Actual bioavailability of divalproex sodium extended-release tablets and its clinical implications

• Autor(a) principal: Fagiolino,Pietro
• Data de Publicação: 2007
• Outros Autores: Martín,Omar, González,Nicolás, Malanga,Antonio
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Journal of epilepsy and clinical neurophysiology (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1676-26492007000200007
• topic: divalproex sodium; extended-release formulations; bioavailability

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.