Preliminary observations on valproic acid kinetics in patients with epilepsy

A rapid gas chromatographic method for determination of sodium valproic acid (di-n-propylacetate, DPA) is described. A new sample can be injected every third min, and the reproducibility, in terms of the coefficient of variation, is better than 3%. The method has been used to study clinical pharmacokinetics of DPA in patients with epilepsy during long-term treatment. A poor correlation between daily dose (mg/kg) of DPA and steady state serum levels, attained within few days, was observed. A fixed sampling time in the individual patient, preferably before ingestion of the morning dose, is of great importance for DPA due to extended fluctuations of the serum levels during the day. Most patients had DPA serum levels in the order of 50 microng/ml. No constant relationship was found between increase of the dose and the corresponding increase of the serum levels. Interactions of clinical importance was observed between DPA and other antiepileptic drugs, as addition of DPA resulted in elevated serum levels of diphenylhydantoin and phenobarbital. Carbamazepine levels were unaltered. After withdrawal of DPA the half-life was about 14 h in adult patients. DPA levels in CSF were in the order of 10% of the corresponding serum levels.