[A single daily dose with valproic acid. A pharmacodynamic and clinical study]

A prospective clinical pharmacokinetic study was carried out in 10 adult patients with primary or secondary generalized tonic-clonic seizures on the efficacy of valproic acid (VPA) administered as a single daily dose in comparison with divided doses thrice daily. The observation period covered 28 weeks. Without changing the total daily dosage the once-daily treatment proved to be of at least equal clinical efficacy. The single daily dose was well tolerated without any increase in adverse effects. Following a once-daily evening dose the VPA plasma profiled displayed--as expected--a steep increase during the early evening hours, reaching a maximal value around 2 a.m.; afterwards the plasma levels decrease continuously until the next evening. By comparison, the thrice-daily regimen gave maximal VPA levels at 2 p.m. With respect to the pharmacokinetic parameters, the minimum VPA plasma concentrations proved to be significantly lower, and the fluctuations significantly higher during the once-daily administration period the mean maximum VPA plasma level was higher, but not significantly so. The bioavailability was not affected by the change in dosage regimen. Since once-daily evening administration results in better patient compliance it seems appropriate to initiate VPA therapy with this simplified dosage regimen. For patients with inadequate seizure control on multiple daily doses of VPA it seems feasible--from a theoretical point of view--that the rate of attacks might be reduced after a changeover to a once-daily evening dosage regimen, but this has not yet been proven in clinical practice.