洛索洛芬胶囊在健康人体内的药动学和相对生物利用度研究

Study on pharmacokinetics and relative bioavailability of loxoprofen capsule in healthy volunteers

目的：建立测定人血浆中洛索洛芬浓度的LC／MS法，研究洛索洛芬胶囊的人体药动学和相对生物利用度。方法：18名健康志愿者随机交叉口服洛索洛芬受试制剂和参比制剂60mg后，用LC／MS法测定其血药浓度，计算其药动学参数和相对生物利用度。结果：洛索洛芬在0．0255～10．20μg／mL范围内线性关系良好，低、中、高3种浓度（O．10、2．65、7．65μg／mL）的回收率分别为90．9％、97．6％和100．7％（n=5）。日内、日间RSD均〈12％。受试制剂与参比制剂t1／2为：（1．54±0．15）和（1．58±0．17）h；cmax为（5．06±0．99）和（4．64±0．75）μg／mL；tmax为（0．38±0．15）和（0．50±0．17）h；AUC0→8为（7．17±1．20）和（6．94±1．05）btg·h·mL^-1；AUC0→∞为（7．32±1．19）和（7．04±1．05）μg·h·mL^-1。受试制剂的相对生物利用度为（103．84±15．64）％。结论：该方法适用于测定洛索洛芬的血药浓度及进行人体药动学研究。受试制剂与参比制剂生物等效。

Objective： To establish a LC/MS method for determination of the plasma concentration of loxoprofen in human plasma and to study its pharmacokinetics and relative bioavailability. Methods： Eighteen healthy volunteers were given 60 mg test or reference loxoprofen orally in a randomized crossover study. The concentration of loxoprofen in plasma was determined by LC/MS method. The pharmacokinetic parameters were calculated and relative bioavailability was studied. Results： The linear range of loxoprofen was 0. 025 5-10.2 μg/mL. The recovery rates at low, middle and high concentrations （0. 10,2.65,7.65 μg/ mL） were 90.9%, 97.6 % and 100.7%, respectively （n = 5）. Both intra-day and inter-day RSD were less than 12%. The t1/2 of test and reference preparations were （1.54±0. 15） and （1.58±0. 17） h, Cmax were （5.06±0. 99） and （4. 64±0.75）μg/mL, tmax were （0.38±0.15） and （0. 50±0.17） h ; AUC0→8 were （7.17±1.20） and （6. 94±1.05） μg· h· mL^-1 ,AUC0→∞ were （7.32±1.19） and （7.04±1.05） μg· h· mL%-1 , respectively. Relative bioavailability of the test preparation was （103.84±15.64）%. Conclusion： This method can be used to study the pharmacokinetics of loxoprofen in human. The two preparations are bioequivalent.