氯氮平缓释胶囊狗体内相对生物利用度和体内外相关性研究

Bioavailability and the in vitro-in vivo correlation of clozapine sustained-release capsules in dogs

目的 :比较氯氮平缓释胶囊和普通片狗体内药物相对生物利用度和体内外相关性。方法 :采用自身交叉对照法对 8只杂种狗单剂量灌胃氯氮平缓释胶囊或普通片各 75mg,采用高效液相色谱法测定血浆氯氮平浓度 ,3p87程序拟合血药浓度—时间数据。结果 :氯氮平缓释胶囊和普通片符合单室模型特征 ,药物动力学参数 :tmax分别为 (7.1 42 9±1 .5 73 6)和 (1 .92 86± 0 .5 3 45 )h ;Cmax分别为 (0 .5 1 1 3± 0 .2 1 3 7)和 (0 .673 9± 0 .1 799) μg/ml;AUC( 0～τ) 分别为 (9.5 1 74± 2 .5 0 0 7)和 (7.93 92±2 .2 991 ) μg/ml·h;缓释胶囊相对生物利用度为 (1 1 9.5 92 2±9.41 70 ) % ;其体内吸收与体外释药有良好的相关性 (r =0 .9798)。结论 :氯氮平缓释胶囊生物利用度优于普通片 。

Objective:To compare the bioavailability and correlation between in vitro release and in vivo characteristics of clozapine sustained release capsules (SRC)and the conventional tablets(CT).Methods:SRC or CT were given orally to dogs ,with a single dose of 75?mg clozapine in a self crossover study.The plasma concentration of clozapine was assayed by HPLC and the pharmacokinetic parameters were calculated with 3p87 program by a computer. Results:Concentration time curves of SRT and CT fitted to one compartment open model.The tmax was (7.142?9± 1.573?6 )h and (1.928?6±0.534?5)h, respectively;The Cmax was (0.511?3±0.213?7)μg/ml and (0.673?9± 0.179?9 )μg/ml;The AUC was (9.517?4±2.500?7)μg/ml·h and (7.939?2±2.299?1)?μg/ml·h;The relative bioavailability of SRC was (119.592?2±9.410?7)%.There was a significant relationship between absorption in vivo and dissolution in vitro(r=0.979?8). Conclusion:SRT has a higher bioavailability than CT.