Bioavailability of a slow-release preparation of valproic acid under steady-state conditions

In six healthy volunteers the bioavailability of two valproic acid preparations (enteric coated tablets and slow-release formulation) was measured in a cross-over study during steady state. A comparison of the mean steady-state plasma levels during a dosing interval and the areas under these curves showed no differences in these parameters. The fluctuations in the monitored plasma levels were similar for both preparations. Based on these results the usual thrice-daily dosage regimen with normal tablets can be favorably replaced by a twice-daily regimen with the slow-release form. Pharmacokinetic evaluation of the data indicated a total plasma clearance of 17.3 +/- 3.6 ml/min (mean +/- SD).