奥昔布宁渗透泵控释片在狗体内单剂量和多剂量药代动力学与生物等.docVIP

奥昔布宁渗透泵控释片在狗体内的单剂量和多剂量药代动力学与生物等效性研究 丁雪鹰1，刘罡一2,余琛2，马建国3，张仰眉1，刘善奎1，高申1* （1.第二军医大学药学院药剂学教研室，上海200433；2.上海市徐汇区中心医院，上海200031；3.北京中惠药业有限公司，北京100085） 摘要: 目的 研究自制奥昔布宁渗透泵控释片与市售普通片以及进口控释片在狗体内的单剂量和多剂量的药代动力学与生物等效性。方法 利用液相-质谱检测血药浓度，采用随机、交叉实验设计对自制控释片、进口控释片和市售普通片进行对照研究。结果 单剂量给药后奥昔布宁自制控释片、进口控释片和市售普通片的峰浓度 (Cmax)、达峰时间 (tmax) 、血药浓度曲线下面积AUC分别为：1.77±0.51ng/ml、1.67±0.27 ng/ml和5.89±2.04ng/ml、10±2.14h、10.50±2.07 h和0.84±0.23h、50.69±11.83ng(h/ml、48.63±6.33 ng(h/ml和22.74±7.06ng(h/ml。多剂量给药后分别为：2.39±0.55ng/ml、2.07±0.41 ng/ml和 7.80±1.56ng/ml、6.12±1.55h、8.12±1.88 h和0.62±0.19h、44.92±10.63ng(h/ml、41.50±9.05 ng(h/ml和21.92±4.37ng(h/ml，达稳态时血药浓度波动系数DF分别为0.76±0.17、0.52±0.17和2.55±0.39。结论 经方差分析和双单侧t检验，自制片与进口片和普通片生物等效。 关键词: 奥昔布宁；渗透泵片；药代动力学；生物等效性；狗 SYUDY ON THE PHARMACOKINETICS AND BIOEQUIVALENCE OF OXYBUTYNIN IN 8 DOGS AFTER A SINGLE AND MULTIPLE ORAL ADMINISTRATION OF OSMOTIC PUMP TABLETS Ding Xue-ying1,Gao Shen1,Liu Gang-yi2,YU Chen2,MA Jian-guo3,ZHANG Yang-mei1,LIU Shan-kui1 (1.Department of Pharmaceutics,School of Pharmacy,Second Military Medical University,Shanghai 200433,China;2.Xuhui Central Hospotial, Shanghai 200031,China;Zhonghui Pharmaceutical Limited Company,Beijing,100085,China) 作者简介：丁雪鹰,女，博士, E-mail：dingxueying@126.com *通讯作者：高申，男，教授，博士生导师Tel：（021Fax：（021ABSTRACT:AIM To study the pharmacokinetics and bioequivalence of self-prepared osmotic pump tablets(OPT) 、imported OPT and immediate-release（IR） tablets of oxybutynin in dogs.METHODS LC-MS method was developed to detect the plasma drug concentration in 9 dogs. Two one-sided T-test and analysis of variance were performed to evaluate the bioequivalence of the formulations.RESULTS The pharmacokinetic parametersof self-prepared OPT 、imported OPT and IR were listed below:for single-dose study: Cmax were 1.77±0.51ng/ml、1.7±0.27 ng/ml and5.89±2.04ng/ml, tmax were10±2.14h、10.50±2.07 h and 0.84±0.23h, AUC were 5±11.83ng(h/ml、4±6.33 ng(h/ml and 22.74±7.06ng(h/ml respectively; for multiple-dose study：Cmax were 2.±0.55ng/ml、2.±0.41 ng