Clinical pharmacokinetics of phenytoin in the dog: a reevaluation.

The pharmacokinetics of phenytoin, as well as drug plasma concentrations, during continued treatment were studied in the dog. After IV injection of 10 mg/kg, the average elimination half-life was 4.4 hours, which is in good agreement with previous studies. Bioavailability from tablet formulation was rather poor (av 36% compared with that obtained with IV) and showed great variation between dogs. Even with the dosage regimen of 20 mg of drug/kg given TID orally, therapeutic plasma concentrations could only be maintained for the first 2 or 3 days of treatment; these subsequently decreased to ineffective concentrations during the 1st week of treatment. This effect was accompanied by considerable reductions in half-life, indicating that phenytoin is a strong inducer of microsomal drug metabolism in the dog. Phenytoin must be considered as poorly suited for the treatment of canine epilepsy.