Fifteen dogs with idiopathic
epilepsy were included in a 9-month clinical trial to determine the therapeutic serum concentrations of
primidone and its active metabolites,
phenobarbital and
phenylethylmalonamide. Dogs with a seizure frequency greater than 1/mo or with a record of multiple
seizures greater than 1/day were chosen for the study. Each dog was given
primidone 3 times daily at dosages intended to maximize seizure control and to minimize undesired side effects. Maintenance period blood samples were taken from fasted dogs 7 hours after dosing in the 3rd, 5th, 7th, and 9th months of the trial to determine therapeutic serum concentrations of
primidone and its metabolites. Two blood samples also were taken from all dogs 7 hours after dosing, during an enforced drowsy period, to establish upper limits of desirable serum concentrations of the
drug. Seizure frequencies during the trial were controlled in 13 dogs, 7 of which had no
seizures during the 9-month trial. The mean percentage reduction in seizure frequency from pretrial frequency was 85%. Two dogs appeared refractory to
primidone therapy. Serum
phenobarbital was the best metabolite of
primidone to use to assess therapeutic serum concentrations. The therapeutic
antiepileptic serum concentration of
phenobarbital was found to be between 25 and 40 micrograms/ml of serum. Serum
phenobarbital concentrations greater than 40 micrograms/ml resulted in side effects in most dogs.