Steady‐state kinetics of valproic acid in epileptic patients

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Abstract
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 (t½s) of 6 to 8 hr, independent of the plasma concentration of valproic acid. Five patients had predicted t½s of 12 hr. The correlation between dose and plasma level was poor. Most patients had valproic acid plasma levels between 55 and 100 µg/ml. Administration ofvalproic 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.

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