Valproate
Valproate
Valproate (VPA) is the drug of choice for primary generalized epilepsies, and is also approved for the treatment of partial seizures. It was discovered by accident; first synthesized in 1882, its antiepileptic properties were recognized when it was used as a solvent for the experimental screening of new antiepileptic compounds.
The mechanism of the VPA is enhances GABA function, but this effect is observed only at high concentrations. It may increase the synthesis of GABA by stimulating GAD. It also produces selective modulation of voltage-gated sodium currents during sustained, rapid, repetitive neuronal firing.
Indication
Idiopathic generalized epilepsy
Myoclonic epilepsy
Partial seizure
Parenteral form
Adverse drug reaction
Teratogenicity
Weight gain, tremor,
Transient hair loss,
Endocrine and metabolic dysfunctions
Dosage and formula
The dosage is range between 500-2400 mg/d. It can be rapid titration because of it’s well tolerated. In children, the usual dose is 20 mg/kg/d and the maintenance dose is 40 mg/kg. Serum level has poor correlation with clinical effect and has significant daily fluctuations.
The parenteral VPA should be administered as a 60-minute infusion with a rate not exceeding 20 mg/min. It is available in Thailand as 200 mg with a round tablet and 500 mg extended-release tablets (Depakine chrono), and 250 mg/5 mL syrup; and parenteral preparation for IV injection.