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Pharmacological particulars
Pharmacotherapeutic group: antiepileptics/barbiturates and derivatives
ATCvet code: QN03AA02
Pharmacodynamic properties
The antiepileptic effects of phenobarbital are probably the result of at least two mechanisms, being decreased monosynaptic transmission, which presumably results in reduced neuronal excitability and an increase in the motor cortex's threshold for electrical stimulation.
Pharmacokinetic particulars
As a weak acid, phenobarbital is absorbed well from the gastrointestinal tract following oral administration to dogs, although peak plasma concentrations are not achieved until 4-6 hours after administration.
Plasma protein binding of phenobarbital is 45 % and the distribution volume is 0.7 ± 0.15 l/kg. A steady-state serum concentration is achieved 8-15.5 days after treatment is initiated.
Phenobarbital is reasonably fat-soluble and crosses the blood-brain barrier slowly. The barbiturate effect therefore develops slowly, but persists for a long period of time. Due to the moderate fat solubility of phenobarbital, redistribution to adipose tissue occurs slowly. Phenobarbital crosses the placental barrier and enters breast milk.
Phenobarbital is converted in the liver into p-hydroxy-phenobarbital, which, due to a lower antiepileptic effect, no longer makes any significant contribution to the activity of phenobarbital. Barbiturates cause enzyme induction and thereby accelerate their own breakdown.
About 25 % of the administered dose is excreted in the urine in unchanged form (elimination half-life: 37-75 hours) and about 75 % is excreted as p-hydroxy-phenobarbital glucuronide and sulphate derivatives and as p-hydroxy-phenobarbital itself. Following daily administration of 5.5 mg phenobarbital per kg bodyweight for 90 days, a lower elimination half-life is observed (from 88.7 ± 19.6 to 47.5 ± 10.7 hours).
Under alkaline conditions urinary excretion of phenobarbital is accelerated.
There is wide individual variation in the degree of phenobarbital metabolism which is caused by the effect of phenobarbital on microsomal liver enzymes. Variations in elimination half-life are not only seen between animals but also within a single animal.