他达拉非片在中国健康受试者体内的生物等效性及药动学研究OA

AIM To evaluate the bioequivalence,pharmacokinetics,and safety of 2 tadalafil tablets in healthy Chinese subjects.METHODS A single-center,randomized,open,two-period,self-crossover trial was designed with 24 healthy subjects in the fasted and fed groups.For each group,a single oral dose of 20 mg was administered per period for both the test and reference formulations.The concentration of tadalafil in plasma at multiple time points following administration was measured by liquid chromatography tandem mass spectrometry(LC-MS/MS).WinNonlin 8.3 was used to conduct the non-compartmental analysis for pharmacokinetic(PK)parameters.SAS 9.4 software was used to perform analysis of variance(ANOVA)on the log-transformed Cmax and AUC of the test and reference formulations.The geometric mean ratios and their 90％confidence intervals were calculated for bioequivalence comparison,with the equivalence interval set at 80.00％to 125.00％.Safety was assessed by the incidence of adverse events(AEs).RESULTS The main PK parameters of tadalafil in the fasted group for the test and reference formulations were as follows:Cmax were(382.12±108.00)μg·L-1 and(372.04±88.54)μg·L-1;AUC0-t were(9 913.95±3 663.76)μg·h·L-1 and(9 895.98±3 944.39)μg·h·L-1;AUC0-∞ were(10 176.21±3 661.42)μg·h·L-1 and(10 079.40±3 825.68)μg·h·L-1.The main PK parameters of tadalafil in the fed group for the test formulation and reference formulation were as follows:Cmax were(515.29±86.36)μg·L-1 and(501.43±100.30)μg·L-1;AUC0-t were(11 713.21±2 954.11)μg·h·L-1 and(11 794.72±4 187.48)μg·h·L-1;AUC0-∞ were(12 552.20±3 619.53)μg·h·L-1 and(12 723.88±5 047.66)μg·h·L-1.The 90％confidence intervals for the Cmax,AUC0-t and AUC0-∞ were all within the equivalence interval of 80％-125％for both the test and reference formulations.Both formulations demonstrated bioequivalence.No serious adverse events occurred across any groups.CONCLUSION The 2 tadalafil tablets demonstrate bioequivalence under both fasted and fed conditions and exhibit good safety profiles.