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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(P>0.05);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。
Objective To evaluate the pharmacokinetics and bioequivalence of testosterone and reference preparations of desogestrel ethinyl estradiol tablets in Chinese Han healthy subjects. METHODS: Twenty-two Chinese Han healthy male subjects were single-center, open-label and randomized crossover study. Each subject was given 1 tablet or 1 reference formulation (each tablet containing desogestrel 0.15 mg and alkyne Estradiol 0.02 mg) for 2 weeks. The 3-keto-desogestrel (3-K-DG) was determined by HPLC-MS / MS with radioimmunoassay Estradiol concentration of blood, WinNonlin software was used to statistically analyze the main pharmacokinetic parameters of 3-K-DG and ethinyl estradiol in the test and reference preparations, and to evaluate the bioequivalence. Results The tmax of 3-K-DG in test and reference preparations were (1.50 ± 0.44) and (1.75 ± 0.36) h, respectively, and the values of cmax were 1.22 ± 0.44 and 1.15 ± 0.42 μg · L -1 , AUC0-t were (27.19 ± 12.13) and (26.13 ± 10.72) μg · h · L-1, respectively, and t1 / 2 was 58.61 ± 100.92 and 60.42 ± 37.36 h, respectively. The tmax of ethinylestradiol in test and reference preparations were (2.00 ± 0.41) and (2.00 ± 0.37) h, respectively, and the values of cmax were (147.73 ± 18.66) and (147.77 ± 18.34) ng · L- (1 999.97 ± 1 113.47) and (1899.12 ± 909.95) ng · h · L-1, respectively, and t1 / 2 were (19.47 ± 12.19) and (19.22 ± 9.34) h respectively. The test and reference preparations The relative bioavailability of 3-K-DG and ethinylestradiol were (104.07 ± 32.78)% and (105.31 ± 45.31)%, respectively (n = 22 ). Conclusion The established HPLC-MS / MS method is accurate and sensitive to radioimmunoassay. The bioequivalence of two preparations of desogestrel ethinyl estradiol tablets is bioequivalent.