Abstracts

Objective: To determine whether fosphenytoin (FPHT) is converted to phenytoin (PHT) in infants of very low birth weight (VLBW). Background: An early report has raised concern about the ability of the neonate to convert FPHT to PHT (Takeoka, J Child Neurol 1998;13:537-540). Methods: Retrospective case review of VLBW infants who had received FPHT. Results: In two very low birth weight infants, we observed that FPHT was adequately converted with varying effects upon seizure control. The first infant was born after 28 weeks gestation; the birth weight was 957 grams. At four days of age he began having clinical seizures. After intermittent seizures continued despite repeated doses of phenobarbital and level of 53.7 ?g/ml, a loading dose of 20 mg/kg phenytoin equivalents (PE) of intravenous FPHT was given. The total PHT levels 1.8 hours and 8 hours after the initial loading dose were 11.8 ?g/ml and 12.8 ?g/ml respectively. Seizures stopped shortly following the FPHT load. By mistake, maintenance FPHT 10 mg PE /kg/dose t.i.d. (instead of 10 mg/kg/day) was started. No untoward effects of the high dosage were observed. The total PHT level 3 hours after the 3rd maintenance dose was 32.3 ?g/ml, and 19.7 hours after the 4th FPHT maintenance dose, the total and free PHT levels were 34.1 and 7.4 ?g/ml respectively. The second infant was born at an estimated 21-week gestation with a birth weight of 350 grams. On day 10, clinical seizures began. These continued intermittently despite a series of phenobarbital doses up to 32 mg/kg over 12 hours and a blood level of 27.6 ?g/ml. Two FPHT doses of 7.5 mg/kg PE were given 30 minutes apart. Free PHT levels 12 and 36 hours after the FPHT doses were 2.7 and 1.6 ?g/ml respectively. Seizures continued despite FPHT, and eventually were controlled with a midazolam drip. Because of limited sampling of these VLBW infants, we could not determine how rapidly FPHT was converted to PHT. Conclusion:The FPHT to PHT conversion occurs in infants of VLBW. We recommend close monitoring of free PHT levels while on maintenance FPHT therapy.