Pharmacokinetics of sodium valproate in dog and mouse

The pharmacokinetics of sodium di-n-propyl-acetate (sodium valproate, Ergenyl) after i.v. and oral administration in dogs and mice were studied. After i.v. administration of 20 and 40 mg/kg sodium valproate in dogs a biphasic exponential decay of valproate serum concentrations was found, so that a two-compartment open model could be assumed. With mice a monophasic exponential decay of valproate serum concentrations was found after i.v. administration of 200 and 420 mg/kg sodium valproate corresponding to a one-compartment open model. Valproate was rapidly eliminated in both species, the half-life being 90--120 min in dogs (T0.5 beta) and 50 min in mice. After oral administration, valproate was readily absorbed in both species. The transfer of valproate from blood to brains of mice was likewise rapid, and the observed concentrations in brain were 1/4 to 1/5 of that in serum. The binding of valproate to serum proteins determined in dog serum was calculated to 88%. The pKa of valproate was determined to 4.56 and valproate is, therefore, nearly lipid-insoluble at pH 7.4.