氯氮平胃内漂浮片兔体内药物动力学和体内外相关性

为了比较氯氮平漂浮片 (自制 )和普通片兔体内药物动力学、相对生物利用度及体内外相关性。用 4只新西兰大白兔自身交叉对照、单剂量灌胃氯氮平漂浮片或普通片各 5 0mg ,采用HPLC法测定血浆氯氮平浓度 ,3p97程序拟合血药浓度 时间数据。结果表明氯氮平漂浮片和普通片符合单室模型特征 ,求得药物动力学参数 :tmax分别为 (3 0 5 7± 0 0 5 9)和 (1 188± 0 191)h ;Cmax分别为 (8 795± 0 494)和 (11 182± 3 45 7) μg/mL ;AUC( 0～t) 分别为 (6 6 0 15± 7 0 2 6 )和 (5 4 881±1 180 ) μg/mL·h ;漂浮片相对生物利用度为 (12 0 2 88± 6 2 77) % ;其体内吸收与体外释药有良好的相关性 (r =0 9811)。

Pharmacokinetics and thecorrelation between in vitro release and in vivo absorption characteristics of clozapinefloating sustained-release tablet in rabbits

To compare the pharmacokinetics and correlation between in vitrorelease and in vivo absorption characteristics between the clozapine floating sustained-release tablets(SRT)and conventional tablets(CT).Four New Zealand rabbits were given orally SRT and CT,with a single dose of 50mg clozapine in self-crossover study.The plasma concentration of clozapine was assayed by HPLC and the pharmacokinetic parameters were calculated with 3p97 program by a computer.Concentration-time curves of SRT and CT fitted to one-compartment open model，respectively.The tmax were（3.057±0.059）and(1.188±0.191）h；Cmax were（8.795±0.494)and（11.182±3.457)μg/mL；AUC(0～t) were（66.015±7.026）and（54.881±1.180）μg/mL.h；the relative bioavailability of SRT was（120.288±6.277）%.It was relatively good in relationship between bioavailability in vivo and dissolution in vitro（r=0.981 1）.The results suggested that SRT has a higher bioavailability than CT.