Unusual Absorption Profile of Phenytoin in a Massive Overdose Case

The pharmacokinetics of phenytoin was evaluated in a nonepileptic adult man after the ingestion of an undertermined amount of the drug following an apparent suicide attempt. A serum phenytoin concentration of 45 μg/mL was observed on admission 12 hours after ingestion. Phenytoin concentrations steadily increased, reached a maximum of 114 μg/mL four days later, then fluctuated at about 100 μg/mL for a week, and slowly declined to undetectable levels within the following week. At 96.5 μg/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.