High intravenous phenytoin dosage requirement in a newborn infant.
A term neonate was being treated with intravenous phenytoin. To maintain a serum level above 10 micrograms per milliliter and abolish seizure activity, it was necessary to carry out repeated serum concentration measurements, administer several loading doses, and administer an unusually large maintenance dose (25 mg per kilogram per day), divided into a short dosing interval (6 hours). Declining serum levels from postnatal days 8 to 13 on a constant dose of 9 mg per kilogram per day suggested that the rate of phenytoin metabolism was gradually increasing; rapid elimination was documented on day 18 by a half-life measurement of 8.8 hours from three samples. The changing pharmacokinetics were attributed to maturation of oxidative metabolism of phenytoin, concurrent phenobarbital administration, or both. The need for additional loading doses and maintenance dose increases must be guided by serum concentration measurements to obtain maximum benefit with minimal risk of toxicity.
D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000188:drug therapy*; D007700:Kinetics; D010672:Phenytoin / Q000008:administration & dosage* / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy*
D010672:Phenytoin