阿司匹林缓释胶囊在健康志愿者体内的生物等效性

Bioequivalence Study of Aspirin Sustained-release Capsules in Healthy Volunteers

目的:研究阿司匹林缓释胶囊的人体相对生物利用度和生物等效性。方法:健康志愿者20名,用随机双交叉试验方法,单剂量及多剂量po试验及对照制剂162.5和150 mg,剂间间隔为2周。用高效液相色谱法测定阿司匹林体内活性代谢产物水杨酸的血浆药物浓度,计算两者的药代动力学参数及相对生物利用度,并进行生物等效件评价。结果:单剂量口服试验及对照制剂的C_(max)分别为2.77±0.68和2.62±0.83 mg L;t_(max)分别为2.87±2.52和3.48±2.09 h;t_(1/2)分别为11.07±4.46和12.41±5.03 h;AUC_(0-60)分别为62.50±16.06和57.36±14.70 mg·h·L^(-1);AUC_(O-inf)分别为65.50±18.71和61.33±17.44 mg·h·L^(-1);相对生物利用度为(110.9±19.1)％。多剂量口服实验制剂和参比制剂达到稳态后的C_(min)分别为0.72±0.26和0.78±0.16mg·L^(-1);C_(max)分别为4.78±1.48和4.49±1.45 mg·L^(-1);t_(1/2)分别为 9.06±1.50和8.87±1.39 h;AUC^(SS)分别为64.22±14.71和61.79±13.22 mg·h·L^(-1);DF分别为1.44±0.43和1.37±0.48;相对生物利用度为(108.9±35.5)％。结论:两制剂在单剂量和多剂量条件下具有生物等效性。

OBJECTIVE: To study the bioequivalence and relative bioavailability of aspirin sustained-release capsules. METHODS: A single oral dose( 162.5 mg of test, 150 mg of reference) and multiple oral doses(162.5 mg of test, 150 mg of reference for six days) were given to 20 healthy volunteers in a randomised crossover study. The concentrations of salicylic acid(SA, the metabolite of aspirin) in plasma were determined by HPLC method. The pharmacokinetic parameters were calculated and the bioavailability and bioequivalence of two formulations were evaluated. RESULTS: After a single dose, the pharmacokinetics parameters for SA were as follows: C_(max) were 2.77± 0.68 and 2.62±0.83 mg · L^(-1); t_(1/2) were 11.07± 4.46 and 12.41±5.03 h; t_(max) were 2.87±2.52 and 3.48±2.09 h; AUC_((0-60)) were 62.50±16.06 and 57.36±14.70 mg · h· L^(-1); AUC_((0-inf)) 65.50±18.71 and 61.33±17.45 mg ·h · L^(-1) for tested formulation and reference formulation, respectively. The relative bioavailability was (110.9±19.1)%. Following the multiple dose, C_(min) in the steady state were 0.72±0.26 and 0.78±0.16 mg ·L^(-1), C_(max) 4.78±1.48 mg/L and 4.49±1.45 mg/L, t_(1/2) were 9.06±1.50 and 8.87±1.39 h; AUC^(ss)64.22±14.71 and 61.79± 13.22 mg ·h· L^(-1), DF were 1.44±0.43 and 1.37±0.48 The relative bioavailability (108.9±35.5)%. CONCLUSION: The results showed that the two formulations were bioequivalence.