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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.

Keywords

Epilepsy antiseizure drug phenobarbital hepatotoxicity

Introduction

Recurrent epileptic seizures have an estimated prevalence of 0.16%¹ in the general cat population and 0.5–3.5% in the referral cat population, respectively.^2–5 Recurrent epileptic seizures can occur because of idiopathic epilepsy (IE; suspected genetic epilepsy or epilepsy of unknown cause), structural epilepsy (related to intracranial pathology) or reactive seizures (related to a metabolic or toxic imbalance).⁶ IE appears to be the cause for recurrent epileptic seizures in 21–59% of cats.^3,7 Phenobarbital (PB) is currently the first-choice antiseizure drug (ASD) in cats.^8–10 PB has been shown to be a safe and effective drug in cats, with reported epileptic seizure control of up to 93%¹¹ within a therapeutic serum PB concentration range of 15–30 µg/ml.^12,13 Most adverse effects (AEs) in cats are mild and include sedation, ataxia, polyphagia, polydipsia, polyuria and weight gain.^13–15 Severe AEs, including pseudolymphoma,^16,17 cutaneous eruptions¹⁸ and blood dyscrasias,^5,14,15 are rare and subside after discontinuation of PB therapy.⁸

In dogs, PB is known to cause liver enzyme induction, even within the therapeutic serum concentration, owing to its potent effect on hepatic cytochrome (CY) P450 activity.^19–21 At a clinically effective dose there is an induction of the CYP1A, CYP2B, CYP2C and CYP3A subfamilies.^19,22 In dogs, the effect of liver enzyme induction is mainly seen for alkaline phosphatase (ALP) and alanine aminotransferase (ALT) activities, the two liver enzymes most commonly used as markers for hepatic disease.^{20,21,23–27} Induction of CYP450 significantly increases the hepatic production of oxygen species that are thought to cause hepatic injury at the cellular level.²⁸ A systematic review and meta-analysis reported an increase in serum ALP and ALT, in 60% and 45%, respectively, of the analysed studies, without the presence of hepatotoxicity.²³ However, hepatic injury and severe hepatotoxicity caused by PB treatment have previously been reported in dogs.^23,29,30

With liver disease, other biochemistry parameters can also be affected. Albumin (ALB) and glucose are synthesised by the liver, and a decrease in both parameters is expected in liver disease.³¹ The uptake and excretion of total bilirubin (TBIL) and bile acids (BA) are decreased in liver disease, which leads to an increased serum concentration of both parameters.³¹ Ammonia is converted to urea by the liver. In animals with liver disease, serum urea concentration is decreased.³¹ Changes in some of these parameters have also been reported in dogs under PB treatment.^21,26,32

In cats, there is controversy regarding PB-induced serum liver enzyme induction. The induction of serum liver enzymes in cats is not expected because of the low activity of CYP2C.³³ An increase in ALT and ALP in cats treated with PB has been reported in three studies.^8,15,34 A fourth study reported a transient increase in ALT in one cat treated with PB.¹¹ These studies did not report clinical signs related to hepatic disease and lacked information on further investigations to exclude other underlying causes for the increase in the serum liver enzymes. Two other studies reported no effect on liver enzymes in 15 cats being treated with PB.^35,36 However, no study has evaluated the effect of PB on the liver of cats, in particular a comparison of the activity of liver enzymes and other biochemistry parameters before and during PB treatment. Based on this and the fact that hepatotoxicity can be a severe and potentially lethal AE, our study aimed to (1) report the effect of long-term PB administration on the serum biochemistry profile (particularly serum liver enzymes such as ALT and ALP) of cats; and (2) assess whether PB in cats leads to serum liver enzyme induction as commonly occurs in dogs.

Materials and methods

Case selection

A retrospective review of medical records (1994–2019) of cats with epilepsy, regardless of breed, sex or age, receiving long-term PB was performed in four veterinary centres: the Small Animal Department at the Faculty of Veterinary Medicine (Ghent University, Belgium), the Clinical Unit of Internal Medicine Small Animals at the University of Veterinary Medicine in Vienna (Austria), the Department of Small Animal Medicine and Surgery at the University of Veterinary Medicine in Hannover (Germany) and the Small Animal Clinic AniCura Kalmarsund in Kalmar (Sweden).

Cats with IE and structural epilepsy were included. IE was diagnosed based on the signalment, unremarkable interictal physical and neurological examinations, and exclusion of metabolic, toxic and structural cerebral disorders by means of diagnostic investigations.³⁷ Furthermore, cats were included if: (1) baseline (ie, pre-PB treatment) blood examination, including a serum biochemistry profile, was performed within the 3 months before the start of PB; (2) baseline serum values for ALT, ALP, aspartate transaminase (AST) and/or gamma-glutamyl transferase (GGT) were within the reference intervals (RIs); (3) at least one follow-up blood examination, when the cat had been receiving PB for at least 1 month, was available; (4) cats had no other concurrent disease potentially influencing liver function; and (5) no other medication known to affect liver enzyme activities or liver function (eg, prednisolone, diazepam and ketoconazole) was administered. Adjunctive therapy with levetiracetam (LEV) and imepitoin (IMP) was allowed.

Outcome assessment

In each cat, the baseline (pretreatment) and follow-up (post-treatment) serum biochemistry values were compared. The following variables were evaluated: ALP, ALT, AST, GGT, TBIL, BA, glucose, ALB, total protein, urea and creatinine. PB serum concentration was also recorded, when available. As our study included data from different centres and laboratories, a common RI for each serum biochemistry parameter was used. Precisely, the values were converted into ratios in relationship to the laboratory-specific RI for each parameter. The ratios were calculated by dividing the absolute value of the serum biochemistry variable by the upper limit of the laboratory’s RI. These ratios were compared for each biochemistry parameter pretreatment to the last available post-treatment value. Serum liver enzymes in cats were considered to be increased when the ratio was >1, which means the upper RI was exceeded. If the ratio was >1, further diagnostics were preferably performed to screen for underlying liver disease. PB serum levels were documented, and in a number of cats an increase in serum liver enzyme function seemed to be correlated with a PB concentration >30 µg/ml. The follow-up period (ie, the time between the pretreatment and last available post-treatment bloodwork) was also recorded for each cat. All possible AEs related to PB treatment were recorded in the included cats.

Statistical analysis

Statistical analysis was conducted in R version 3.6.3. All parameters were reported as median and range. A Wilcoxon signed-rank test was used to compare the blood variables at baseline and the last available post-treatment measurement. To correct for multiple testing, a Bonferroni correction was applied by multiplying every P value obtained with 11 (ie, the number of tests). Significance was set at P ⩽0.05.

Results

Signalment and baseline characteristics

Overall, the records of 218 cats with recurrent epileptic seizures were retrieved. Thirty-three cats met the inclusion criteria. A detailed overview of the signalment, disease and treatment characteristics is provided in Table 1. The main reason for exclusion was the lack of availability of follow-up blood sampling and concurrent treatment with medication that possibly affects liver function or liver enzyme activities. Breeds included were European Shorthair (n = 25), British Shorthair (n = 3), Maine Coon (n = 2), Ragdoll (n = 1), Russian Blue (n = 1) and Sphynx (n = 1). The median age at epileptic seizure onset was 3 years (range 2 months to 12 years). Twenty-four cats (72.7%) were male (three intact and 21 neutered) and nine (27.3%) were female (all neutered). Median body weight was 4.95 kg (range 0.9–9.6). Twenty-five cats (75.8%) were diagnosed with IE. In this group of cats 13 (52%) underwent MRI and 12 (48%) had cerebrospinal fluid examination. The remaining eight cats (24.2%) were diagnosed with structural epilepsy based on MRI. Causes included hydrocephalus (n = 1), encephalitis (n = 1), hippocampal sclerosis (n = 3), porencephaly (n = 1) and pachygyria (n = 1). In one cat the structural disease was not further specified (Table 1).

All 33 cats were started on PB monotherapy, except for two cats in which PB and LEV were started simultaneously owing to the high frequency of epileptic seizures (Table 1). The median PB dose at initiation of therapy was 4 mg/kg/day (range 1.5–7.5). In 18 cats, the PB dose was adapted based on monitoring of the PB serum concentration (Table 1). In six cats a second ASD was initiated owing to poor seizure control. LEV was added (n = 4) at a dosage of 20 mg/kg PO q8h within a median of 12 months (range 4–24) after PB initiation. IMP (n = 2) was added at a dosage of 20 mg/kg PO q12h 30 months after the initation of PB in both cats (Table 1). The median follow-up period for cats treated with PB in this study was 11 months (range 1–62).

Table 1

Details of the baseline characteristics, diagnosis, individual treatment protocols and follow-up data of 33 epileptic cats

Cat number	Age at start of PB treatment (months)	Breed	Sex	Diagnosis	First ASD	Second ASD (timepoint in relation to start of PB therapy, months)	Starting dose of PB (mg/kg/day)	PB dose adjustments (mg/kg/day)*	Last measured PB serum concentration (mg/l) (range)	Follow-up period until latest bloodwork (months)
1	84	ESH	FN	IE	PB	–	5	8 (1)	62 (–)	1
2	32	BSH	MI	IE	PB	LEV (23)	4	6 (3) 8 (4) 6 (12) 4.6 (23) 4 (30)	50 (17–50)	31
3	19	Ragdoll	MN	IE	PB	–	3.8	–	24 (16–24)	9
4	84	ESH	FN	IE	PB	–	4.6	–	12 (12–12)	1
5	41	BSH	MN	IE	PB	LEV (9), IMP (30)	5	4.4 (7)	20 (20–44)	39
6	48	Russian Blue	FN	IE	PB	LEV (4)	3.6	6 (4)	30 (20–30)	15
7	80	ESH	MN	IE	PB	–	3.8	–	5 (5–9)	13
8	48	Sphynx	FN	Hippocampal sclerosis	PB	IMP (12)	4.8	7 (4) 6 (12)	25 (18–38)	24
9	12	ESH	MN	IE	PB	–	1.5	5 (22)	27 (21–27)	22
10	60	ESH	FN	IE	PB	–	4	2 (11)	16 (16–35)	45
11	42	ESH	MN	IE	PB	–	2	1.5 (41) 1 (45)	14 (14–23)	45
12	60	ESH	FN	IE	PB	–	5	2.5 (13)	16 (12–16)	47
13	36	ESH	MN	IE	PB	–	4	7 (1) 5 (18)	20 (20–40)	18
14	24	ESH	MN	IE	PB	–	1.8	–	14 (10–14)	7
15	11	ESH	MN	IE	PB	–	4	2.6 (2) 2 (4)	18 (–)	11
16	19	BSH	MN	IE	PB	IMP (8)	4	–	20 (20–38)	14
17	24	Maine Coon	MN	IE	PB	–	2	–	21 (21–32)	5
18	36	ESH	MN	Hippocampal sclerosis	PB	–	5.4	5 (12)	22 (22–24)	7
19	144	ESH	MN	IE	PB	–	5.4	–	7 (5–7)	13
20	24	ESH	MN	IE	PB	–	7.5	–	13 (13–22)	7
21	36	ESH	MN	IE	PB	LEV (24)	5	–	7 (3–7)	12
22	24	ESH	MN	IE	PB	–	2	–	–	56
23	60	ESH	MN	IE	PB	–	2.4	4 (unknown time point)	–	53
24	36	ESH	MN	Hydrocephalus	PB	–	2	–	7 (–)	1
25	10	ESH	MN	Structural (not further specified)	PB	–	2	6.4 (24)	12 (9–12)	62
26	12	ESH	MI	Encephalitis (not further specified)	PB	LEV (0)	4	5 (4)	11 (–)	4
27	142	ESH	FN	IE	PB	–	5.2	–	13 (13–16)	6
28	–	ESH	FN	Pachygyria	PB	–	3.2	–	13 (–)	1
29	127	ESH	MN	IE	PB	–	2.6	–	–	2
30		ESH	MN	IE	PB	–	6	–	28 (–)	3
31	84	Maine Coon	FN	Hippocampal sclerosis	PB	–	5	–	–	1
32	2	ESH	MI	Porencephaly	PB	LEV (0)	6	–	17 (12–17)	5
33	17	ESH	MN	IE	PB	–	5	3.6 (3)	16 (16–20)	4

PB = phenobarbital; ASD = antiseizure drug; ESH = European Shorthair; FN = female neutered; IE = idiopathic epilepsy; BSH = British Shorthair; MI = male intact; LEV = levetiracetam; MN = male neutered; IMP = imepitoin

Time point of adjustment in relation to the start of PB therapy (in months)

Information concerning AEs was available for 32 cats (97%). The following AEs were recorded during PB treatment in 8/32 cats (25%): decreased activity (n = 4); weakness (n = 2); increased appetite (n = 2); decreased appetite (n = 2); increased water uptake (n = 1); weight gain (n = 1); and weight loss (n = 1).

Outcomes

Overall, no significant differences in any of the serum liver enzyme activities or other biochemical variables were detected before vs during PB treatment, with a median follow-up period of 11 months (range 1–62) (Table 2, Figure 1).

Table 2

Statistical analysis of the ratios for the different serum biochemistry variables evaluated

Variable	Sample size (n = 33)*	Median (range) pretreatment ratios	Median (range) post-treatment ratios	P value	Median (range) length of follow-up (months)	Additional comments
ALP	13 (40)	0.32 (0.22–0.83)	0.26 (0.03–1.19)	1	9 (1–45)	ALP was above the RI in four cats (12%) post-treatment 1, 3, 5 and 7 months, respectively, after initiation of PB therapy. In one cat ALP normalised during the second and third measurement, and no further work-up was performed. In a second cat there was no follow-up available after the increased measurement. In the third and fourth cats, ALP was measured above the RI at the two remaining follow-up measurements. In one of these cats, an abdominal ultrasound was performed and no structural liver pathology was identified
ALT	32 (96)	0.605 (0.13–1.45)	0.625 (0.27–2.51)	1	11.5 (1–62)	ALT was above the RI in five cats (15%) post-treatment, 1 month after initiation of PB therapy in two cats, and 4, 6 and 9 months, respectively, in the other three cats. In one cat, ALT normalised during the following measurement and an abdominal ultrasound identified no structural liver pathology. In three cats the increase in ALT was associated with a PB serum concentration >30 µg/ml for 2–3 measurements. ALT normalised after the PB dose was decreased (<30 µg/ml SC) in 2/3 cats. For the last cat, the PB dosage was decreased, but ALT remained increased. In the fifth cat, no follow-up blood sampling was available
AST	9 (28)	0.57 (0.38–1.11)	0.74 (0.5–1.76)	1	11 (1–24)	AST was above the RI in four cats (12%) post-treatment 1, 4, 6 and 9 months, respectively, after initiation of PB therapy. No cat showed clinical signs of liver pathology. In two cats, ALT was increased at the same time. In one cat, AST normalised during the next AST measurement 1 month later; abdominal ultrasound was performed at this time and was normal. In one cat, the increase in AST was associated with a PB serum concentration >30 µg/ml. After the PB, serum concentration was again <30 µg/ml; the increase in AST was no longer present. In two cats, no follow-up blood sampling was available
GGT	10 (30)	1 (0.3–1.2)	1 (0.3–1)	1	12 (1–24)	No cat showed an increase in GGT during the follow-up period
TBIL	14 (42)	0.6 (0–1.1)	0.375 (0–1)	1	12 (1–62)	No cat showed an increase in TBIL during the follow-up period
BA	8 (24)	0.25 (0–0.83)	0.2 (0.01–0.9)	1	16 (1–34)	No cat showed an increase in BA during the follow-up period
Glucose	25 (76)	0.86 (0.43–3.38)	0.88 (0.48–1.8)	1	13 (1–62)	No cat showed a decrease in glucose during the follow-up period
Albumin	26 (79)	0.88 (0.48–1.1)	0.83 (0.59–0.96)	0.48	12.5 (1–62)	No cat showed a decrease in albumin during the follow-up period
Urea	25 (76)	0.76 (0.46–1.36)	0.74 (0.54–1.3)	1	7 (1–62)	No cat showed a decrease in urea during the follow-up period
Creatinine	27 (82)	0.69 (0.4–1.2)	0.76 (0.5–1.16)	0.25	13 (1–62)	Creatinine was above the RI in two (6%) cats, 1 and 13 months after initiation of PB therapy, respectively. Both cats were diagnosed with idiopathic hypercalcaemia
Total protein	24 (73)	0.92 (0.72–1.1)	0.91 (0.69–1.26)	1	13.5 (1–62)	No cat showed a decrease in total protein during the follow-up period

The ratios were calculated by dividing the absolute value of the biochemistry parameter by the upper limit of the laboratory’s reference interval (RI; eg, aspartate transaminase [AST] is 36 U/l with an RI of >42 U/l. The ratio is calculated by dividing 36 by 42 with a result of 0.86)

Data are n (%)

ALP = alkaline phosphatase; ALT = alanine transaminase; GGT = gamma-glutamyl transferase; TBIL = total bilirubin; BA = bile acids

Figure 1

Median ratios of the serum biochemistry variables as presented in Table 2.

In one cat the baseline ratio concentration of serum AST, GGT and TBIL increased >1, and in a second cat the baseline ratio value of ALT increased >1. It was decided to include both cats as on follow-up blood sampling the concentration of all parameters was within the RIs.

In nine different cats the ratio of serum ALT, ALP and/or AST increased >1 during PB treatment. In only two of those cats was abdominal ultrasound (AUS) performed as a diagnostic to screen for underlying liver disease; no abnormalities were found on this examination.

In nine cats (27%) a PB serum concentration of >30 µg/ml was measured (median 35.22 μg/ml; range 31.1–50.89). Three (33%) of these nine cats showed a concurrent increase in ALT. One (11%) of these nine cats showed a concurrent increase in both ALT and ALP.

Discussion

PB is a potent ASD commonly used in cats with both structural and idiopathic epilepsy.³⁸ In this study, PB appeared to be a serum hepatic enzyme inducer in only a minority of cats, contrary to what is reported in dogs. This is important to consider as epileptic cats treated with PB and showing an increase in serum liver enzymes might have underlying liver pathology. Other side effects of PB administration, such as decreased activity, increased or decreased appetite, increased water uptake, weight gain and weight loss, were only noted in a minority of cats in the present study.

In dogs, one of the most reported AEs is the effect of PB on the liver. PB is a microsomal enzyme inducer, causing a proliferation of the smooth endoplasmic reticulum in hepatocytes, increasing liver weight and accelerating the metabolism of various drugs, including itself, and endogenous compounds via the induction of CYP450 enzymes.^21,39 These mechanisms also lead to increased serum liver enzyme activities. In most studies in dogs, PB is reported to increase mainly ALP and ALT,^{20,21,24–27,40} although two studies have also reported an increase in the activity of serum GGT.^21,41 BA, TBIL, ALB and total protein are not affected by PB administration in dogs.^21,26,32 Only one study reported decreased ALB in one dog treated with PB without having clinical signs of hepatopathy.²¹ Hepatotoxicity associated with PB treatment has been reported in dogs, although rarely.^{27,29,30,42,43} These dogs may suffer from lethargy, weakness, anorexia, coagulopathy, icterus and/or ascites.^29,30

To our knowledge, this is the first study to have specifically and primarily assessed serum biochemistry changes, with a major interest in serum liver enzyme changes, in cats with epilepsy receiving PB during their treatment. Records from multiple referral centres were reviewed and cats had a median follow-up of 11 months, from baseline bloodwork to last available bloodwork, which is a long period of time considering the lifespan of a cat. All cats were evaluated and treated by board-certified neurologists and residents.

The present study found no statistically significant differences for any of the serum liver enzymes when pretreatment serum liver enzyme activity was compared with activity during PB treatment. Other serological, pathological parameters associated with hepatopathy were also evaluated. AST, GGT, BA and TBIL can be increased in animals with hepatopathy.³¹ Glucose, albumin and total protein may be decreased in animals with hepatopathy.³¹ In previous studies, as well as this study, no significant changes in these parameters were detected in cats receiving PB.^{11,15,34–36} This is comparable to what is known in dogs. Six studies have reported on the effect of PB on serum liver enzymes in cats.^{8,11,15,34–36} Four studies found, respectively, an increase in ALT in 31%,¹⁵ 40%,³⁴ 5%¹¹ and 7%,⁸ and an increase in ALP in 11%,¹⁵ 4%³⁴ and 3%⁸ of cats treated with PB. An increase in AST in cats treated with PB has not been reported previously. Our study found an increase in ALT in 15%, in ALP in 12% and in AST in 12% of cats treated with PB (Table 2). The mean length of follow-up for the serum biochemistry analyses was specified as 3 weeks in two previous studies, compared with our mean follow-up period of 11 months.^35,36

Cats additionally treated with LEV and IMP were not excluded as neither drug affects hepatic function or routine laboratory parameters in cats,^8,12,44–48 and both can be safely used in animals with hepatic disease.⁹

Regarding PB serum concentrations in dogs, values >35 µg/ml increase the risk of hepatotoxicity.^9,29 In our study, 3/9 (33%) cats with a PB serum concentration of >30 µg/ml, which is above the advised therapeutic range,^12,13 showed increases in serum ALT or ALP above the RI. AUS is a good first diagnostic test when hepatic disease is suspected based on clinical signs and abnormalities on bloodwork.⁴⁹ Limitations of AUS are that hepatic parenchymal changes are not specific for any hepatic disease and that an unremarkable AUS does not rule out liver disease.⁴⁹ Histopathology is the most sensitive diagnostic available to rule out liver disease.⁴⁹ In the present study, only two cats with increased liver values underwent AUS; liver biopsies were not performed in any of these cats.

In previous studies, and in our study, no significant changes in serum creatinine concentrations were detected in cats receiving PB.^15,34–36 Creatinine concentrations were elevated above the RI in 6% of the cats in our study, but this was, after complete work-up by an ECVIM-CA diplomate, found to be related to idiopathic hypercalcaemia diagnosis in these cases. Creatinine was normal in both cats at baseline but was found to be increased during the study, together with poor control of their hypercalcaemia. One study reported azotaemia in two cats treated with PB, but this increase in serum creatinine was believed to be related to the development of chronic kidney disease at an older age.¹¹

Overall, the most common dose-dependent AE in cats is lethargy, followed by polyphagia, dermatological and neurological signs, clinical pathological abnormalities, weight loss and behavioural changes.^{5,8,13,18,50–52} Idiosyncratic AEs reported in cats treated with PB are clinicopathological abnormalities (thrombocytopenia, lymphopenia, anaemia, etc) and lymphoreticular and gastrointestinal signs, all of which are reversible with discontinuation of the drug.^{5,8,9,13,16,17,50,52} Based on a systematic review, PB is not only the most effective, but also the safest, ASD in cats.⁸ The majority of cats (83%) treated with PB did not show AEs, which is comparable with the 75% recorded in the present study.⁸ Owing to the retrospective nature of this study, without a standardised questionnaire for cat owners, this might be an underestimation.

A limitation of our study is its retrospective nature. This made it impossible to have a standardised approach to the work-up and follow-up for feline epileptic patients. Therefore, the evaluation and statistical analysis of the biochemistry parameters of interest were limited to a comparison between the baseline values and the last available post-treatment values for each case. Evaluation at fixed timepoints during PB treatment was not possible but would have been a more accurate approach. Another limitation related to the study design is the presence of variable follow-up times among cats, ranging from 1 to 62 months. This might have affected the outcome of this study as the long-term effect of PB on the biochemistry profile might have been missed in cats with only a short follow-up. However, we consider this limitation of minor concern given the fact that PB-related changes to the biochemistry profile are reported in dogs as early as 3 weeks,^27,53 and the median length of follow-up in our study was 11 months, which should be long enough to see PB treatment-related changes. For the same reason, not all laboratory variables of interest were available for every cat, which made the number of cases to evaluate per variable lower than the original 33 included cases. Future prospective studies with a standardised protocol are vital to confirm the findings of our study.

Conclusions

In the present study, the effect of PB treatment on serum liver enzymes and other serum biochemistry parameters of epileptic cats was evaluated. Based on our results, serum hepatic enzyme induction and risk of hepatotoxicity related to PB, in contrast to what has been reported in dogs, are unlikely to occur in cats. Also, for the other serum biochemistry parameters, no increase was recorded. In cases where liver enzymes are elevated, causes other than PB administration should be investigated. However, follow-up assessments of serum liver enzymes and PB serum concentrations are still advised, especially in cats with PB serum concentrations exceeding 30 µg/ml, and in cats with a clinical suspicion of liver disease.

Footnotes

Accepted: 12 July 2021

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Ethical approval

The work described in this manuscript involved the use of non-experimental (owned or unowned) animals. Established internationally recognised high standards (‘best practice’) of veterinary clinical care for the individual patient were always followed and/or this work involved the use of cadavers. Ethical approval from a committee was therefore not specifically required for publication in JFMS. Although not required, where ethical approval was still obtained, it is stated in the manuscript.

Informed consent

Informed consent (verbal or written) was obtained from the owner or legal custodian of all animal(s) described in this work (experimental or non-experimental animals, including cadavers) for all procedure(s) undertaken (prospective or retrospective studies). No animals or people are identifiable within this publication, and therefore additional informed consent for publication was not required.

ORCID iD

Michelle Hermans

Akos Pakozdy

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

Abstract

Objectives

Methods

Results

Conclusions and relevance

Keywords

Introduction

Materials and methods

Case selection

Outcome assessment

Statistical analysis

Results

Signalment and baseline characteristics

Outcomes

Discussion

Conclusions

Footnotes

Conflict of interest

Funding

Ethical approval

Informed consent

ORCID iD

References