Pharmacology: Sodium valproate is a broad-spectrum antiepileptic agent. Valproate exerts its effects mainly on central nervous system.
Pharmacological studies in animals have demonstrated that Depakine/Chrono has anticonvulsant properties in various models of experimental epilepsy. (Primary generalized and partial seizures.)
In humans, Depakine/Chrono has also demonstrated antiepileptic activity in various types of epilepsy. Its main mechanism of action seems to be related to a reinforcement of the gabanergic pathway.
Pharmacokinetics: Sodium valproate bioavailability is close to 100% following oral or IV administration. The volume of distribution is mainly limited to blood and rapid exchange extracellular liquid. Valproic acid concentration in cerebrospinal fluid is close to free plasma concentration. Depakine is transferred through placenta. When given to breastfeeding mothers, Depakine is excreted in breast milk at very low concentrations (between 1-10% of the total serum concentration).
Steady-state plasma concentration is reached rapidly (3-4 days) following oral administration; with IV form, steady-state plasma concentration may be reached in a few minutes and then maintained with IV infusion.
Valproate is highly bound to plasma protein, is dose-dependent and saturable.
Valproate molecule can be dialysed but only the free form (approximately 10%) is excreted.
Unlike the other antiepileptics, sodium valproate does not increase its own degradation neither that of other agents eg, estroprogestatives. This is due to the absence of enzyme-inducing effect involving cytochrome P-450.
Half-life is approximately 15-17 hrs.
Sodium valproate is mainly excreted in urine following metabolism via glucuro-conjugation and β-oxidation.
Depakine Chrono: Compared with the enteric-coated form, the slow-release form (Depakine Chrono) is characterized, at equivalent doses, by: Disappearance of lag time following administration; extended absorption; similar bioavailability; total and free peak plasma concentrations (Cmax) are lower (decrease in Cmax of approximately 25% but with a relatively stable plateau from 4-14 hrs after administration); as a result of these loped peaks, valproic acid concentrations are more regular and have a more homogenous distribution among nycthemerus: Following twice-daily administration of a same dose, the range of plasma fluctuations is reduced by half; more linear correlation between doses and plasma concentrations (total and free).