西替伪麻缓释片在中国志愿者体内的药代动力学研究

Study on Pharmacokinetics of Cetirizine/Pseudoephedrine Extended-Release Tablet in Chinese Volunteers

目的研究中国健康志愿者口服西替伪麻缓释片的药动学过程。方法将24名志愿者随机均分为高剂量组和中剂量组,分别单次口服西替伪麻缓释片1片和2片;单次给药结束1周后,中剂量组12名受试者连续5 d每天口服2片,采用液相色谱-串联质谱法同时测定人血浆中西替利嗪和伪麻黄碱的质量浓度。结果西替利嗪单次给药后高剂量组和中剂量组的血药峰浓度(Cmax)分别为(134.5±22.0)μg/L和(290.9±47.4)μg/L,0～36 h药时曲线下面积(AUC0-36h)分别为(1 369.3±314.9)μg.h/L和(2 403.0±304.9)μg.h/L;伪麻黄碱单次给药后高剂量组和中剂量组的Cmax分别为(434.2±95.0)μg/L和(932.5±280.8)μg/L,AUC0-36h分别为(6 160.7±1 477.4)μg.h/L和(12 871.4±4 863.2)μg.h/L。多次给药达稳态后的平均稳态血药浓度(Cav)分别为(135.6±23.4)μg/L和(417.9±126.0)μg/L,达峰时间(Tmax)分别为(0.9±0.5)h和(4.1±1.7)h,AUCss分别为(1 626.7±280.8)μg.h/L和(5 015.0±1 511.8)μg.h/L,波动度(DF)分别为1.3±0.2和0.7±0.2,蓄积系数(R)分别为1.3±0.1和1.2±0.1。结论所建立的液相色谱-串联质谱法测定方法快速、灵敏、准确、简便;盐酸伪麻黄碱具有缓释特征,多次给药后在体内无蓄积现象。

Objective To study the pharmacokinetics of Cetirizine/Pseudoephedrine Extended-Release Tablet in Chinese volunteers.Methods Tweenty-four healthy vo lunteers were divided into 2 groups to receive orally a single dose of Cetirizin e/Pseudoephedrine Extended-Release Tablet 1 or 2 pills respectively.Then 12 vol unteers of the total each received 2 tablets per day for 5 consecutive days.The concentrations of cetirizine and pseudoephedrine in human plasma were determined simultaneously by LC-MS/MS method.Results The main pharmacokinetic parameters of cetirizine of 2 groups after single-dose were as follows：Cmax were（134.5±2 2.0）μg/L and（290.9±47.4）μg/L;AUC0-36 h were（1 369.3±314.9）μg·h/L and（2 403.0±304.9）μg·h/L,respectively.The main pharmacokinetic parameters of pseu doephedrine were as follows：Cmax were（434.2±95.0）μg/L and（932.5±280.8）μg/L;AUC0-36 h were（6 160.7±1 477.4） and（12 871.4±4 863.2）μg·h/L,respectivel y.The main pharmacokinetic parameters of cetirizine and pseudoephedrine after mu lti-doses were as follows：Cav were（135.6±23.4）μg/L and（417.9±126.0）μg/L;T max were（0.9±0.5）h and（4.1±1.7）h;AUCss were（1 626.7±280.8）μg·h/L and（5 015.0±1511.8）μg·h/L;DF were 1.3±0.2 and 0.7±0.2,R were 1.3±0.1 and 1.2±0.1,respectively.Conclusion The method was proved to be rapid,sensitive,accura te and convenient.There were no accumulations in vivo after multiple oral doses. Pseudoephedrine had extended-release character from the test tablet.