Effects of long-term phenobarbital treatment on the liver in dogs

Long-term administration of phenobarbital has been reported to cause hepati c injury in dogs. Phenobarbital induces hepatic enzymes, and it may be diff icult to distinguish the effect of enzyme induction on serum liver enzyme a ctivities from actual hepatic damage. The hepatotoxicity of phenobarbital a nd the impact of enzyme induction on serum liver enzyme activity were inves tigated 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 q12 h, resulting in therapeutic serum phenobarbital concentrations (20-40 mu g/ mL). Serum alkaline phosphatase (ALP), alanine transaminase (ALT), aspartat e transaminase (AST), gamma-glutamyltransferase (GGT), fasted bile acids (f BA), total bilirubin. and albumin were determined before and during treatme nt. Lateral abdominal radiographs, abdominal ultrasounds, and histopatholog ic examinations of liver tissue obtained by ultrasound-guided biopsy were p erformed before and during treatment. Radiographs revealed a moderate incre ase in liver size in most dogs. Ultrasonographic examination revealed no ch ange in liver echogenicity or architecture. No evidence of morphologic live r damage was observed histopathologically. ALP and ALT increased significan tly (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 re flect enzyme induction rather than hepatic injury during phenobarbital trea tment in dogs. Serum AST, fBA, and bilirubin, and ultrasonographic evaluati on of the liver are not affected by the enzyme-inducing effect of phenobarb ital and can therefore be helpful to assess liver disease in dogs treated w ith the drug.