Effects of Long-Term Phenobarbital Treatment on the Liver in Dogs

Abstract

Long-term administration of phenobarbital has been reported to cause hepatic injury in dogs. Phenobarbital induces hepatic enzymes, and it may be difficult to distinguish the effect of enzyme induction on serum liver enzyme activities from actual hepatic damage. The hepatotoxicity of phenobarbital and the impact of enzyme induction on serum liver enzyme activity were investigated prospectively in 12 normal dogs. Phenobarbital was administered for 29 weeks at 5 mg per kilogram of body weight (range, 4.8-6.6 mg/kg) PO q12h, resulting in therapeutic serum phenobarbital concentrations (20-40 microg/mL). Serum alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), fasted bile acids (fBA), total bilirubin, and albumin were determined before and during treatment. Lateral abdominal radiographs, abdominal ultrasounds, and histopathologic examinations of liver tissue obtained by ultrasound-guided biopsy were performed before and during treatment. Radiographs revealed a moderate increase in liver size in most dogs. Ultrasonographic examination revealed no change in liver echogenicity or architecture. No evidence of morphologic liver damage was observed histopathologically. ALP and ALT increased significantly (P < .05), GGT increased transiently, and albumin decreased transiently during the study. There were no significant changes in AST, bilirubin, and fBA. These results suggest that increases in serum ALP, ALT, and GGT may reflect enzyme induction rather than hepatic injury during phenobarbital treatment in dogs. Serum AST, fBA, and bilirubin, and ultrasonographic evaluation of the liver are not affected by the enzyme-inducing effect of phenobarbital and can therefore be helpful to assess liver disease in dogs treated with the drug.

Spontaneous and Drug-Induced Hepatic Pathology of the Laboratory Beagle Dog, the Cynomolgus Macaque and the Marmoset

“…Similarly the dog has also been reported to be less sensitive to the barbiturate than are rodents (McKillop, 1985;Muller et al, 2000) and in general both the nonhuman primate and the dog have been reported to be less responsive to the induction of enzymes by so-called classic inducers of rodent hepatic enzymes. Figure 10 gives some data from the paper by Amacher et al (2001) on the hepatic response of the dog liver to a number of rodent hepatic enzyme inducing chemicals.…”

Topiramate as an add‐on antiepileptic drug in treating refractory canine idiopathic epilepsy

“…Although most dogs suffering from idiopathic epilepsy (IE) respond well to phenobarbital (PB) monotherapy, 20 to 30% respond inadequately even to a combination of conventional antiepileptic drugs (AED) including PB and potassium bromide (KBr) (Farnbach 1984, Schwartz-Porsche et al 1985, Podell & Fenner 1993, Trepanier et al 1998. Increasing the dosages of PB and KBr in order to decrease the seizure frequency may lead to various adverse effects such as polydipsia, polyuria, polyphagia, sedation, ataxia, weight gain and liver toxicity (Schwartz-Porsche et al 1985, Podell & Fenner 1993, Müller et al 2000. Since poor seizure control and unacceptable side effects decrease the quality of life of dogs with IE and recurrent epileptic seizures may predispose to premature death or euthanasia (Chang et al 2006, Berendt et al 2007, novel effective and safe AEDs are needed to treat these pharmacoresistant patients.…”

Drug-induced blood cell dyscrasia associated with phenobarbital administration in a dog

“…In most dogs, these side effects usually are tolerated after 2 to 4 weeks of therapy [10]. No actual hepatocellular damage during PB treatment has been confirmed; however, PB administration can contribute to the induction of serum liver enzyme activities in dogs [2,8]. In addition, PB has infrequently been associated with hematologic adverse drug events (ADEs) in dogs, including reversible neutropenia, thrombocytopenia, and anemia [5,6].…”