他达拉非片在健康男性受试者的生物等效性研究

Bioequivalence of tadalafil tablets in healthy male subjects

目的:研究2种他达拉非片在中国健康男性受试者中的生物等效性。方法:采用随机、开放、两周期、两序列、交叉设计,空腹和餐后试验各36名健康男性受试者单次口服他达拉非片(20 mg)试验制剂(T)与参比制剂(R),采用液相色谱-串联质谱(LC-MS/MS)法测定血浆中他达拉非的血药浓度,应用WinNonlin8.0软件计算药动学参数,SAS 9.4软件进行统计分析。结果:空腹试验中试验制剂与参比制剂他达拉非的主要药动学参数,C_(max)分别为(320±78)和(354±74)ng/mL,AUC_(0-t)分别为(8800±2650)和(8840±2560)ng·h·mL^(-1),AUC_(0-∞)分别为(9600±3250)和(9510±3170)ng·h·mL^(-1)。餐后试验中试验制剂与参比制剂他达拉非的主要药动学参数C_(max)分别为(466±90)和(442±71)ng/mL,AUC_(0-t)分别为(10000±3020)和(10200±2950)ng·h·mL^(-1),AUC_(0-∞)分别为(10700±3780)和(10900±3680)ng·h·mL^(-1)。空腹试验他达拉非受试制剂与参比制剂C_(max)、AUC_(0-t)和AUC_(0-∞)几何均数的比值(GMR)分别为88.68%、96.32%和97.43%,其90%置信区间(90%CI)分别为82.56%~95.24%、90.96%~101.99%和91.87%~103.33%;餐后试验他达拉非受试制剂与参比制剂C_(max)、AUC_(0-t)、AUC_(0-∞)的GMR分别为105.03%、98.27%和97.54%,其90%CI分别为100.49%~109.78%、92.48%~104.42%和91.60%~103.86%,均完全落在80.00%~125.00%之间。结论:两种他达拉非片剂具有生物等效性。

AIM:To study the bioequivalence of two tadalafil tablets in Chinese healthy male subjects.METHODS:A randomized,open-label,two-period,two-sequence,crossover study designing was adopted in the study.Thirty-six healthy male subjects were enrolled under fasting condition and fed condition,respectively.Each subject was given a single oral dose of tadalafil tablet(20 mg).The concentration of tadalafil in plasma was determined by LC-MS/MS.The pharmacokinetic parameters were calculated by WinNonlin 8.0 program,and statistical analysis was performed by using SAS 9.4 statistics software.RESULTS:Under fasting condition,the pharmacokinetic parameters of tadalafil of the test(T)and reference(R)preparation were as follows:C_(max) were(320±78)and(354±74)ng/mL,AUC_(0-t) were(8800±2650)and(8840±2560)ng·h·mL^(-1),AUC_(0-∞)were(9600±3250)and(9510±3170)ng·h·mL^(-1).Under fed condition,the pharmacokinetic parameters of T and R were as follows:C_(max) were(466±90)and(442±71)ng/mL,AUC_(0-t) were(10000±3020)and(10200±2950)ng·h·mL^(-1),AUC_(0-∞)were(10700±3780)and(10900±3680)ng·h·mL^(-1).Under fasting condition,the 90%confidence interval(90%CI)of C_(max),AUC_(0-t) and AUC_(0-∞)of tadalafil were 82.56%-95.24%,90.96%-101.99%and 91.87%-103.33%.Under fed condition,the 90%CI of C_(max),AUC_(0-t) and AUC_(0-∞)of tadalafil were 100.49%-109.78%,92.48%-104.42%and 91.60%-103.86%.All datas were in the area of 80.00%-125.00%.CONCLUSION:The two tadalafil tablets are bioequivalent.