CLINICAL PHARMACOKINETICS OF PHENYTOIN IN THE DOG - A RE-EVALUATION

  • 1 January 1980
    • journal article
    • research article
    • Vol. 41  (10) , 1635-1638
Abstract
The pharmacokinetics of phenytoin and drug plasma concentrations during continued treatment were studied in the dog. After i.v. injection of 10 mg/kg, the average elimination half-life was 4.4 h, which is in good agreement with previous studies. Bioavailability from tablet formulation was rather poor (average 36% compared with that obtained with i.v.) and showed great variation between dogs. Even with the dosage regimen of 20 mg of drug/kg given TID [3 times daily] 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 wk 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.