Application of the two-compartment open model with Michaelis-Menten elimination kinetics to valproic acid in the bile-exteriorized rat.
The concentration profile of valproic acid (VPA) in bile-exteriorized rats given an i.v. bolus of 15 mg sodium valproate (NaVPA) per kg has been previously shown to exhibit a limited distribution phase and first-order elimination kinetics (two-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 have been fitted to a pharmacokinetic model which allows for both two-compartment redistribution of drug as well as saturable Michaelis-Menten elimination kinetics. A combined pharmacokinetic model of this type has not been previously described.
D000818:Animals; D001646:Bile / Q000502:physiology*; D003201:Computers; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D008433:Mathematics; D008954:Models, Biological; D051381:Rats; D013997:Time Factors; D014635:Valproic Acid / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*
D014635:Valproic Acid