噻托溴铵吸入粉雾剂在大鼠体内的药代动力学研究  

Pharmacokinetic study of dry powder inhalation of tiotropium bromide in rats

作　　者：高文超[1] 李军袖 张晴[1] 徐佳秋[1] 邢晗[1] 李宁[1] 陈西敬[1] 赵娣[1] 

机构地区：[1]中国药科大学药物代谢动力学研究中心,南京210009

出　　处：《中国临床药理学杂志》2016年第1期36-38,共3页The Chinese Journal of Clinical Pharmacology

摘　　要：目的考察两种制备方法下的处方和工艺因素对药物在大鼠体内处置过程的影响以便确定优选工艺。方法大鼠经气管吸入两种处方的干粉[相当于主药6 mg·kg^(-1),气流粉碎(JF)和喷雾干燥(SF)]后,于不同时间点,取气管灌洗液和肺组织,以LC-MS/MS测定药物含量,绘制药物浓度-时间曲线。用WinNonlin~6.1软件建立二房室模型后,比较两者在肺部的药代动力学参数。结果 JF处方和SF处方在大鼠肺内主要药代动力学参数如下:Cmax分别为(4551.69±1731),(2403.09±1096)ng·g^(-1);MRT分别为(2.45±23.10),(1.97±17.20)h^(-1);AUC_(0-8h)分别为(9778.55±869),(4769.40±995)ng·h·g^(-1),差异有统计学意义(均P<0.05)。结论气流粉碎法产物在大鼠呼吸系统中有较高保留,为制备噻托溴铵粉雾剂的优选工艺。Objective To demonstrate the better process for the preparation of dry powder inhalation via investigation of the influence of formulation composition and preparing technique on the disposition of tiotropium bromide（ TIO） in rats. Methods Lung samples and broncho-alveolar lavage（ BAL） of pre-anesthetized rats were collected at different time points after intratracheal inhalation of two dry powder inhalation formulation at single dose（ active parmaceutical ingredient content,6mg·kg^（-1）） and the drug concentration was determined by LC-MS/MS.The pharmacokinetic parameters were calculated based on the special two-compartmental model established by Win Nonlin~ 6. 1 pharmacokinetic program and compared by One-way ANOVA and t-test. Results Jet milling（ JF） and spray dry（ SF） formulation indicated respectively that Cmaxwas（ 4551. 69 ± 1731） ng·g^-1and（ 2403. 09 ± 1096） ng·g^-1,which exhibited significant difference between the two group（ P〈0. 05）;MRT was（ 2. 45 ± 23. 1） h^（-1）and（ 1. 97 ± 17. 2） h^（-1）; AUC_（0-8h） was（ 9778. 55 ±869） ng·h·g^（-1）and（ 4769. 40 ± 995） ng·h·g^（-1）,which exhibited significant difference（ P〈0. 05）. Conclusion The JF exhibited a more prolonged retention time,which may appropriate to be industrialized in the manufacture of clinically used products.

关 键 词：噻托溴铵 吸入粉雾剂 肺组织 药代动力学 

分 类 号：R969.1[医药卫生—药理学] R974[医药卫生—药学]