Interaction of phenytoin with chloramphenicol or pentobarbital in the dog

Two dogs that had been given phenytoin for control of seizures for approximately 1 year developed signs of phenytoin toxicosis (postural ataxia an d a hypermetric gait) when chloramphenicol was added to the therapeutic regimen. The signs of toxicosis disappeared within 24 hours after cessation of chloramphenicol treatment. Oral treatment of laboratory dogs with chloramphenicol (50 mg/kg, TID for 3 days) prior to intravenous injection of phenytoin increased the half-life of phenytoin from 3 hours to 15 hours. Dogs infused with phenytoin during pentobarbital anesthesia had little or no change in serum phenytoin concentration during a 2-hour postinfusion observation period, which was unexpected for the intravenous route of administration.