Unusual Absorption Profile of Phenytoin in a Massive Overdose Case

Abstract

The pharmacokinetics of phenytoin was evaluated in a nonepileptic adult man after the ingestion of an undetermined amount of the drug following an apparent suicide attempt. A serum phenytoin concentration of 45 micrograms/mL was observed on admission 12 hours after ingestion. Phenytoin concentrations steadily increased, reached a maximum of 114 micrograms/mL four days later, then fluctuated at about 100 micrograms/mL for a week, and slowly declined to undetectable levels within the following week. At 96.5 micrograms/mL, the unbound serum concentration was 2.5 times that observed in therapeutic drug concentrations. Computer fitting of the data indicated that the Michaelis-Menten constants, apparent volume of distribution, and renal clearance of phenytoin were consistent with those parameters reported after therapeutic doses. However, phenytoin absorption was best described by parallel first- and zero-order rate processes, with the latter proceeding for as long as two weeks following drug ingestion. This protracted absorption appears to be a result of the presence of a large concretion of phenytoin in the gastrointestinal tract, having a slow disintegration and dissolution attributable to the limited solubility of the drug in the gastrointestinal tract and to the patient's diminished intestinal motility.