Evaluation of the effect of phenobarbital administration on the biochemistry profile, with a focus on serum liver values, in epileptic cats

Abstract

Objectives Phenobarbital (PB) is the most common antiseizure drug (ASD) used for the management of feline epilepsy. In dogs, PB is known to cause serum liver enzyme induction and hepatotoxicity, especially after administration long term or in high concentrations. In cats, insufficient evidence is available to draw similar conclusions. The aim of this study was to evaluate the effect of PB administration on the serum biochemistry profile of epileptic cats. As an additional objective, other adverse effects arising, related to PB treatment, were recorded. Methods Medical records of four veterinary centres were retrospectively reviewed for epileptic cats receiving PB treatment. Cats were included if they had a diagnosis of idiopathic epilepsy or structural epilepsy; a normal baseline serum biochemistry profile; at least one follow-up serum biochemistry profile; no concurrent disease or had not received medication that could possibly influence liver function or lead to serum liver enzyme induction. Alkaline phosphatase, alanine aminotransferase (ALT), aspartate transaminase and gamma-glutamyl transferase activities, and total bilirubin, bile acids, glucose, albumin, total protein, urea and creatinine concentrations before and during PB administration were recorded. PB serum concentration was also recorded, when available. Results Thirty-three cats (24 males, nine females) with a median age of 3 years (range 2 months to 12 years) met the inclusion criteria. Idiopathic or structural epilepsy was diagnosed in 25 (76%) and eight (24%) cats, respectively. The follow-up period ranged from 9 to 62 months. This study found an increase in ALT in three cats, possibly related to a PB serum concentration >30 µg/ml. No statistically significant increase in serum liver enzymes or other evaluated biochemistry parameters was found by comparing pre- and post-treatment parameters. Conclusions and relevance PB administration did not result in hepatic enzyme induction or other biochemical abnormalities in cats. This strengthens the safety profile of PB as an ASD in cats.

Evaluation of antiseizure medications including zonisamide in feline idiopathic epilepsy at a referral hospital in Japan

“…Elevation of liver enzyme activity (not otherwise specified) was observed in two cats, of which one received PB and ZNS and the other received PB and DZP. PB sometimes causes elevated alanine transferase levels in cats ( Finnerty et al , 2014 ; Hermans et al , 2022 ), therefore elevation of liver enzyme observed in this study possibly is explained by the use of PB. ZNS has also been reported to induce elevation of the levels of liver enzymes, especially alkaline phosphatase, in dogs ( Klopmann et al , 2007 ; Boothe and Perkins, 2008 ; Dewey et al , 2014 ; Smith et al , 2022 ) but the exact mechanism of why this elevation of liver enzyme occurs is still undetermined.…”

A retrospective evaluation of phenobarbital‐induced hematologic changes in 69 cats

“…7,8 Furthermore, the effect of PB on the liver is well known, leading to hepatic enzyme induction; however, these changes have not been observed in cats. 9 Compared with a study in PB-treated dogs by Pakozdy et al…”

“…The most common are cytopenia, lymphadenopathy, pseudolymphoma, skin eruptions, pyrexia, and coagulopathy 7,8 . Furthermore, the effect of PB on the liver is well known, leading to hepatic enzyme induction; however, these changes have not been observed in cats 9 …”

Co-Treatment With Cranberry and Vitamin-C Ameliorates the Hepato-Renal Toxicities Induced by Phenobarbital in Wistar Rats

“…Phenobarbital (PB) is the drug of choice for long-term treatment of epilepsy but it exerts some undesirable side effects 5,7 . This study aimed to investigate whether CB or/and Vit-C have ameliorative effects against the hepatorenal toxicity that induced by PB-treatment.…”