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%.