The antiepileptic effects of phenobarbital are probably the result of at least two mechanisms: decreased monosynaptic transmission, which presumably results in reduced neuronal excitability and an increase in the motor cortex's threshold for electrical stimulation.

After Oral administration of phenobarbital to dogs, the drug is rapidly absorbed and maximal plasma concentrations are reached within 4-8 hours. Bioavailability is between 86%-96%. About 45% of the plasma concentration is protein bound. Metabolism is by aromatic hydroxylation of the phenyl group in the para position, and about one third of the drug is excreted unchanged in the urine. Elimination half-lives vary considerably between individual and range from about 40-90 hours. Steady state serum concentrations are not reached until 1-2 weeks after treatment is initiated.