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Phenytoin, pharmacokinetics, drug safety, drug dosing
Historically, physicians have been reluctant to maintain infants on phenytoin (PHT) following initial stabilization with intravenous loading doses, as therapeutic blood levels are difficult to achieve with conventional oral doses, and there is concern that high doses will result in toxicity.
To determine the oral dose of PHT required to achieve therapeutic blood concentrations, without clinical toxicity, in the first weeks of life.
Eight infants with seizures were treated with phenytoin from 2 weeks to 3 months of age. Total and free phenytoin concentrations, and urine phenytoin metabolite (p-hydroxyphenytoin) were measured every 2 weeks. Parents were asked to note seizure frequency and complete a questionnaire about possible side effects every 2 weeks.
No infants had seizures and no clinical side effects were noted. Doses required to achieve therapeutic serum concentrations ranged from 10-20mg/kg/day, considerably higher than doses required in adults. Free phenytoin levels were 8-13% of total serum concentrations, similar to ratios reported in adults.
To achieve therapeutic serum phenytoin levels in infants, doses of 10-20 mg/kg/day are required. These higher doses can be safely administered without clinical toxicity.
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