盐酸特比萘芬片在中国健康受试者的生物等效性研究

Bioequivalence of terbinafine hydrochloride tablets in Chinese healthy subjects

目的研究2种盐酸特比萘芬片在中国健康受试者体内的生物等效性。方法空腹试验和餐后试验各入组40例健康受试者,随机、开放、双周期、双交叉单剂量口服盐酸特比萘芬片受试制剂和参比制剂125 mg,用液相色谱串联质谱(LC-MS/MS)法测定给药后不同时间点特比萘芬的血药浓度。用Phoenix WinNonlin^(■)8.1软件计算药代动力学参数,考察两制剂生物等效性。结果空腹试验中受试制剂和参比制剂特比萘芬的药代动力学参数C_(max)分别为(644.17±274.24)和(663.98±274.76)ng·mL^(-1),AUC_(0-t)分别为(2440.59±1034.53)和(2521.69±1056.85)ng·mL^(-1)·h,AUC_(0-∞)分别为(2668.83±1153.59)和(2797.24±1234.36)ng·mL^(-1)·h。餐后试验中受试制剂和参比制剂特比萘芬的药代动力学参数C_(max)分别为(735.70±266.51)和(705.16±236.93)ng·mL^(-1),AUC_(0-t)分别为(3762.86±1203.85)和(3718.49±1262.15)ng·mL^(-1)·h,AUC_(0-∞)分别为(4159.11±1400.04)和(4174.91±1690.98)ng·mL^(-1)·h。受试制剂与参比制剂C_(max)、AUC_(0-t)和AUC_(0-∞)几何均数比值的90%置信区间均在85.12%~111.81%内,表明盐酸特比萘芬片受试制剂和参比制剂在空腹状态和餐后给药时均具有生物等效性。结论2种盐酸特比萘芬片在中国健康受试者体内具有生物等效性。

Objective To study the bioequivalence of two terbinafine hydrochloride tablets in healthy Chinese subjects.Methods The fasting test and the fed test each enrolled 40 healthy subjects in a random,open,two-period,double-crossover single-dose oral terbinafine hydrochloride tablets test and reference preparations 125 mg.The plasma concentrations of terbinafine at different time points were determined by liquid chromatography tandem mass spectrometry(LC-MS/MS).The pharmacokinetic parameters were calculated and the bioequivalence was compared by Phoenix WinNonlin^(■)8.1 program.Results The pharmacokinetic parameters for test and reference preparations in fasting condition were as follows:terbinafine C_(max) were(644.17±274.24)and(663.98±274.76)ng·mL^(-1),AUC_(0-t) were(2440.59±1034.53)and(2521.69±1056.85)ng·mL^(-1)·h,AUC_(0-∞)were(2668.83±1153.59)and(2797.24±1234.36)ng·mL^(-1)·h,respectively.The pharmacokinetic parameters for test and reference preparations in fed condition were as follows:terbinafine C_(max) were(735.70±266.51)and(705.16±236.93)ng·mL^(-1),AUC_(0-t) were(3762.86±1203.85)and(3718.49±1262.15)ng·mL^(-1)·h,AUC_(0-∞)were(4159.11±1400.04)and(4174.91±1690.98)ng·mL^(-1)·h,respectively.The 90%confidence intervals of the geometric mean ratios of C_(max),AUC_(0-t),AUC_(0-∞)for the test preparation and the reference preparation were all between 85.12%and 111.81%.It shows that the test preparation and reference preparation of terbinafine hydrochloride tablets are bioequivalent both in fasting or fed condition.Conclusion The two terbinafine hydrochlorothiazide tablets are bioequivalent in Chinese healthy subjects.