Pharmacokinetics of Multiple Oral Dose Divalproex Sodium after Intravenous Loading Dose Administration in Healthy Volunteers

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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 intravenous 1000mg loading dose administered over 10 minutes. Multiple blood samples were collected throughout the 73- to 75-hour study period and plasma valproate concentrations were quantified using a gas chromatographic technique. All 3 regimens produced near steady-state trough plasma concentrations generally above 50 mg/L throughout the first study day. By the morning of day 2, pseudo-steady-state conditions had been established. Overall, an intravenous 1000mg loading dose of valproic acid followed within 3 hours by oral regimens of divalproex sodium 500mg every 8 hours or 250mg every 6 hours appears to be an acceptable approach to rapidly achieve therapeutic concentrations with steady-state trough plasma concentrations above 50 mg/L.

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