Valproic acid available forms

Valproic acid (dipropylacetic acid) is a single branched chain carboxylic acid that is structurally unlike any of the other drugs used in the treatment of bipolar disorder or epilepsy. The amide derivative, valproamide, is available in Europe as a more potent form of valproate. Valproate was first developed in Erance as an antiepileptic agent in 1963. As an antiepileptic agent, it was shown to be active against a variety of epilepsies without causing marked sedation. 

For drugs with short half-lives (30 min to 3 h) and a relatively narrow margin of safety, the use of an inconveniently short dosage interval (< 6 h) would be required to maintain plasma concentrations within the therapeutic range. This situation applies to carbamazepine and valproic acid (anticonvulsants), which are commercially available as conventional oral dosage forms. For drugs with a... 

Valproic Acid. Valproic acid (VPA), is available in several chemical forms, including valproic acid, sodium valproate, and divalproex sodium, a stable coordination compound containing equal proportions of valproic acid and sodium valproate. In either of these forms, the dosage is expressed as valproic acid equivalents (Table 6.1) (18).Oral valproic acid derivatives are rapidly absorbed the absolute bioavailability of divalproex extended-release (ER) tablets was about 90% relative to that of the intravenous infusion. The ER form had an average bioavailability of 81 -89%compared to that of divalproex delayed-release tablets given twice daily. The relationship between plasma concentration and clinical response is not clear. This may be attributed to the nonlinear concentration-dependent protein binding of valproic acid, which in turn affects the clearance of the agent (18). 

Pharmacokinetics. Valproic acid appears to be absorbed completely from available oral dosage forms when administered on an empty stomach. However, the rate of absorption differs among preparations. Peak concentrations occur in 0.5 to 1 hour with the syrup, 1 to 3 hours with the capsule, and 2 to 6 hours with the enteric-coated tablet. The extended-release formulation (Depakote-ER) is FDA approved for use in both patients with migraine headache and epilepsy. It should be noted, however, that the bioavailability of this formulation is approximately 15% less than that of enteric-coated divalproex sodium (Depakote). 

---