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

Abstract

INTRODUCTION:

We aimed to evaluate the pediatric fosphenytoin dosing regimen, including optimal timing for the measurement of total serum phenytoin concentration (CPHT).

METHODS:

We retrospectively investigated pediatric patients with status epilepticus or seizure clusters treated with fosphenytoin between April 2013 and March 2018. Two CPHT 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 CPHT.

RESULTS:

The present study involved 12 pediatric patients; the loading dose of fosphenytoin was 22.1 (17.2-27.2) mg/kg. The CPHT was 13.4 (8.6-18.9) μg/mL 2-4 h after the loading dose. The CPHT 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 CPHT 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 CPHT at 2 and 12 h after the loading dose to simplify and safely adjust the dosage in clinical practice.

• Authors: Go Okamoto, Emari Furuya, Kanae Terada, Kumi Yasukawa, Jun-Ichi Takanashi, Emiko Kobayashi
• Journal: Brain & development (Brain Dev) Vol. 44 Issue 10 Pg. 725-731 (Nov 2022) ISSN: 1872-7131 [Electronic] Netherlands
• PMID: 35879140 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Chemical References

• fosphenytoin
• Phenytoin
• Anticonvulsants

Topics

• Humans
• Child
• Phenytoin (therapeutic use)
• Anticonvulsants
• Retrospective Studies
• Bayes Theorem