Phenobarbital enhances GABA activity (by binding to a barbiturate receptor on chloride channel complex). This results in higher intracellular concentrations of chloride and hyperpolarisation of the resting membrane potential (increasing the threshold for seizure discharge). The initial elimination half-life of phenobarbital after oral administration is 37 to 89 hours in dogs. However this is significantly decreased with time as a result of increased total body clearance. It takes 12 to 15 days to reach steady state concentration of phenobarbital in dogs. Phenobarbital is primarily metabolised in the liver and causes induction of liver enzymes.


Drug of first choice in management of canine epilepsy.



In dogs, phenobarbital can be started at 3 mg/kg twice daily orally. Oral doses are adjusted based on serum levels and seizure frequency. Recommended therapeutic range in dogs is 20 to 35 ug/ml.


Side effects

Common side effects include polyuria, polydipsia, polyphagia, transient sedation or hyperexcitability and ataxia. These are common one to two weeks after the onset of the treatment or after increasing the oral dosage but usually resolve as tolerance develops. Polyuria, polyphagia and polydipsia are the most common long-term side effects. Other side effects include haematological abnormalities such as neutropenia, anaemia and thrombocytopenia.


Hepatotoxicity is rare (mostly seen in dogs on chronic treatment with phenobarbital serum level above 35 mg/L) and is characterised by sedation, ataxia, anorexia, icterus, ascites or coagulopathy with increased pre- and post-prandial serum bile acids, low albumin, increased ALT, ALP, bilirubin. An increase in liver enzyme concentration is to be expected in all animals receiving phenobarbital and so liver function tests are required to monitor the effects on the liver. Hepatotoxicity may be reversible if detected early and phenobarbital withdrawn. There is an increased risk of pancreatitis in dogs receiving both bromide and phenobarbital.


•  Phenobarbital treatment does not affect adrenal function tests (ACTH stimulation test and low dose dexamethasone test) despite acceleration in dexamethasone metabolism.

•  Phenobarbital treatment significantly decreases total T4 and free T4 concentration. TSH only shows a compensatory increase while total T3 has minimal fluctuation and cholesterol increases toward the upper limits of the normal range.


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Dayrell-Hart B, Steinberg SA, Van winkle et al (1991) Hepatotoxicity of phenobarbital in dogs: 18 cases (1985-1989). JAVMA 199, 1060-1066. - PubMed -


Dyer KR, Shell LG (1993) Anticonvulsant therapy: a practical guide to medical management of epilepsy in pets. Vet Med 88, 647-653.


Gieger TL, Hosgood G, Taboada J et al (2000) Thyroid function and serum hepatic enzyme activity in dogs after phenobarbital administration. JVIM 14, 277-281. - PubMed -


Monteiro R, Anderson TJ, Innocent G, Evans NP, Penderis J (2009) Variations in serum concentration of phenobarbitone in dogs receiving regular twice daily doses in relation to the times of administration. Vet Rec. 165(19):556-8. - PubMed -




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