Doses of intravenous valproic acid in a neonate

The dose of intravenous valproic acid required to achieve a desired serum concentration in neonates has not been established. We report the serum valproic acid concentrations reached 3 hours after intravenous valproic acid infusions on four different occasions in a neonate with Otahara syndrome. The patient was on a maintenance dose of valproic acid of 10 mg/kg per day in three divided doses by nasogastric tube. The serum valproic acid concentrations increased 35, 46, 66, and 49 μg/mL (242.5, 318.8, 457.4, 339.6 μmol/L), 3 hours after a dose of 10, 15, 20, and 10 mg/kg, respectively. During the first and second trials 10 mg of valproic acid by nasogastric tube were given prior to the intravenous doses. During the fourth trial 45 mg of valproic acid by nasogastric tube was given 45 minutes after the intravenous dose. This trial was excluded from the calculations. No valproic acid by nasogastric tube was given during the third trial. We conclude that in this patient, each 1 mg of intravenous valproic acid increased the 3-hour post-infusion serum valproic acid concentration by 3.3 ± 0.2 μg/mL. We propose that this ratio be used to calculate the valproic acid dose in neonates until further clinical trials are conducted.