安定在家兔体内的肠胃循环药代动力学分析

6只家兔iv安定5 mg·kg^-1后,浓度—时间数据呈现双峰形。本文提出肠胃循环动力学模型,用于分析实测数据,得到了一般动力学参数:T_1/2(α)=0.21±=0.15 h,T_1/2(β)=2.2+0.6 h,K_e=1.5±0.6 h^-1,K₁₂=2.0±1.0 h^-1,K₂₁=1.0±0.4 h^-1,V₁=3.1±1.6 L·kg^-1,AUC=1.7±0.5μg·h^-1·ml^-1。此外,还求得有关肠胃循环的参数,即:重吸收滞后时间T′=0.25±0.24h,重吸收速率常数K_A=3.5±1.4 h^-1,重吸收率R_A=24±7%。

PHARMACOKINETIC ANALYSIS OF ENTEROGASTRIC CIRCULATION OF DIAZEPAM IN RABBITS

The concentration-time curves of diazepam exhibited double peaks after iv 5 mg·kg^-1 to 6 rabbits. A pharmacokinetic model taking account of enterogastric circulation was proposed to explain this double-peak phenomenon and showed good agreement with data. This model pro-vides not only the ordinary pharmacokinetic parameters: T_1/2(α)=0.21±0.15 h, T1/2(β)=2.2±0.6 h, Ke=1.5±0.6 h^-1, K₁₂=2.0±1.0 h^-1, K₂₁=1.0±0.4 h^-1, V₁=3.1±1.6 L·kg^-1, AUC=1.7±0.5 μg·h^-1·ml^-1, but also the parameters of enterogastric circulation of diazepam: lag time of reabsorption T'=0.25±0.24 h, reabsorption rate constant Ka=3.5±1.4 h^-1, reabsorption rate Ra=24±7%.