[Pharmacokinetic analysis of enterogastric circulation of diazepam in rabbits]

The concentration-time curves of diazepam exhibited double peaks after i.v. 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 provides not only the ordinary pharmacokinetic parameters: T1/2 (alpha) = 0.21 +/- 0.15 h, T1/2 (beta) = 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 microgram.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%.