Therapeutic monitoring of valproic acid

Valproic acid, a new type of antiepileptic drug, has developed into one of the drugs of first choice in all types of epilepsy with the exception of infantile spasms and partial seizures. Due to its short biological half-life, a steady-state plasma concentration will be reached rapidly after initiation of therapy. However, no direct relationship between this plasma concentration and the clinical effect can be found. In autoradiography experiments, brain distribution appears to change with time, suggesting a gradual accumulation of the drug or its metabolites in certain brain areas. Two metabolites are detected in monkey and human blood plasma. Valprolactone is also found in brain tissue, but the substance is rapidly eliminated. beta, gamma-Unsaturated valproic acid has the longest half-life and is found in concentrations that can be quantitated by routine gas chromatographic analysis. The therapeutic effect appears to correlate better with dosage per kilogram body weight than with the actual plasma concentrations. Routine monitoring of valproate plasma concentrations in epileptic patients seems to be of limited value.