西替伪麻缓释片在中国志愿者体内的药代动力学研究

摘要

Objective To study the pharmacokinetics of Cetirizine/Pseudoephedrine Extended - Release Tabiet in Chinese volunteers. Methods Tweenty - four healthy volunteers were divided into 2 groups to receive orally a single dose of Cetirizine/Pseudoephedrine Extended - Release Tablet 1 or 2 pills respectively. Then 12 volunteers 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 ±22. 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 pseudoephedrine 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, respectively. The main pharmacokinetic parameters of cetirizine and pseudoephedrine after multi - doses were as follows: Cav were (135. 6 ±23. 4) μg/L and (417. 9 ± 126. 0) μg/L; Tmax were (0. 9 ±0. 5)h and (4. 1 ± 1. 7) h; AUss 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, accurate and convenient. There were no accumulations in vivo after multiple oral doses. Pseudoephedrine had extended - release character from the test tablet.%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(1 369.3.4±314.9)μg·h/L和(2 403.0±304.9)μ·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,AUC0-36 h分别为(6 160.7±1 477.4)μg·h/L和(1 2871.4±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 4±126.0)μg/L,达峰时间(Tmax)分别为(0.9 4±0.5)h和(4.1 4±1.7)h,AUCss分别为(1 626.7 4±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 4±0.1和1.2 4±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.