Influence of the rate of hepatic portal vein infusion on hexobarbital pharmacokinetics in the rat

Pharmacokinetic parameters of hexobarbital were estimated in rats after hepatic portal infusion of a 10-mg dose. Infusion during 10 min resulted in an area under the blood concentration-time curve (AUC) of 556 +/- 83 micrograms.min/ml and a clearance of 83 +/- 13 ml/min.kg, whereas infusion of the same dose during 40 min resulted in values of 272 +/- 36 micrograms.min/ml and 169 +/- 30 ml/min.kg, respectively (mean values +/- SD, n = 3). Infusion during 15 and 20 min provided intermediate values. The decrease of the AUC and the increase of the blood clearance of hexobarbital following decreasing infusion rates clearly indicate nonlinear pharmacokinetics related to the hepatic inflow concentration of hexobarbital.