阿司达莫缓释片在健康人体的药代动力学和相对生物利用度

Pharmacokinetics and relative bioavailability of dipyridamole compound sustained release tablets in healthy volunteers

目的研究阿司达莫缓释片(抗血栓药)在健康人体的药代动力学。方法18例健康男性志愿者随机交叉口服受试制剂(阿司达莫缓释片)或参比制剂(含双嘧达莫片200mg与阿司匹林肠溶片25mg),用高效液相色谱-紫外法测定血浆中双嘧达莫与水杨酸浓度,经DAS软件计算相对生物利用度,并进行生物等效性评价。结果①单剂量受试与参比双嘧达莫:tmax分别为(3.89±0.47),(1.69±0.42)h;Cmax分别为(1.27±0.33),(2.17±0.75)μg·mL-1;t1/2分别为(8.40±1.92),(4.78±1.13)h;AUC0-t分别为(7.89±2.70),(8.36±3.41)μg·h·mL-1;AUC0-∞分别为(8.99±3.12),(8.56±3.50)μg·h·mL-1。受试与参比水杨酸:tmax分别为(2.11±0.53),(4.78±0.81)h;Cmax分别为(0.97±0.47),(0.95±0.48)μg·mL-1;t1/2分别为(4.22±0.68),(5.46±1.09)h;AUC0-t分别为(4.06±1.65),(3.98±1.73)μg·h·mL-1;AUC0-t分别为(4.06±1.65),(3.98±1.73)μg·h·mL-1;AUC0-∞分别为(4.13±1.65),(4.15±1.79)μg·h·mL-1。②多剂量受试与参比双嘧达莫:tmax分别为(3.94±0.80),(1.90±0.58)h;Cssmax分别为(1.23±0.38),(1.31±0.32)μg·mL-1;AUCss分别为(7.48±2.72),(7.73±2.62)μg·h·mL-1。单次给药后,生物利用度双嘧达莫为(97.2±16.7)%、水杨酸为(103.1±9.8)%;多次给药后,双嘧达莫的生物利用度为(96.7±13.4)%。结论2制剂在体内生物作用等效。

Objective To study pharmacokinetics and relative bioavailability of dipyridamole compound sustained release tablet in healthy male volunteers. Methods A single oral dose and multiple oral doses of 200 mg dipyridamole and 25 mg aspirin test or reference preparations were given to 18 healthy volunteers in a randomized cross - over design. Plasma concentration of dipyridamole and salicylic acid was determined by HPLC - UV method. The relative bioavailability and bioequivalence between two formulations were evaluated by DAS program. Results Main pharmacokinetic parameters were as following：After a single dose of test and reference preparation, dipyridamole ： tmax were （3.89±0.47）,（1.69±0.42）h;Cmax were （1.27±0.33）,（2.17±0.75）μg·mL^-1;t1/2 were （8.40±1.92）,（4.78±1.13）h;AUC0-t were （7.89±2.70）,（8.36±3.41）μg·h·mL^-1;AUC0-∞ were （8.99±3.12）,（8.56±3.50）μg·h·mL^-1, respectively ; salicylic acid ： tmax were （2.11±0.53）,（4.78±0.81）h;Cmax were （0.97±0.47）,（0.95±0.48）μg·mL^-1;t1/2 were （4.22±0.68）,（5.46±1.09）h;AUC0-t were （4.06±1.65）,（3.98±1.73）μg·h·mL^-1;AUC0-∞ were （4.13±1.65）,（4.15±1.79）μg·h·mL^-1, respectively. After multiple doses, dipyridamole ： tmax were （3.94±0.80）,（1.90±0.58）h;Cssmax were （1.23±0.38）,（1.31±0.32）μg·mL^-1;AUCss were （7.48±2.72）,（7.73±2.62）μ·h·mL^-1 , respectively. After a single dose, relative bioavailability of dipyridamole and salicylic acid were （97.2 ± 16.7） % and （ 103.1 ±9.8） % ,respeerively;after multiple doses,relative bioavailability of dipyridamole was （96.7 ± 13.4） %. Conclusion Test and reference formulations are bioequivalent.