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

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。

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

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 100mg 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,Cmxa,t_(1/2)and AUC_(0-1)were(7.3±s1.0)h,(986±274)μg.L~(-1),(8.1±1.4) h,(17452±5618)μg.h.L~(-1)for clozapine sustained-release tablets and(3.3±0.8)h,(1388±346)μg·L~(-1),(9.5±1.0)h,(14174±3420)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 AUC_(0-1).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.