Intravenous valproate dosing in neonates

The loading dosage of intravenous valproate required to achieve a desired s erum concentration in neonates is not known. Two neonates with seizures rec eived loading doses of intravenous valproate over 30 minutes. Serum valproa te 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 mug/mL with a 3-hour postin-fusion serum valproate con centration of 33 mug/mL. In the second patient, a loading dose of 25 mg/kg increased the 45-minute postinfusion serum valproic acid concentration to 1 00 mug/mL with a 3-hour postinfusion serum valproic acid concentration of 7 8 mug/mL,. We found that each I mg/kg of intravenous valproate increased th e 45-minute and 3-hour postinfusion serum valproic acid concentrations by a pproximately 4 mug/mL and 3 mug/mL, respectively. We suggest that these fig ures be used to calculate the desirable loading dose of intravenous valproa te in neonates until larger studies are conducted. The volume of distributi on and the serum clearance of valproate were approximately 0.245 L/kg and 2 5 mL/h/kg, respectively.