赛洛多辛及其活性代谢物在中国健康男性受试者中的生物等效性研究

Bioequivalence studies of silodosin and its active metabolite in healthy Chinese male subjects

目的:研究国产制剂和原研制剂赛洛多辛及其活性代谢物的生物等效性。方法:86名受试者按随机两周期交叉试验设计单剂量口服受试制剂或参比制剂4 mg,高效液相色谱-串联质谱法(LC-MS/MS)测定血浆中赛洛多辛及其活性代谢物(KMD-3213G)的浓度,WinNonlin 8.0软件计算药动学参数并评价其生物等效性。结果:受试制剂和参比制剂主要药动学参数,空腹组赛洛多辛:C_(max)(32.8±14.2)和(34.5±18.2)μg·L^(-1),AUC_(0-∞)(132.49±42.32)和(146.80±61.29)μg·h·L^(-1),AUC_(0-∞)(135.96±42.31)和(150.52±61.37)μg·h·L^(-1);KMD-3213G:C_(max)(22.0±7.00)和(22.4±7.78)μg·L^(-1),AUC_(0-∞)(484.59±201.07)和(527.53±267.64)μg·h·L^(-1),AUC_(0-∞)(501.66±213.41)和(550.36±298.09)μg·h·L^(-1);餐后组赛洛多辛:C_(max)(26.7±10.2)和(27.0±11.6)μg·L^(-1),AUC_(0-∞)(137.80±47.27)和(137.59±48.94)μg·h·L^(-1),AUC_(0-∞)(143.99±46.92)和(142.12±48.67)μg·h·L^(-1);KMD-3213G:C_(max)(21.3±6.74)和(22.3±6.99)μg·L^(-1),AUC_(0-∞)(525.09±231.28)和(535.49±228.56)μg·h·L^(-1),AUC_(0-∞)(554.37±254.85)和(561.25±250.06)μg·h·L^(-1)。受试制剂与参比制剂主要药动学参数的90%CI均在80.00%~125.00%。结论:国产制剂与原研制剂赛洛多辛及其活性代谢物具有生物等效性。

OBJECTIVE To research the bioequivalence of silodosin and its active metabolite(KMD-3213 G) between the domestic and imported formulations.METHODS A singe oral dose of 4 mg the test or reference formulation was given to 86 subjects in a randomized two-period crossover study. The concentrations of silodosin and its active metabolite silodosin(KMD-3213 G) in plasma were determined by LC-MS/MS. The pharmacokinetic parameters were calculated by Phonenix WinNolin 8.0 and the bioequivablence was evaluated.RESULTS The main pharmacokinetic parameters of the test and reference formulations were as follows: silodosin under fasting condition: C_(max)were(32.8±14.2) and(34.5±18.2) μg·L^(-1), AUC_(0-∞)were(132.49±42.32) and(146.80±61.29) μg·h·L^(-1), AUC_(0-∞)were(135.96±42.31) and(150.52±61.37) μg·h·L^(-1);KMD-3213 G: C_(max)were(22.0±7.00) and(22.4±7.78) μg·L^(-1), AUC_(0-∞)were(484.59±201.07) and(527.53±267.64) μg·h·L^(-1), AUC_(0-∞)were(501.66±213.41) and(550.36±298.09)μg·h·L^(-1);silodosin under fed condition: C_(max)were(26.7±10.2) and(27.0±11.6) μg·L^(-1), AUC_(0-∞)were(137.80±47.27) and(137.59±48.94) μg·h·L^(-1), AUC_(0-∞)were(143.99±46.92) and(142.12±48.67) μg·h·L^(-1);KMD-3213 G: C_(max)were(21.3±6.74) and(22.3±6.99)μg·L^(-1), AUC_(0-∞)were(525.09±231.28) and(535.49±228.56)μg·h·L^(-1), AUC_(0-∞)were(554.37±254.85) and(561.25±250.06)μg·h·L^(-1). The 90% confidence intervals of the main pharmacokinetic parameters of the test and reference formulations were between 80.00% and 125.00%, which met the criteria for bioequivalence evaluation.CONCLUSION Silodosin and its active metabolite between the domestic and imported formulations are bioequivalent.