Pharmacokinetic studies with valproic acid in man.

A specific gaschromatographic assay for the simultaneous determination of valproic acid (dipropylacetate, DPA) and ethosuximide was developed. In 13 epileptic patients only treated with DPA a significant correlation(r = 0.88; p less than 0.01) between the minimal steady state plasma level of DPA and its dose (mg/kg body weight) was found. Plasma protein binding experiments in 3 healthy volunteers revealed a relatively strong binding of approximately 95%. The pharmacokinetics of DPA was evaluated after a single oral solution of 600 mg in 2 healthy subjects. Absorption was rapid with maximum plasma levels of approximately 70 microng/ml within 1--3 h. DPA was eliminated with a half-life of 7.9 and 10 h. Assuming 100% absorption a total plasma clearance of 10--13 ml/min and an apparent distribution volume of 0.13--0.16 l/kg were calculated. The urinary excretion of unchanged DPA is neglegible (1% of dose). It is suggested that the great fluctuations of the plasma concentrations within a dosing interval may be minimized by special galenic formulations.