Abstract

FAGIOLINO, Pietro; MARTIN, Omar; GONZALEZ, Nicolás  and  MALANGA, Antonio. Actual bioavailability of divalproex sodium extended-release tablets and its clinical implications. J. epilepsy clin. neurophysiol. [online]. 2007, vol.13, n.2, pp. 75-78. ISSN 1676-2649.  http://dx.doi.org/10.1590/S1676-26492007000200007.

Divalproex sodium extended-release dosage form (divalproex-ER) has been promoted as innovative formulation for the treatment of epilepsy and manic disorders, and for migraine headache prevention, with the advantage of being dosing once a day. Due to a significant decreasing in the peak-trough fluctuation of plasma valproic acid levels, in comparison with the twice-daily dosing of conventional delayed-release formulations (divalproex-DR), concentration-dependent side effects would be prevented. However the main constraint for divalproex-ER usage is the need to be administered in a higher daily dose, because of its lower bioavailability, in order to prevent eventual breakthrough seizures when patients are switched from the twice-daily divalproex DR regimen. Taking into account free plasma drug levels, divalproex ER/DR relative bioavailability could be assessed as low as 75% in fasting condition. In order to overcome the need of increase divalproex-ER daily dose, maintenance of the twice-daily regimen is suggested. Divalproex-ER administered every 12 hours not only increases steady state trough concentration to a higher value in comparison with divalproex-DR, avoiding inefficacy of the treatment, but also achieves the safest manner to treat patients with valproic acid because of reaching practically a plateau profile of drug levels.

Keywords : divalproex sodium; extended-release formulations; bioavailability.