PHARMACOKINETICS OF MULTIPLE ORAL DOSE DIVALPROEX SODIUM AFTER INTRAVENOUS LOADING DOSE ADMINISTRATION IN HEALTHY-VOLUNTEERS

A randomised study was conducted in healthy male volunteers to assess the pharmacokinetics of valproate after multiple 500mg (every 8 hours) or 250mg (every 6 hours) doses commencing 1 to 3 hours following an i ntravenous 1000mg loading dose administered over 10 minutes. Multiple blood samples were collected throughout the 73- to 75-hour study perio d and plasma valproate concentrations were quantified using a gas chro matographic technique. All 3 regimens produced near steady-state troug h plasma concentrations generally above 50 mg/L throughout the first s tudy day. By the morning of day 2, pseudo-steady-state conditions had been established. Overall, an intravenous 1000mg loading dose of valpr oic acid followed within 3 hours by oral regimens of divalproex sodium 500mg every 8 hours or 250mg every 6 hours appears to be an acceptabl e approach to rapidly achieve therapeutic concentrations with steady-s tate trough plasma concentrations above 50 mg/L.