多剂量口服盐酸川丁特罗片在健康人体的耐受性和药代动力学  

Tolerability and pharmacokinetics of tratinteroi hydrochloride tablets in healthy subjects after multiple dose administration

作　　者：周颖[1] 赵侠[1] 孙培红[1] 赵东方[1] 张慧琳[1] 程卯生[2] 顾景凯[3] 崔一民[1] 

机构地区：[1]北京大学第一医院药剂科,北京100034 [2]沈阳药科大学制药工程学院,沈阳110016 [3]吉林大学药物代谢研究中心,长春130023

出　　处：《中国临床药理学杂志》2008年第5期407-409,425,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家863计划基金资助项目(2005AA2Z3H40)

摘　　要：目的研究中国健康受试者多剂量口服盐酸川丁特罗片(抗哮喘药)的耐受性、安全性和药代动力学。方法9名受试者第1天和第8天服药1次,第3～7天每天服药2次,每次50μg,观察不良事件,用HPLC-MS/MS测定血浆和尿样中川丁特罗的浓度,用WinNonLin 5.0计算其主要药代动力学参数。结果9名受试者多剂量口服盐酸川丁特罗片后,有1名受试者出现1个与研究药物有关的不良事件,程度均为轻度,未经任何治疗自行恢复,未出现严重不良事件;单剂量和多剂量口服盐酸川丁特罗片50μg后的主要药代动力学参数:C_(max)为(20.2±4.5)、(23.9±6.9)pg·mL^(-1);t_(max)分别为(1.8±1.3)、(1.0±0.5)h;t_(1/2)分别为(17.7±7.1)、(16.9±4.3)h;AUC_(0-tn)分别为(119.9±60.0)、(123.5±49.6)pg·h·mL^(-1)。结论中国健康受试者多剂量口服盐酸川丁特罗片50μg是安全的、能够耐受的;连续给药未见蓄积。Objective To study the tolerability, safety and pharmacokinetics of tratinterol hydrochloride tablets （SPFF） after multiple oral doses of 50 μg in healthy Chinese volunteers. Methods Nine healthy volunteers were randomized to administer a single dose of tratinterol hydrochloride tablets at 50 μg on day 1 and and day 8 and to administer 50 μg twice a day from day 3 to day 7. Adverse event was nearly observed. The concentration of tratinterol hydrochloride in human plasma were determined by HPLC - MS/MS. The main pharmacokinetic parameters were calculated with WinNonLin 5. O. Results Nine healthy volunteers have used SPFF tablets, one adverse event were judged by the investigator to be related to tratinterol hydrochloride tablets, which were mild in severity and abated without any treatment. There were no serious adverse events in this trial. The main pharmacokinetic parameters of tratinterol hydrochloride after single oral doses （50 μg） and multiple dose were as follows： Cmax were （20.2 ± 4.5）, （23.9 ± 6.9） pg·mL^-1; tmax were （1.8 ± 1.3） , （1.0± 0.5） h; t1/2 were （17.7 ±7.1） , （16.9 ± 4.3） h; AUC0-tn were （119.9±60.0）, （123.5 ± 49.6） pg· h · mL^-1, respectively. Conclusion A multiple doses of 50 μg tratinterol hydrochloride tablets were safe and well tolerated in Chinese healthy subjects. There is not cumulation of tratinterol in plasma after multiple dose of 50 μg.

关 键 词：盐酸川丁特罗片 多剂量 耐受性 药代动力学 

分 类 号：R969.1[医药卫生—药理学] R974.3[医药卫生—药学]