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.
D000328:Adult; D002648:Child; D002675:Child, Preschool; D002849:Chromatography, Gas; D004827:Epilepsy / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D011485:Protein Binding; D014631:Valerates / Q000378:metabolism*; D014635:Valproic Acid / Q000378:metabolism*
D014631:Valerates; D014635:Valproic Acid