Correlation of serum phenytoin (diphenylhydantoin) with the administration of oral and intravenous phenytoin in dogs

The concentration of serum phenytoin was determined in normal dogs following the administration of phenytoin by either the intravenous or oral route. An intravenous dose of 11 and 33 mg/kg of body weight was given to six dogs and a further dose of 44 mg/kg was given to two dogs. Serial blood samples were taken following the three doses for determination of pharmacokinetic parameters. The mean half-life was 3.35, 3.84 and 4.57 h as the dose was increased. Signs of toxicity occurred immediately following the infusion of phenytoin (emesis, ataxia and seizures). In the first oral studies, serial blood samples were taken for 2 consecutive days following a dose of 11 and 88 mg/kg, t.i.d. The time—concentration profiles of phenytoin varied significantly from one day to the next in the same dog. In the second oral study, blood samples were taken at 3 and 7 h following a dose of 11, 22, 44, 66 and 88 mg/kg, t.i.d. There was a poor correlation between the size of the oral dose and the concentration of serum phenytoin. Due to the short half-life and poor absorption of phenytoin in dogs, it was concluded that the oral administration of phenytoin in dogs produces sub-therapeutic and erratic serum concentrations of phenytoin which makes its efficacy as an anti-convulsant questionable.