Twice-daily dosing of valproate with divalproex

Equivalent doses of enteric-coated divalproex were substituted for valproic acid in 15 epileptic patients who were on a three- or four-times-a-day dosing schedule. After 2 wk the dosing regimen was changed to twice-daily divalproex dosing, and plasma levels were determined during the 12-hr period after the morning dose. Peak absorption was reached at 4 hr; extended plateaus were noted thereafter. The mean fluctuation between low and high plasma values for the group was 46%, with a decrease of less than 50% of peak levels in 9 of the 15 patients at a sampling time just before the second dose. Breakthrough seizures did not occur as a result of twice-daily dosing.