Oral phenytoin in infancy: dose requirement, absorption, and elimination.

Abstract

Oral phenytoin therapy in infants required unexpectedly high doses of about 18 mg/kg body weight to achieve and to maintain serum concentrations between 8 and 25 micrograms/ml. Plasma half-life determined in 12 infants aged 6 weeks to 12 months ranged between 7.9 to 24.9 hours (mean 12.8 +/- 3.6 hours). Measurement of phenytoin metabolite excretion in urine during steady state revealed that only about 30% of the daily given phenytoin is eliminated through the kidneys. Studying the bioavailability of phenytoin in different age groups (infants, children, and adolescents) before and after ingestion of age-appropriate food showed an age-dependent absorption rate and extent, and an influence of the food upon the absorption pattern could be demonstrated. Mechanisms for this phenomenon of an impaired bioavailability of phenytoin in infancy are discussed.