Intravenous valproate dosing in neonates

The loading dosage of intravenous valproate required to achieve a desired serum concentration in neonates is not known. Two neonates with seizures received loading doses of intravenous valproate over 30 minutes. Serum valproate concentrations were measured 45 minutes and 3 hours after initiation of the infusion. Both neonates had received phenobarbital and phenytoin before the loading infusions. In the first patient, a loading dose of intravenous valproate of 10 mg/kg increased the 45-minute postinfusion serum valproate concentration to 41 μg/mL with a 3-hour postinfusion serum valproate concentration of 33 μg/mL. In the second patient, a loading dose of 25 mg/kg increased the 45-minute postinfusion serum valproic acid concentration to 100 μg/mL with a 3-hour postinfusion serum valproic acid concentration of 78 μg/mL. We found that each 1 mg/kg of intravenous valproate increased the 45-minute and 3-hour postinfusion serum valproic acid concentrations by approximately 4 μg/mL and 3 μg/mL, respectively. We suggest that these figures be used to calculate the desirable loading dose of intravenous valproate in neonates until larger studies are conducted. The volume of distribution and the serum clearance of valproate were approximately 0.245 L/kg and 25 mL/h/kg, respectively.