Steady-state valproate pharmacokinetics during long term therapy.

As part of a comparative bioavailability investigation, the steady-state pharmacokinetics of the anticonvulsant valproate (given as the sodium salt and the free acid) were studied in 8 epileptic patients who had received long term therapy with the drug. Mean elimination half-life was 8.21 +/- 3.13 hours, mean apparent volume of distribution 0.1868 +/- 0.0641 L/kg and mean plasma clearance 0.0177 +/- 0.0099 L/kg/hour. The magnitudes of these parameters are similar to those reported for single dose studies in patients at the start of valproate therapy. Thus, long term therapy with valproate does not appear to be associated with significant alterations in the human body's disposition of the drug, unlike the situation with certain other anticonvulsants, e.g. carbamazepine.