茶碱缓释干混悬剂在Beagle犬体内的药动学和生物等效性

Pharmacokinetics and Bioequivalence of Theophylline Sustained-Release Suspensions in Beagle Dogs

研究茶碱缓释干混悬剂(受试制剂)和茶碱缓释片(参比制剂)在Beagle犬体内的药动学和生物等效性。进行双周期交叉试验,每条Beagle犬单次口服给予受试或参比制剂200 mg。建立了HPLC法测定Beagle犬血浆中的茶碱,用非房室模型分析得到参比制剂与受试制剂的主要药动学参数,分别为cmax(9.75±1.91)和(8.94±0.86)μg/ml,tmax(2.58±0.92)和(2.67±0.82)h,AUC0→t(76.59±9.51)和(75.22±15.06)μg·ml-1·h,AUC0→∞(79.55±9.86)和(77.08±13.44)μg·ml-1·h,t1/2(3.19±0.95)和(3.18±0.63)h,MRT(5.80±0.55)和(6.08±0.83)h。统计分析结果表明茶碱缓释干混悬剂与市售茶碱缓释片生物等效。

The bioequivalence between theophylline sustained-release suspensions （test preparation） and theophylline sustained-release tablets （reference preparation） was evaluated. A two-period crossover study was conducted. Each Beagle dog was administered a single oral dose of test or reference preparation 200 mg. An HPLC method was established for the determination of plasma concentration, and the results were calculated by noncompartmental methods. The main pharmacokinetic parameters for test and reference preparations were as follows： Cmax （9.75±1.91） and （8.94± 0.86） μg/ml, tmax （2.58±0.92）and（2.67±0.82） h, AUC0→t （76.59±9.51）and （75.22±15.06） μg·ml^-1·h, AUC0→∞（79.55± 9.86）and（77.08±13.44） μg·ml^-1·h, t1/2 （3.19±0.95）and（3.18±0.63） h, MRT （5.80±0.55） and （6.08±0.83） h. The statistical analysis of the results showed that the two preparations were bioequivalent.