去氧孕烯炔雌醇片在中国汉族健康人体的生物等效性

发布时间：2019-04-08 08:54

【摘要】：目的评价去氧孕烯炔雌醇片受试制剂和参比制剂在中国汉族健康受试人体中的药动学特点和生物等效性。方法 22名中国汉族健康男性受试者单中心、开放、随机交叉给药,每位受试者分别给予受试制剂1片或参比制剂1片(每片含去氧孕烯0.15 mg和炔雌醇0.02 mg),清洗期为2周,采用高效液相-质谱联用法(HPLC-MS/MS)测定3-酮-去氧孕烯(3-K-DG),采用放射免疫法测定炔雌醇的血药浓度,利用WinNonlin软件进行统计分析受试制剂和参比制剂中3-K-DG和炔雌醇的主要药动学参数,并评价其生物等效性。结果受试制剂和参比制剂中3-K-DG的tmax分别为(1.50±0.44)、(1.75±0.36)h,cmax分别为(1.22±0.44)、(1.15±0.42)μg·L-1,AUC0-t分别为(27.19±12.13)、(26.13±10.72)μg·h·L-1,t1/2分别为(58.61±100.92)、(60.42±37.36)h。受试制剂和参比制剂中炔雌醇的tmax分别为(2.00±0.41)、(2.00±0.37)h,cmax分别为(147.73±18.66)、(147.77±18.34)ng·L-1,AUC0-t分别为(1 999.97±1 113.47)、(1 899.12±909.95)ng·h·L-1,t1/2分别为(19.47±12.19)、(19.22±9.34)h;受试制剂和参比制剂间各参数均无显著差异(P0.05);受试制剂中3-K-DG和炔雌醇的相对生物利用度分别为(104.07±32.78)%和(105.31±45.31)%(n=22)。结论建立的HPLC-MS/MS分析方法和放射免疫法准确灵敏,两种去氧孕烯炔雌醇片制剂生物等效。
[Abstract]:Aim to evaluate the pharmacokinetic characteristics and bioequivalence of doxyprogesterone estriol tablets and reference preparations in healthy volunteers of Han nationality in China. Methods 22 healthy male subjects of Han nationality in China were given single center, open, randomized cross-administration. Each subject was given one tablet or one tablet of reference preparation (containing 0.15 mg of deoxyprogesterone and 0.02 mg), of estradiol), respectively. The cleaning period was 2 weeks. High performance liquid chromatography-mass spectrometry (HPLC-MS/MS) was used to determine the concentration of 3-keto-deoxyprogesterone (3-K-DG), and radioimmunoassay was used to determine the plasma concentration of estradiol. The main pharmacokinetic parameters of 3-K-DG and estradiol in the tested and reference preparations were statistically analyzed by WinNonlin software, and their bioequivalence was evaluated. Results the tmax and c max of 3-K-DG were (1.50 卤0.44), (1.75 卤0.36) h and (1.22 卤0.44), (1.15 卤0.42) 渭 g 路L-1, respectively. The AUC0-t values were (27.19 卤12.13), (26.13 卤10.72) 渭 g 路h 路L-1 and (58.61 卤100.92), (60.42 卤37.36) h, respectively. The tmax, cmax and AUC0 were (2.00 卤0.41), (2.00 卤0.37) ng 路L-1, (147.73 卤18.66), (147.77 卤18.34) ng 路L-1 and (1 999.97 卤1 113.47), respectively. (1 899.12 卤909.95) ng 路h 路L-1, (19.47 卤12.19), (路h 路L-1) h, (19.47 卤12.19), (, 19.22 卤9.34) h, respectively. The relative bioavailability of 3-K-DG and estradiol were (104.07 卤32.78)% and (105.31 卤45.31)% (n = 22), respectively. Conclusion the established HPLC-MS/MS analysis method and radioimmunoassay are accurate and sensitive, and two kinds of deoxyprogesterone estriol tablets are bioequivalent.
【作者单位】：广东医学院药学院;上海市计划生育科学研究所生殖药理组国家人口计生委计划生育药具重点实验室;济宁医学院附属金乡人民医院临床药学室;复旦大学附属中山医院药物临床试验机构;
【分类号】：R96

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