Serum concentrations of primidone and its metabolites, phenylethylmalonamide and phenobarbital, in the dog.

The elimination of primidone, phenylethylmalonamide, and phenobarbital (administered IV) was studied in dogs. The elimination half-lives were primidone, 1.85 +/- 0.3 (SEM) hours; phenylethylmalonamide, 7.1 +/- 1.45 hours; and phenobarbital, 40.9 +/- 4.96 hours. Dogs given repeated oral doses of primidone for 14 or 21 days had smaller primidone serum concentrations after each dosing. Dogs given 1.0 g of primidone orally (59.2 decreasing to 50.5 mg/kg of body weight) for 21 days accumulated the phenobarbital metabolite with apparent steady-state concentrations of 10 to 20 micrograms/ml and phenylethylmalonamide in concentrations of 2 to 5 micrograms/ml. Serum primidone concentrations decreased after repeated dosing and were measurable in only 1 dog 24 hours after the 21st dose and peak concentrations of 4 to 7 micrograms/ml were measured at 4 hours after the 22nd dose.