Phenytoin metabolism in infants following intravenous and oral administration

Developmental Pharmacology and Therapeutics
R D LeffR J Roberts

Abstract

The disposition of phenytoin was examined in 7 infants with a mean age of 22 days and a mean weight of 3,756 g. Multiple doses of phenytoin were administered intravenously and/or orally as a part of required medical care. Gas chromatography/mass spectrometry was employed for analyses of phenytoin and three metabolites - 5-(4-hydroxyphenyl)-5-phenylhydantoin, methylated 3,4-catechol, and 3,4-dihydrodiol - in blood, urine, and feces. Data from identical studies previously conducted in adults were utilized for comparison with the infants. The mean phenytoin dose (+/- SD) in infants was 8.1 +/- 4.4 mg/kg/day, and the mean serum concentration (+/- SD) was 4.8 +/- 4.6 micrograms/ml. In adults, the mean dose was 5.3 +/- 0.6 mg/kg/day, and the mean serum concentration was 12.0 +/- 1.9 micrograms/ml. No significant differences were found between infants and adults in the pattern of urinary metabolites or in the total recovery of phenytoin and metabolites in 24-hour urine samples. These results indicate that pathways for phenytoin metabolism are the same in infants and adults. Absorption of an oral dose of phenytoin in infants appeared to be completely based on recoveries of drug and metabolites in urine and on the fact that less than 3%...Continue Reading

Citations

Mar 21, 2002·Paediatric Anaesthesia·Brian J Anderson, George H Meakin
Dec 20, 2002·Clinical Pharmacokinetics·James H FischerPatricia A Fischer
Oct 1, 1994·Journal of Child Neurology·J T Gilman
Mar 29, 2003·Paediatric Drugs·Jamie T GilmanAna E Campo
Jun 20, 2001·Pediatric Clinics of North America·J S Leeder

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