Steady-state kinetics of valproic acid in epileptic patients.

Pharmacokinetic evaluation and prediction were carried out in 20 epileptic patients. Using conventional pharmacokinetic techniques and a one-compartment model, predicted and observed valproic acid plasma concentrations were compared. Valproic acid assay was performed by gas-liquid chromatography. There was good agreement between predicted and observed plasma concentrations. Most patients had predicted half-lives (t1/2s) of 6 to 8 hr, independent of the plasma concentration of valproic acid. Five patients had predicted t1/2s of 12 hr. The correlation between dose and plasma level was poor. Most patients had valproic acid plasma levels between 55 and 100 microgram/ml. Administration of valproic acid three times a day with determination of individual plasma concentrations offers a reliable method of monitoring. Constant levels are maintained in individual patients, but there is substantial intersubject variation.