The decision to start antiepileptic drug therapy with phenobarbital should be evaluated for each individual case and depends on number, frequency, duration and severity of seizures in dogs.
General recommendations for initiating therapy include a single seizure occurring more than once every 4-6 weeks, cluster seizure activity (i.e. more than one seizure within 24 h) or status epilepticus regardless of frequency.
Therapeutic phenobarbital serum concentrations should be monitored to enable the lowest effective dose to be used. Typically, concentrations of 15-40 µg/ml are effective in controlling epilepsy.
Some of the dogs are free of epileptic seizures during the treatment, but some of the dogs show only a seizure reduction, and some of the dogs are considered to be non-responders.
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 individuals and range from about 40-90 hours. Steady state serum concentrations are not reached until 1-2 weeks after treatment is initiated.