle犬体内的药动学特征和生物等效性。方法:采用双周期双交叉试验,每只Beagle犬口服受试制剂和参比制剂,于相应时间点取静脉血检测酮洛芬血药浓度。采用DAS 2.1.1软件分别计算2种制剂的药动学参数,并计算受试制剂的相对生物利用度。通过统计学分析比较2种制剂的生物等效性。结果:受试制剂和参比制剂的主要药动学参数分别为t1/2(4.28±1.59)h和(5.90±2.33)h,Cmax(61.36±2.37)μg·mL^-1和(67.59±10.72)μg·mL^-1,tmax(5.83±0.61)h和(2.04±0.19)h,tlag(3.46±0.25)h和(0.46±0.22)h,AUC0-t(341.16±19.09)μg·h·mL^-1和(355.93±51.82)μg·h·mL^-1,AUC0-∞(354.29±19.91)μg·h·mL^-1和(416.77±42.49)μg·h·mL^-1,受试制剂的相对生物利用度为85.01%。结论:受试制剂和参比制剂的AUC0-t、Cmax是生物等效性的,但在tmax、tlag生物不等效。受试制剂在一定的时滞(约3.458h)后释药,符合择时释药制剂的释药要求。

OBJECTIVE To study the pharmacokinetic characteristics and bioequivalence of ketoprofen time-controlled release tablets(test preparation)and ketoprofen capsules(reference preparation)were evaluated.METHODS A two-period cross over experiment design was conducted.Each Beagle dog was administered with a single oral dose of test or reference preparation,and the blood was respectively taken at the corresponding time to test the plasma concentration.DAS 2.1.1 software was respectively used to calculate the pharmacokinetic parameters of the two preparations.The relative bioavailability of the test preparation was calculated.The bioequivalence of the two formulations was compared by statistical analysis.RESULTS The main pharmacokinetics parameters for test and reference preparation were as follows:t1/2(4.28±1.59)and(5.90±2.33)h,Cmax(61.36±2.37)and(67.59±10.72) μg·mL^-1,tmax(5.83±0.61)and(2.04±0.19)h,tlag(3.46±0.25)and(0.46±0.22)h,AUC0-t (341.16±19.09)and(355.93±51.82)μg·h·mL^-1,AUC0-∞(354.29±19.91)and(416.77±42.49)μg·h·mL^-1.The relative bioavailability of the test preparation was 85.01%.CONCLUSION The two preparations were bioequivalent for AU C0-tand Cmax,but tmax and tlag were not bioequivalent.The test preparation was released after a certain time lag(about 3.458 h),which met the release requirements of the time-selective release preparation.