甲磺司特活性代谢物M-1的人体药代动力学

Pharmacokinetics of active metabolite of suplatast tosilate(M-1) in healthy volunteers

目的:研究甲磺司特活性代谢物4-(3-乙氧基-2-羟基丙氧基)-丙烯酰苯胺(M-1)在健康志愿者体内的药代动力学特征。方法:10名健康志愿者男女各半,单次及多次口服甲磺司特颗粒剂后,采用HPLC-MS法测定人血浆中甲磺司特活性代谢物M-1的浓度,计算药代动力学参数。结果:单次口服甲磺司特颗粒剂100 mg后,甲磺司特活性代谢物M-1的血药达峰浓度为(9.84±2.41)ng/mL;达峰时间为(3.0±1.3)h;AUC为(80.58±10.49)ng.h/mL;消除半衰期为(6.5±1.4)h。多次口服甲磺司特颗粒剂后,甲磺司特活性代谢物M-1的血药达峰浓度为(14.08±1.79)ng/mL;达峰时间为(2.5±1.2)h;AUC为(82.20±12.17)ng.h/mL;消除半衰期为(8.3±1.6)h。结论:多次给药后甲磺司特活性代谢物M-1的人体药代动力学参数与单次给药的药代动力学参数基本一致,AUC与tmax均与性别无关。

Aim： To study the phannacokinetics of the active metabolite of suplatast tosilate （M-1） in healthy volunteers after the single or multiple oral administration. Methods： In the single-dose design, the ten volunteers （consisting of 5 males and 5 females） received a single oral administration of 100 mg suplatast tosilate. And in the multiple dose design,volunteers （consisting of 5 males and 5 females） received multiple doses of 100 mg suplatast tosilate three times a day for consecutive 7 days, and on the 8th day received a single dose of 100 mg suplatast tosilate. The plasma concentration of M-1 was detected by HPLC-MS, and its pharmacokinetic parameters were evaluated. Results： After single dosing of 100 mg suplatast tosilate, the phannacokinetic parameters of M-1 in the healthy volunteers were： Cmax（9.84 ± 2.41）ng/mL, tmax（3.0 ±1.3） h, AUC （80.58 ±10.49）ng·h/mL and t1/2（6.5 ± 1.4） h. After the multiple dosing of suplatast tosilate, the phannacokinetic parameters of M-1 were： Cmax（ 14.08 ± 1.79）ng/ mL, tmax（2.5 ± 1.2）h,AUC （82.20± 12.17）ng·h/mL, and t1/2（8.3 ± 1.6）h. Conclusion：There is no significant difference in the pharmacokinetic parameters of M-1 between single dosing and multiple dosing, and there are no differences in AUC and tmax between female and male volunteers.