Valparin XR 500 Mechanism of Action

Pharmacology: Valproate exerts its effect primarily on the central nervous system. Its anticonvulsant properties are exerted against a wide variety of epilepsies experimental animal models and humans. Its main mechanism of action seems to be related to reinforcement of the gabaergic pathway.
The various pharmacokinetic studies conducted with valproate demonstrate the following points, some of which may have practical consequences on prescription: the blood bioavailability of valproate following oral administration approaches 100%.
The volume distribution is primarily limited to the blood and to rapid-exchange extracellular fluids. Valproate diffuses into the cerebrospinal fluid and brain.
Half-life is approximately 8 to 20 hours and is usually shorter in children.
Significant therapeutic results are achieved with serum concentrations between 40 to 100 mg/L, but there is no definite correlation between serum level and therapeutic response.
The steady state plasma concentration is achieved rapidly (3 to 4 days).
Valproate is extensively bound to proteins. Binding is dose-dependent and saturable.
Valproate is primarily excreted in the urine following glucuronic acid conjugation and beta-oxidation.
Valproate molecule is dialyzable, but hemodialysis only affects the free fraction of valproate in the blood (approximately 10 percent).
Valproate does not induce enzymes involved in cytochrome P450 metabolism; in contrast to most other anti-epileptics, it therefore does not accelerate its own degradation not that of other substances such as oral contraceptives and oral anticoagulants.
In comparison to the enteric form, the slow-release form sodium valproate, is characterized at equal doses by: disappearance of the absorption latency time; prolonged absorption; similar bioavailability; lowering of maximum plasma concentrations (Cmax) of the total and free fractions (Cmax decreased by approximately 25%, but relatively stable in plateau, between the 4th and 14th hour), this flattening of the peaks makes it possible to achieve more even valproic acid concentrations which are more evenly distributed over the 24-hour cycle: Following twice daily administration of the same dose, the amplitude in plasma fluctuations is reduced by half; more linear correlation between the dose and plasma concentration (total and free fractions).