APPLICATION OF THE 2-COMPARTMENT OPEN MODEL WITH MICHAELIS-MENTEN ELIMINATION KINETICS TO VALPROIC ACID IN THE BILE-EXTERIORIZED RAT

  • 1 January 1980
    • journal article
    • research article
    • Vol. 27  (3) , 469-484
Abstract
The concentration profile of valproic acid (VPA) in bile-exteriorized rats given an i.v. bolus of 15 mg of the anticonvulsant drug sodium valproate (NaVPA)/kg exhibited a limited distribution phase and 1st-order elimination kinetics (2-compartment open model). At a higher dose of 150 mg NaVPA/kg, the initial elimination was non-linear (capacity-limited). Using an iterative modified Euler integration technique, the results were fitted to a pharmacokinetic model which allows for both 2-compartment redistribution of drug and saturable Michaelis-Menten elimination kinetics. A combined pharmacokinetic model of this type has not been described.