For use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types which include absence seizures.
Valproic Acid binds to and inhibits GABA transaminase. The drug's anticonvulsant activity may be related to increased brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by inhibiting enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings. Valproic Acid may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels. It is also a histone deacetylase inhibitor.
Oral, mouse: LD<sub>50</sub> = 1098 mg/kg; Oral, rat: LD<sub>50</sub> = 670 mg/kg. Symptoms of overdose may include coma, extreme drowsiness, and heart problems.
Rapid absorption from gastrointestinal tract.
9-16 hours
Valproate is metabolized almost entirely by the liver. Less than 3% of an administered dose is excreted unchanged in urine.
* 11 L/1.73 m2 [total valproate] * 92 L/1.73 m2 [free valproate]
* total valproate cl=0.56 L/hr/1.73 m2 * free valproate cl=4.6 L/hr/1.73 m2 * 4.8 +/- 0.17 L/hr/1.73 m2 [males, unbound clearance] * 4.7+/- 0.07 L/hr/1.73 m2 [females, unbound clearance]