咪达那新片在中国健康受试者生物等效性研究

Bioequivalence of imidafenacin tablets in Chinese healthy subjects

目的研究咪达那新片仿制药与原研药在中国健康受试者中单剂量空腹和餐后条件下给药的生物等效性。方法采用单中心、随机、开放、单次给药、两制剂、两周期交叉试验设计,共纳入60例(空腹试验30例,餐后试验30例)成年男性和女性受试者随机交叉给药。分别单次口服受试制剂和参比制剂0.1 mg,用液相色谱串联质谱法(LC/MS/MS)测定血浆中咪达那新的浓度。用WinNonlin6.4软件计算主要药代动力学参数。结果空腹组的咪达那新片受试制剂和参比制剂主要药代动力学参数:C_(max)分别为(736.33±252.16)和(661.86±57.97) ng·L^(-1),AUC_(0-t)分别为(2 981.00±1 040.70)和(2 661.00±605.60) ng·L^(-1)·h^(-1),AUC_(0-∞)分别为(3 106.00±1 036.50)和(2785.00±611.70)ng·L^(-1)·h^(-1),T_(1/2)分别为1.00 (0.50,3.00)和1.00 (0.75,2.50) h,T_(1/2)分别为(3.61±1.10)和(3.41±0.83)h。餐后组的咪达那新片受试制剂和参比制剂主要药代动力学参数:C_(max)分别为(669.94±237.48)和(703.80±245.48) ng·L^(-1),AUC_(0-t)分别为(3 369.00±845.30)和(3 239.00±734.10) ng·L^(-1)·h^(-1),AUC_(0-∞)分别为(3 486.00±860.20)和(3 351.00±39.10)ng·L^(-1)·h^(-1),T_(1/2)分别为2.00(0.75, 5.02)和1.50(0.50, 5.00)h,T_(1/2)分别为(4.14±1.12)和(3.81±1.03)h。在空腹及餐后条件下,受试制剂与参比制剂主要药代动力学参数的90%置信区间均在80.00%-125.00%。结论在空腹及餐后条件下,中国健康成年志愿者单次口服咪达那新片仿制药与原研药具有生物等效性。

Objective To study the bioequivalence of manyfacturer and original imidafenacin tablets in Chinese healthy subjects after single dose under fasting and postprandial conditions. Methods A single-center, random, open, single-dose, two-preparations, double-period, crossover study was adopted. A total of 60 healthy adult male and female subjects(30 cases of fasting test and 30 cases of postprandial test) were included in the random crossover administration. Single oral dose 0.1 mg of test and reference were taken, respectively. Plasma concentration of imidafenacin in plasma was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS). The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 6.4 software. Results The main pharmacokinetic parameters of the test and reference preparations of imidafenacin tablets in the fasting groupwere as follows: C_(max)were(736.33±252.16) and(661.86±57.97) ng·L^(-1), AUC_(0-t) were( 2 981. 00 ± 1 040. 70) and( 2 661. 00 ± 605. 60) ng·L^(-1)·h^(-1),AUC_(0-∞) were( 3 106. 00 ± 1 036. 50) and( 2 785. 00 ±611. 70) ng · L^(-1)· h^(-1),T_(1/2)were 1. 00( 0. 50,3. 00) and 1. 00( 0. 75,2. 50) h,t;were( 3. 61 ±1. 10) and( 3. 41 ±0. 83) h. The main pharmacokinetic parameters of the test and reference preparations of imidafenacin tablets in the postprandial groupwere as follows: C_(max)were( 669. 94 ± 237. 48) and( 703. 80 ± 245. 48)ng·L^(-1);AUC_(0-t) were( 3 369. 00 ± 845. 30) and( 3 239. 00 ± 734. 10) ng·L^(-1)·h^(-1), AUC_(0-∞) were( 3 486. 00 ±860. 20) and( 3 351. 00 ±39. 10) ng·L^(-1)·h^(-1),T_(1/2)were 2. 00( 0. 75,5. 02) and 1. 50( 0. 50,5. 00) h,T_(1/2) were( 4. 14 ± 1. 12) and( 3. 81 ± 1. 03) h. Under fasting and postprandial conditions,the 90% confidence intervals of the main pharmacokinetic parameters of the test and reference preparations are both 80. 00% -125. 00%. Conclusion Under fasting and postprandial conditions,a single oral dose of manyfacturer and original imidafenacin tablets in Chinese healthy adult volunteers showed bioequivalence.