Fosphenytoin dosing regimen including optimal timing for the measurement of serum phenytoin concentration in pediatric patients

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Introduction We aimed to evaluate the pediatric fosphenytoin dosing regimen, including optimal timing for the measurement of total serum phenytoin concentration (C PHT ). Methods We retrospectively investigated pediatric patients with status epilepticus or seizure clusters treated with fosphenytoin between April 2013 and March 2018. Two C PHT measurements were analyzed, one 2–4 h after the loading dose and another before the second dose. Individual pharmacokinetic parameters were estimated using the Bayesian method and were used to simulate C PHT . Results The present study involved 12 pediatric patients; the loading dose of fosphenytoin was 22.1 (17.2–27.2) mg/kg. The C PHT was 13.4 (8.6–18.9) μg/mL 2–4 h after the loading dose. The C PHT estimated from individual pharmacokinetic parameters 12 and 24 h after the loading dose was 9.5 (6.7–14.2) and 5.8 (3.7–10.0) μg/mL, respectively. If fosphenytoin was administered at a loading dose of 22.5 mg/kg and a maintenance dose of 5 or 7.5 mg/kg (administered every 12 h, starting 12 h after the loading dose), then the C PHT on day 8 was estimated to be 5.74 (2.6–15.4) μg/mL at 5 mg/kg and 13.9 (5.7–31.0) μg/mL at 7.5 mg/kg. Conclusions In pediatric patients, a maintenance dose of fosphenytoin should be started 12 h after the loading dose, and a maintenance dose of 5–7.5 mg/kg/dose every 12 h may be better than every 24 h. We recommend measuring C PHT at 2 and 12 h after the loading dose to simplify and safely adjust the dosage in clinical practice.