异烟肼缓释胶囊的研制及药动学  

Preparation and release and pharmacokinetics of sustainedrelease isoniazid

作　　者：郭建平[1] 徐辉[1] 

机构地区：[1]中国人民解放军第272医院

出　　处：《中国药学杂志》1998年第2期95-95,共1页Chinese Pharmaceutical Journal

摘　　要：目的：制备异烟肼缓释胶囊，评价人体内药动学、生物利用度及患者体内血药浓度。方法：乙基纤维素为载体，相分离凝聚法制微囊，转篮法测释放特性；紫外光度法测１０名志愿者单剂量ｐｏ４００ｍｇ异烟肼缓释胶囊与普通片后血药浓度，数据经ＭＣＰ８６药动学程序处理。结果：体外释药：普通片Ｔ５０＝０．０３２ｈ；缓释胶囊：Ｔ５０＝１ｈ，释药１０ｈ以上。普通片ｃｍａｘ＝１１．１２μｇ·ｍｌ－１，ｔｍａｘ＝１．４１ｈ，Ｋ：０．２０１ｈ－１；３６ｈ血药浓度：０μｇ·ｍｌ－１。缓释胶囊：ｃｍａｘ＝４．９９μｇ·ｍｌ－１，ｔｍａｘ＝１．８０ｈ，Ｋ＝０．０３ｈ－１，３６ｈ血药浓度：１．６３μｇ·ｍｌ－１。配对与双侧ｔ检验结果表明：两者除ｔｍａｘ无显著性差异外，ｃｍａｘ及消除速率常数（Ｋ）均有显著性差异（Ｐ＜０．０１）。患者体内血药浓度：普通片与缓释胶囊分别为：１．５ｈ时：（８．２４±２．６０）μｇ·ｍｌ－１，（３．６９±０．５１）μｇ·ｍｌ－１；３６ｈ：０μｇ·ｍｌ－１，２．０９μｇ·ｍｌ－１。结论：该缓释胶囊处方合理、工艺简单，适用于工业化生产，可为结核患者临床防治提供一个新剂型。OBJECTIVE: To prepare and study the pharmacokinetics and release bioavailability in olunteers and concentrations in plasma in patients. METHODS: Ethylcellulose was used matrix in phase separationcoacervation for preparation of microencapsulation. The release experiments were performed in a rotating shaker. The isoniazid concentration in plasma was determined by spectrophotometrical method following a single oral dose of sustainedrelease cupsule and ordinary tablet respectively given to 10 volunteers in a open randomized crossover test. MCP86 was used to process main pharmacokinetic parameters. RESULTS: The sustainedrelease of capsule and ordinary teblet in vitro, T50 was 1 h and 0.032 h respectively. The drug in sustainedrelease capsule was sustained release over 10 h. The main parameters in body: ordinary tablets: cmax=11.12 μg·ml-1, tmax=1.41 h, K=0.201 h-1; sustained release capsule: cmax=4.99 μg·ml-1, tmax=1.80 h, K=0.03 h-1. The concentration of blood at 36 h was (0±0)μg·ml-1 and 1.63 μg·ml-1 respectively. Except tmax, there was significant difference between the two fomulations (P<0.01). The concentration of blood in patient at 1.5 h and 36 h. ordinary tablet and sustainedrelease capsule respectively were (8.24±2.60)μg·ml-1, (0±0)μg·ml-1and (3.69±0.86)μg·ml-1, (2.09±0.56)μg·ml-1. CONCLUSION: The sustainedrelease capsule will play an important part in prevention and treatment of tuberculosis as the result of its reasonable formulation and simple technology.

关 键 词：异烟肼 微囊 缓释胶囊 药物动力学 

分 类 号：R978.3[医药卫生—药品] R944.9[医药卫生—药学]