Dose Of Sodium Valproate Research Articles

Electroencephalographic and behavioural effects of sodium valproate in patients with photosensitive epilepsy. A single dose trial.

A single oral dose of Sodium valproate (VPA) given as Epilim (10 mg/kg) inhibited photoconvulsive responses, especially to 15--30 Hz frequency flicker, in seven out of ten patients with photosensitive epilepsy. In addition, in all patients (with an exception of one) the amplitude of the secondary slow negative wave of the visual evoked potentials was reduced 4--5 h after drug administration. However, in five of these patients the normalization of electrocortical reactions to a single flash and flickering light was accompanied by somnolence and fatigue, moderate slowing of EEG background, development of 3 Hz spike-wave activity and (in three patients) augmented response to hyperventilation. In two patients the EEG photoconvulsive discharge was exaggerated by VPA. There VPA effects suggest that photosensitivity and the underlying epileptic condition have overlapping albeit different pathophysiology. The data offer no support for the conclusion that reduced photosensitivity produced by VPA is associated with the therapeutic potency of the drug.

PHARMACOKINETICS OF SODIUM VALPROATE IN EPILEPTIC PATIENTS AFTER AN INTRAVENOUS BOLUS ADMINISTRATION

Four patients were each given a 400-mg dose of sodium valproate (VPA) by intravenous (i.v.) bolus injection. Concentrations of the drug in plasma were measured at intervals, during the 24 h following the dose, by gas liquid chromatography and the data was used to determine the pharmacokinetic parameters of the drug in these patients.

Effect of single doses of sodium valproate on serum phenytoin levels and protein binding in epileptic patients.

Our study underlines the importance of performing protein binding interaction studies in vivo. Predictions from in vitro studies may be misleading because they may not take into account the kinetics of the drug in the whole animal. Probably the most important clinical implication of these findings is that total serum phenytoin levels may fall when sodium valproate is added to therapy and this may lead to an increase in dose under the mistaken belief that the effect of the drug has been reduced. Since it is the bound and not the free drug which is reduced, phenytoin intoxication may result from this misguided action.

Effects of sodium valproate on the serum protein binding of phenytoin, and on liver enzyme activity.

The effect of a single dose of sodium valproate on the serum protein binding of phenytoin was studied in 6 epileptic patients receiving phenytoin maintenance therapy. Phenytoin was significantly displaced by valproic acid, but the free concentration of phenytoin was unchanged because of redistribution to tissues. As a result of this effect, total serum phenytoin concentration was significantly lowered. Induction of metabolism probably does not play a part in this interaction because antipyrine half-lives and urinary D-glucaric acid excretion were not altered by chronic administration of sodium valproate to 8 patients receiving this drug alone.

The Delayed Effect of Sodium Valproate on the Photoconvulsive Response in Man

The acute effect of a single oral dose of sodium valproate on the photoconvulsive response has been studied. In 7 of 9 patients naive to this drug photosensitivity was abolished or reduced. A similar effect was seen in only 2 of 7 already receiving chronic sodium valproate therapy. The effect appeared 1 to 5 hr (mean, 3 hr) after attainment of peak sodium valproate concentration and lasted up to 5 days.