氯氮平缓释片在小猎兔犬体内的药动学特性与生物等效性  

Bioequivalence and pharmacokinetics characteristics of clozapine sustained release tablets in Beagle dogs

作　　者：林梅[1] 张正行[2] 王陈[3] 陈怡[3] 范国荣[3] 安登魁[2] 

机构地区：[1]上海市食品药品检验所,上海201203 [2]中国药科大学药学院,江苏南京210009 [3]中国人民解放军第二军医大学药学院,上海200433

出　　处：《中国新药与临床杂志》2007年第7期500-503,共4页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的:研究氯氮平缓释片在小猎兔犬(Beagle犬)体内的药动学特征及其口服相对生物利用度。方法:6条Beagle犬随机分成2组,采用自身对照交叉实验设计,分别单次口服氯氮平缓释片和普通片各100mg,用RP-HPLC法检测血药浓度。药动学参数用统计矩法计算。结果:氯氮平缓释片和普通片的tmax分别为(7.3±s 1.0)和(3.3±0.8)h;Cmax分别为(986±274)和(1388±346)μg·L^(-1),t_(1/2)分别为(8.1±1.4)和(9.5±1.0)h;AUC_(0-t)分别为(17452±5618)和(14174±3420)μg·h·L^(-1)。以AUC_(0-t)计算,与普通片相比,氯氮平缓释片的相对生物利用度为(120±28)％。2种制剂的主要药动学参数经统计学检验,两者差异有显著意义(P<0.05)。结论:氯氮平缓释片具有一定缓释特性,生物利用度优于普通制剂。AIM： To study the oral relative bioavailability and pharmacokinetics of clozapine sustained release tablets in Beagle dogs. METHODS： The self-crossover design was conducted in 6 Beagle dogs. A single dose of clozapine sustained release tablets 100 mg and clozapine generic tablets 100 mg were taken orally in group A and B, respectively. Plasma clozapine levels were determined by a reversed-phase HPLC method. The pharmacokinetic parameters were analyzed by non-compartmental method. RESULTS： The pharmacokinetic parameters were as follows： tmax, cmax, t1/2 and AUC0-t were （7.3 ± s 1.0） h, （986 ± 274） μg·L^-1, （8.1 ± 1.4） h, （17 452 ± 5 618） μg·L^-1 for clozapine sustained-release tablets and （3.3 ± 0.8） h, （1 388 ± 346） μg·L^-1, （9.5 ± 1.0） h, （14 174 ± 3 420） μg·h·L^-1 for clozapine generic tablets. Compare with clozapine generic tablets, relative bioavailability of clozapine sustained-release tablets was （120 ± 28） % based on AUC0-t. There was significant difference between two preparations （P 〈 0.05） . CONCLUSION： Clozapine sustained-release tablet shows prolonged-action characteristics and its bioavailability is better than clozapine generic tablet.

关 键 词：氯氮平 迟效制剂 色谱法 高压液相 药动学 生物等效性 

分 类 号：R969.1[医药卫生—药理学]