奥洛他定在健康人体的药动学研究

奥洛他定在健康人体的药动学研究 　    【摘要】  目的建立快速、灵敏的奥洛他定在人体内血药浓度的测定方法，并研究10名健康志愿者单剂量口服5 mg盐酸奥洛他定片后的药动学特点。方法　分别于给药前及口服给药后0.25、0.5、0.75，1、1.5，2、3、4、6、8、10、12、16、24、48 h采集肘静脉血，用高效液相色谱-质谱法测定血浆药物浓度，并采用DAS程序计算主要的药动学参数。结果　单剂量口服盐酸奥洛他定片5 mg后，其血药质量浓度—时间曲线拟合符合二室模型，主要药动学参数分别为：T1/2 (6.55±2.50)h、Tmax(0.98±0.32)h、Cmax(53.75±19?76)μg·L-1、AUC0-48(159.54±60.94)μg·h·L-1、AUC0-∞(161.79±61.19) μg·h·L-1。结论　建立的奥洛他定人体内血药浓度测定方法灵敏、可靠、简便;国产盐酸奥洛他定片单剂量给药后在健康人体内耐受良好。 　    【关键词】  盐酸奥洛他定片;高效液相色谱-质谱法;阿米替林;药动学 　    Abstract:Objective To develop a rapid and sensitive HPLC-MS method for the analysis of olopatadine in human plasma,and study on the pharmacokinetics characteristics of olopatadine hydrochloride tablets after a single oral dose of 5 mg in healthy volunteers.Methods A single oral dose of 5 mg olopatadine hydrochloride tablets was given to 10 healthy volunteers.Blood samples were taken before dosing and at 0.25,0.5,0.75,1,1.5,2,3,4,6,8,10,12,16,24,48 h after a single oral of 5 mg.A HPLC-MS method was used to assay the concentration of olopatadine in plasma.The pharmacokinetic parameters were evaluated with DAS program.Results The concentrations of olopatadine in plasma were fitted with a two-compartment model.The main pharmacokinetic parameters by oral adminstration were as follow: T1/2(6.55±2.50)h，Tmax(0.98±0.32)h，Cmax (53.75±19.76)μg·L-1，AUC0-48(159.54±60.94)μg·h·L-1，AUC0-∞(161.71±61.19) μg·h·L-1. Conclusion The analytical method appeared to be accurate,sensitive and convenient.Olopatadine tablets can be well tolerated in healthy Chinese volunteers after a single dose. 　　Key words: olopatadine hydrochloride tablet; HPLC-MS/MS; amitriptyline; pharmacokinetics 　　盐酸奥洛他定(olopatadine hydrochloride)是一种高选择性的外周H1受体阻断剂，具有抗组胺和抗变态反应活性，属第二代非镇静性抗组胺药，于2000年12 月在日本被批准用于治疗过敏性鼻炎、慢性荨麻疹、湿疹性皮炎、瘙痒、皮肤瘙痒症、寻常性牛皮癣和多形性渗出性红斑。本文参照文献[1]对北京嘉林药业股份有限公司研制生产的盐酸奥洛他定片进行人体药动学研究，为临床用药提供依据。 　　1材料与方法 　　1.1药品与试剂