伊曲康唑分散片/胶囊人体药代动力学及生物等效性研究  

The study of pharmacokinetics and bioequivalence of itraconazole dispersible tablet/capsule in healthy volunteers

作　　者：李惠云[1] 李小利[2] 王本杰[2] 郭瑞臣[2] 

机构地区：[1]威海市文登中心医院,山东威海264400 [2]山东大学齐鲁医院临床药理研究所,济南250012

出　　处：《中国现代应用药学》2006年第S3期898-900,共3页Chinese Journal of Modern Applied Pharmacy

摘　　要：目的研究伊曲康唑分散片/胶囊在健康志愿者的药代动力学,评价两制剂的生物等效性。方法20例健康志愿者随机单剂量交叉口服伊曲康唑分散片或胶囊200mg,按设定时间采集肘静脉血;采用高效液相色谱法,测定伊曲康唑经时血浓度,计算其药代动力学参数,进行双单侧t-检验和(1-2α)置信区间分析,评价两制剂的生物等效性。结果伊曲康唑最低定量限为5ng.mL-1,在5~600ng.mL-1范围内线性关系良好,回收率、日内、日间差符合生物样品分析要求。伊曲康唑试验制剂和参比制剂主要药代动力学参数t1/2为29.0±6.9h和31.9±8.4h,Tmax为4.8±0.4h和4.8±0.4h,Cmax为301.6±117.3 ng.mL-1和316.4±141.3 ng.mL-1,AUC0~120为6088.64±1780.59ng.mL-1.h和6077.71±1744.69 ng.mL-1.h,AUC0-∞为6403.92±1782.97 ng.mL-1.h和6483.91±1713.40ng.mL-1.h。试验制剂伊曲康唑分散片相对生物利用度F为100.53%±9.58%,双单侧t-检验和(1-2α)置信区间分析显示,两制剂为生物等效制剂。结论HPLC方法测定伊曲康唑血浓度,方法简单,准确,灵敏,适于伊曲康唑血药浓度测定及其药代动力学研究;伊曲康唑试验制剂和参比制剂为生物等效制剂。OBJECTIVE To study the pharmacokinetics and bioequivalence of itraconazole test and reference preparations in healthy volunteers.METHODS Plasma was collected at predetermined time points before and after a single dose of 200 mg itraconazole test or reference preparations in a two-way cross-over test.Itraconazole plasma concentrations were determined by HPLC method using DiamonsilC_(18)(5μm,4.6mm×250mm) column and mobile phase of acetonitrile-water(67.5∶32.5,V/V) at flow rate of 1.5mL·min^(-1).The detection was occurred at 263nm. RESULTS The limit of detection for itraconazole was 5ng·mL^(-1),and a good linearity was obtained in the range of 5～600 ng·mL^(-1).The recovery rate,within-day and between-day variances fulfil the requirement of biological sample analysis.The pharmacokinetic parameters of itraconazole test and reference preparation were as follows t_(1/2) 29.0±(6.9)h and 31.9±8.4h,Tmax 4.8 0.4h and 4.8±0.4h,Cmax 301.6±117.3ng·mL^(-1)and 316.4±141.3ng·mL^(-1),AUC_(0～120)(6088.64)±1780.59ng·mL^(-1)·h and 6077.71±1744.69 ng·mL^(-1)·h,AUC_(0-∞)6403.92±1782.97ng·mL^(-1)·h and 6483.91±(1713.40)ng·mL^(-1)·h,respectively.The relative bioavailability of itraconazole dispersible tablet was 100.53%±9.58%.The t-test and(1-2α) confidence interval analysis show that two preparations were bioequivalent.CONCLUSION The HPLC method was simple,accurate and sensitive,can be used for itraconazole concentration determination and its pharmacokinetic studies itraconazole test and reference preparations were bioequivalent.

关 键 词：伊曲康唑 生物等效性 药动学 生物利用度 高效液相色谱法 

分 类 号：R96[医药卫生—药理学]