血浆中硫普罗宁的测定及其片剂人体生物等效性研究

 目的研究硫普罗宁片在健康人体内的相对生物利用度。方法采用高效液相色谱-质谱法(HPLC-MS)测定了18名健康男性受试者交叉po 200mg的硫普罗宁参比制剂和受试制剂后不同时间血浆中硫普罗宁的浓度,求出主要药动学参数,并进行方差分析和双单侧t检验。结果HPLC-MS测定血浆中硫普罗宁的线性范围为0.02～5mg·L^-1,定量下限为0.02mg·L^-1。日内、日间精密度(RSD)均小于13%,相对回收率介于96%～106%之间。硫普罗宁片参比制剂和受试制剂主要药动学参数:ρ_max分别为(3.54±0.75)和(3.27±1.03)mg·L^-1;t_max分别为(4.6±1.1)和(4.3±1.0)h;AUC_0-96h分别为(18.2±4.5)和(17.6±5.9)mg·h·L^-1;AUC_0-∞分别为(20.4±5.5)和(19.9±6.9)mg·h·L^-1;t_1/2分别为(39.4±14.3)和(41.8±16.5)h。t_max经非参数秩和检验,受试制剂与参比制剂无统计学显著性差异;ρ_max、AUC_0-96h、AUC_0-∞经对数转换后进行方差分析,受试制剂与参比制剂无统计学显著性差异,双向单侧t检验结果表明,受试制剂ρ_max的90%可信限落在参比制剂70%～143%之间,受试制剂AUC的90%可信限落在参比制剂80%～125%之间;以AUC_0-96h计算,受试制剂硫普罗宁片的相对生物利用度为(95.7±26.1)%。结论两种硫普罗宁片制剂具有生物等效性。

Determination of Tiopronin in Human Plasma and Study on Its Bioequivalence

OBJECTIVE To study the pharmacokinetics and bioequivalence of tiopronin tablets in healthy volunteers.METHODS In a randomized crossover study,18 healthy male volunteers were given a single oral dose of 200 mg test and reference tablets.Tiopronin in plasma was determined by a LC-MS method.RESULTS The main pharmacokinetic parameters for tiopronin of reference and test preparations in plasma were as follows:ρ_max were(3.54±0.75) and(3.27±1.03) mg·L^-1;t_max were(4.6±1.1) and(4.3±1.0) h;AUC_{0-96 h} were(18.2±4.5) and(17.6±5.9) mg·h·L^-1;AUC_0-∞ were(20.4±5.5) and(19.9 ± 6.9) mg·h·L^-1;t_1/2 were(39.4±14.3) and(41.8±16.5) h,respectively.The relative bioavailability of tiopronin was(95.7±26.1)%.CONCLUSION The test and reference preparations were bioequivalent.