富马酸卢帕他定片多次给药的药动学研究  

Pharmacokinetics of Multiple Dosing of Rupatadine Fumarate Tablets

作　　者：邹敏[1] 温预关[1] 马斌 梁炯河[1] 

机构地区：[1]广州市精神病医院药剂科/国家药品临床研究基地,广州市510370 [2]中山大学附属第一医院药学部,广州市510080

出　　处：《中国药房》2008年第14期1076-1078,共3页China Pharmacy

摘　　要：目的:研究健康志愿者多次口服国产富马酸卢帕他定片的药动学特点。方法:10例健康受试者(男女各半),每日空腹口服富马酸卢帕他定片10mg,qd,连续7d,应用液-质联用(LC-MS)法测定卢帕他定的血药浓度,采用PKS药动学程序计算卢帕他定药动学参数。结果:卢帕他定在人体内过程符合二室模型,多次给药后的主要药动学参数为Cssmax(3.01±0.91)μg·L-1、tmax(0.78±0.14)h、t1/2Ka(0.32±0.12)h、t1/2α(0.45±0.14)h、t1/2β(6.41±1.69)h、AUC0～t(9.23±3.19)μg·h·L-1、AUC0～∞(9.74±3.17)μg·h·L-1、MRT0～t(5.66±0.67)h、MRT0～∞(7.73±0.81)h、Cssmin(0.05±0.03)μg.L-1、Cssav(0.39±0.13)μg·L-1、DF(783.56±92.88)%。以上参数男女比较均无统计学意义。多次和单次给药所得的药动学参数比较除AUC外均无统计学意义。受试者给药期间未出现明显不良反应。结论:卢帕他定具有快速吸收、快速分布、相对缓慢的消除的药动学特点;多次给药后的药动学过程没有明显改变,仅体内药量有轻微蓄积。OBJECTIVE： To study the pharmacokinetic characters of rupatadine in healthy Chinese volunteers after multiple dosing of oral domestic rupatadine fumarate tablets. METHODS： 10 healthy volunteers （5 females and 5 males） were assigned to receive 10 mg rupatadine fumarate tablets every morning on an empty stomach for 7 d. The plasma concentrations were determined by LC - MS method. The pharmacokinetic parameters of rupatadine were calculated by PKS software. RESULTS： The pharmacokinetics of rupatadine were in line with two- compartment model. The main pharmacokinetic parameters of multiple dosing of rupatadine fumarate tablets were as follows： Cmax^ss（3.01 ± 0.91）μg · L^ -1, tmax（0.78± 0.14）h, t1/2ka（, （0.32± 0.12）h,t 1/2α（0.45 ± 0.14）h,t 1/2β（6.41 ± 1.69）h,AUC0-t（9.23 ± 3.19）μg · L^ -1,AUC0-∞（9.74± 3.17）μg · L^ -1 MRT0-t（5.66±0.67） h, MRT0-∞ （7.73±0.81） h, Cmin^ss（0.05±0.03） μg · L^ -1、 Cav^ss（0.39±0.13）μg · L^ -1, DF（783.56± 92.88）%. No statistical difference was noted between males and females for all the above pharmacokinetic parameters. All pharmacokinetic parameters except AUC were not statistically significant between multiple dose study and single - dose study. No adverse effect was observed in volunteers during medication. CONCLUTION： The pharmacokinetic characteristics of rupatadine in healthy volunteers were characterized by rapid absorption and distribution and relatively slow elimination. There was no significant difference in pharmacokinetic characteristics between single dose and multiple dose of rupatadine except slight drug accumulation after multiple dosing.

关 键 词：卢帕他定 液-质联用法 药动学 

分 类 号：R969.1[医药卫生—药理学]