己酮可可碱缓释片在中国健康人体内生物等效性研究OA

Objective To study the pharmacokinetic characteristics of pentoxifylline sustained release tablets in healthy volunteers in China and further evaluate their bioequivalence.Methods According to a two-sequence and two-cycle completely repeated crossover design,84 healthy volunteers were divided into 42 fasting and 42 postprandial healty subjects.Each cycle used one of the test preparation(T,400 mg)or the reference preparation(R,400 mg)respectively.The concentrations of pentoxifylline and its active metabolites M1 and M5 in plasma were determined using a methodologically confirmed UPLC-MS/MS method.Finally,pharmacokinetic software was used to calculate the pharmacokinetic parameters and evaluate the bioequivalence.Results The Cmax,AUC0-t,and AUC0-∞ of pentoxifyline of the test and refer-ence formulations in the fasting trial were(251.46±99.96)and(273.96±105.79)ng/mL,(1539.80±733.54)and(1578.30±914.33)h·ng/mL,(1744.06±872.07)and(1736.29±974.11)h·ng/mL,respectively.The Cmax,AUC0-t,and AUC0-∞ of pentoxify-line of the test and reference formulations in the postprandial trial were(412.76±312.27)and(445.86±326.21)ng/mL,(1932.72±978.78)and(1956.93±882.17)h·ng/mL,(1997.97±994.27)and(2027.07±870.19)h·ng/mL,respectively.The 90％confi-dence interval for the least squares geometric mean ratio of pharmacokinetic parameters fell within the judgment range of 80％-125％.Con-clusion The test and reference formulations of pentoxifylline sustained-release tablets have bioequivalence in fasting and postprandial trials.