【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(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。更多还原

【Abstract】 AIM To assess the relative bioavailability and pharmacokinetic properties of two types(test and reference) of desogestrel/ethinylestradiol tablets in Chinese Han ethnic volunteers. METHODS The study was performed as an open label, randomized, two- period, single dose cross- over bioequivalence study in twenty- two Chinese Han ethnic healthy male subjects. Both test and reference tablets contain desogestrel 0.15 mg and ethinylestradiol 0.02 mg. The two treatments were separated by a washout period of two weeks. The plasma concentration of 3- ketone- desogestrel( 3- K- DG) was determined by HPLC- MS/MS, and the plasma concentration of ethinylestradiol was determined by radioimmunoassay method. The pharmacokinetic parameters and bioequivalence of the two types of desogestrel/ethinylestradiol tablets were calculated by Win Nonlin software.RESULTS Main pharmacokinetic parameters of the test and the reference preparation were as following: tmaxof3- K- DG were( 1.50 ± 0.44) and( 1.75 ± 0.36) h, cmaxwere( 1.22 ± 0.44) and( 1.15 ± 0.42) μg·L-1,AUC0-twere(27.19 ± 12.13) and(26.13 ± 10.72) μg·h·L-1, t1/2were( 58.61 ± 100.92) and( 60.42 ±37.36) h; tmaxof ethinylestradiol were(2.00 ± 0.41) and(2.00 ± 0.37) h, cmaxwere(147.73 ± 18.66) and(147.77 ± 18.34) ng·L-1, AUC0-twere(1 999.97 ± 1 113.47) and(1 899.12 ± 909.95) ng·h·L-1, t1/2were( 19.47 ± 12.19) and( 19.22 ± 9.34) h, respectively. There was no significant difference in pharmacokinetic parameters between the test and the reference preparation(P > 0.05). The relative bioavailabilities of 3- K- DG and EE of the test preparation were( 104.07 ± 32.78) % and( 105.31 ± 45.31) %( n = 22), respectively.CONCLUSION The established HPLC- MS/MS method and radioimmunoassay method were accurate and sensitive, and the test and the reference of desogestrel/ethinylestradiol tables had bioequivalence.更多还原