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J Neurol Sci. 1997 Mar 20;147(1):89-92.

Single oral loading dose of phenytoin: a pharmacokinetics study.

Author information

1
Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. dratanak@bgsm.edu

Abstract

In order to determine the optimal single oral loading dose of phenytoin in patients with seizures, a two part study of phenytoin pharmacokinetics was conducted. In the first part, 15 mg/kg of phenytoin was given orally as a single dose to 19 normal medical volunteers with informed consent. Serum concentrations of phenytoin reached the therapeutic level (10 micrograms/ml) with an average of 2.62 +/- 1.25 h. The peak concentrations at 7.26 +/- 4.77 h was 11.95 +/- 2.8 micrograms/ml. The oral loading doses, calculated from a model incorporating a first order of absorption and Michaelis-Menten elimination kinetics to yield the target phenytoin serum concentration of 15 micrograms/ml were 18.7 mg/kg in males and 24.8 mg/kg in females. The larger dose for females is probably required due to the higher total apparent volume of distribution in females than in males. In the second part, seven male and seven female patients with seizures with informed consent received these calculated dosage regimens. For these patients, a single oral loading dose of phenytoin rapidly produced therapeutic concentration (10 micrograms/ml) within an average of 2.04 +/- 0.44 h in males and 2.35 +/- 1.6 h in females with minimal side-effects. For males, the peak concentration at 9.71 +/- 5.94 h was 23.89 +/- 5.46 micrograms/ml and that for females was 21.46 +/- 5.08 micrograms/ml at 7.71 +/- 3.73 h, respectively. Oral loading dose of phenytoin is safe, effective and can be considered in patients who need prompt control of seizures within a few hours, particularly in those areas where medical facilities are limited. It may also replace the intravenous route of phenytoin when the intravenous route is contraindicated.

PMID:
9094065
[Indexed for MEDLINE]

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