西嗪伪麻缓释片多次给药后伪麻黄碱的人体药动学研究

目的:研究健康受试者多次口服国产西嗪伪麻缓释片后伪麻黄碱的药动学特点。方法:10名健康受试者(男女各半),每次空腹口服西嗪伪麻缓释片(含伪麻黄碱120mg)1片,bid,连续6d。应用液-质联用(LC-MS)法测定血浆中伪麻黄碱浓度,所测数据用DASver2.0程序处理,然后进行药动学研究。结果:多次口服西嗪伪麻缓释片后伪麻黄碱主要药动学参数为t1/2(6.06±0.67)h,tmax(3.90±0.99)h,Cmax(272.03±52.56)ng·mL-1,CL(58.70±16.80)L·h-1,Vd(255.30±71.20)L,AUC0～36(3419.70±750.80)ng·h·mL-1,AUC0～∞(3422.20±751.00)ng·h·mL-1,MRT0～36(9.45±0.61)h,MRT0～∞(9.47±0.61)h。多次口服受试制剂3d后,伪麻黄碱血药浓度达稳态,其稳态药动学参数为Cssmax(272.03±52.56)ng·mL-1,Cssmin(104.99±37.15)ng·mL-1,Cssav(198.55±38.95)ng·mL-1,DF(0.86±0.20),AUCss(2382.61±467.44)ng·h·mL-1。以上参数男女比较均无显著性别差异,另多次和单次给药所得药动学参数比较均无统计学意义。受试者服药期间未出现明显不良反应。结论:西嗪伪麻缓释片中伪麻黄碱有明显的缓释效果;多次给药后伪麻黄碱的药动学过程无明显改变,在正常人体内无蓄积。

Pharmacokinetics of Pseudoephedrine in Healthy Volunteers after Multiple Dosing of Cetirizine and Pseu- doephedrine Sustained Release Tablets

OBJECTIVE： To study the pharmacokinetic profiles of Pseudoephedrine in healthy volunteers after multiple dosing of Cetirizine and Pseudoephedrine sustained release tablets. METHODS： 10 healthy volunteers （5 females and 5 males） received one Cetirizine and Pseudoephedrine sustained release tablet （in which 120 mg pseudoephedrine was contained） bid for 6 consecutive days. The plasma concentration of pseudoephedrine was determined by LC - MS method, and the determined data was treated with DAS vet 2.0 program, then a pharmacokinetic study was performed. RESULTS： The main pharma- cokinetic parameters of Pseudoephedrine in healthy volunteers after multiple dosing of Cetirizine and Pseudoephedrine sustained release tablets were as follows： t1/2（6.06±0.67） h; tmax（3.90±0.99） h; Cmax（272.03±52.56） ng·mL^-l; CL（58.70± 16.80） L·h^-1; Vd（255.30±71.20） L; AUC0-36（3 419.70±750.80） ng ·h ·mL^-1; AUC0-∞ （3 422.20±751.00） ng·h · mL^-1; MRT0-36（9.45±0.61） h; MRT0-∞（9.47 ± 0.61） h. The plasma concentration of pseudoephedrine reached a steady state after multiple dosing for 3 days, and the main pharmacokinetic parameters in steady state were as follows： C^ssmax（272.03±52.56） ng·mL^-1;C^ssmax（104.99±37.15） ng·mL^-1; C^ssmax（198.55±38.95） ng·mL^-1; DF（0.86±0.20）; AUC∞（2382.61±467.44） ng·h·mL^-1. There was no sex difference for the above pharmacokinetics parameters, nor were there significant differences between single dosing and multiple dosing. No adverse effect was observed in volunteers during medication. CONCLUSION： Pseudoephedrine in Cetirizine and Pseudoephedrine sustained release tablets assumed sustained release in healthy Chinese volunteers. The pharmacokinetics process of Pseudoephedrine remain stable and it wouldn＇ t accumulate in body after multiple dosing of Cetirizine and Pseudoephedrine sustained release tablets.