Serum Pancreatic Lipase Immunoreactivity Concentrations in Dogs Treated with Potassium Bromide and/or Phenobarbital

Potassium bromide, phenobarbital, or a combination of both is commonly used in the treatment of canine epilepsy. Several cases of clinical pancreatitis have been reported in dogs after treatment with potassium bromide, but the risk of elevated serum canine pancreatic lipase immunoreactivity concentrations in dogs treated with potassium bromide and/or phenobarbital has not previously been evaluated in a large group of dogs. This study suggests an increased risk for elevated serum canine pancreatic lipase immunoreactivity concentrations and possibly pancreatitis in dogs treated with potassium bromide or phenobarbital alone or in combination.     

Effect of timing of blood collection on serum phenobarbital concentrations in dogs with epilepsy

OBJECTIVE: To determine whether there are therapeutically relevant changes in serum phenobarbital concentrations throughout a daily dosing interval in epileptic dogs receiving phenobarbital for > or = 3 weeks. DESIGN: Prospective study. ANIMALS: 33 epileptic dogs receiving phenobarbital. PROCEDURE: Serum phenobarbital concentrations were measured at 0 hour (trough), 3 hours, and 6 hours after oral administration of phenobarbital in epileptic dogs that had received phenobarbital twice daily for a minimum of 3 weeks. For each dog, trough, 3-hour, and 6-hour serum phenobarbital concentrations were evaluated to determine whether they were within the same therapeutic category (lower, middle, or upper end of the therapeutic range of 15 to 45 micrograms/ml), or whether there was a > 30% change in serum concentrations throughout the day. RESULTS: Ninety-one percent (30/33) of dogs had trough, 3-hour, and 6-hour serum phenobarbital concentrations in the same therapeutic category. Only 9% (3/33) of dogs had trough, 3-hour, and 6-hour serum concentrations in different therapeutic categories with a > 30% change in concentrations throughout the day. Significant differences were not detected among mean serum phenobarbital concentrations when comparing the trough, 3-hour, and 6-hour samples for all dogs. CONCLUSIONS AND CLINICAL RELEVANCE: There is no therapeutically relevant change in serum phenobarbital concentrations throughout a daily dosing interval in most epileptic dogs. Therefore, timing is not important when collecting blood samples to measure serum phenobarbital concentrations in most epileptic dogs treated long-term with phenobarbital.     

Effects of phenobarbital treatment on serum thyroxine and thyroid-stimulating hormone concentrations in epileptic dogs.

OBJECTIVE: To determine whether phenobarbital treatment of epileptic dogs alters serum thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations. DESIGN: Cross-sectional study. ANIMALS: 78 epileptic dogs receiving phenobarbital (group 1) and 48 untreated epileptic dogs (group 2). PROCEDURE: Serum biochemical analyses, including T4 and TSH concentrations, were performed for all dogs. Additional in vitro analyses were performed on serum from healthy dogs to determine whether phenobarbital in serum interferes with T4 assays or alters free T4 (fT4) concentrations. RESULTS: Mean serum T4 concentration was significantly lower, and mean serum TSH concentration significantly higher, in dogs in group 1, compared with those in group 2. Thirty-one (40%) dogs in group 1 had serum T4 concentrations less than the reference range, compared with 4 (8%) dogs in group 2. All dogs in group 2 with low serum T4 concentrations had recently had seizure activity. Five (7%) dogs in group 1, but none of the dogs in group 2, had serum TSH concentrations greater than the reference range. Associations were not detected between serum T4 concentration and TSH concentration, age, phenobarbital dosage, duration of treatment, serum phenobarbital concentration, or degree of seizure control. Signs of overt hypothyroidism were not evident in dogs with low T4 concentrations. Addition of phenobarbital in vitro to serum did not affect determination of T4 concentration and only minimally affected fT4 concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Clinicians should be aware of the potential for phenobarbital treatment to decrease serum T4 and increase TSH concentrations and should use caution when interpreting results of thyroid tests in dogs receiving phenobarbital.     

Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in epileptic dogs treated with anticonvulsants.

OBJECTIVE: To determine whether administration of phenobarbital, potassium bromide, or both drugs concurrently was associated with abnormalities in baseline serum total thyroxine (T4), triiodothyronine (T3), free T4, or thyrotropin (thyroid-stimulating hormone; TSH) concentrations in epileptic dogs. DESIGN: Prospective case series. ANIMALS: 78 dogs with seizure disorders that did not have any evidence of a thyroid disorder (55 treated with phenobarbital alone, 15 treated with phenobarbital and bromide, and 8 treated with bromide alone) and 150 clinically normal dogs that were not receiving any medication. PROCEDURE: Serum total T4, total T3, free T4, and TSH concentrations, as well as serum concentrations of anticonvulsant drugs, were measured in the 78 dogs with seizure disorders. Reference ranges for hormone concentrations were established on the basis of results from the 150 clinically normal dogs. RESULTS: Total and free T4 concentrations were significantly lower in dogs receiving phenobarbital (alone or with bromide), compared with concentrations in clinically normal dogs. Administration of bromide alone was not associated with low total or free T4 concentration. Total T3 and TSH concentrations did not differ among groups of dogs. CLINICAL IMPLICATIONS: Results indicate that serum total and free T4 concentrations may be low (i.e., in the range typical for dogs with hypothyroidism) in dogs treated with phenobarbital. Serum total T3 and TSH concentrations were not changed significantly in association with phenobarbital administration. Bromide treatment was not associated with any significant change in these serum thyroid hormone concentrations.     

Changes in serum thyroxine and thyroid-stimulating hormone concentrations in epileptic dogs receiving phenobarbital for one year

A multicentric prospective study was conducted to monitor the effect of phenobarbital on serum total thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations in epileptic dogs. Serum T4 concentrations were determined for 22 epileptic dogs prior to initiation of phenobarbital therapy (time 0), and 3 weeks, 6 months, and 12 months after the start of phenobarbital. Median T4 concentration was significantly lower at 3 weeks and 6 months compared to time 0. Thirty-two percent of dogs had T4 concentrations below the reference range at 6 and 12 months. Nineteen of the 22 dogs had serum TSH concentrations determined at all sampling times. A significant upward trend in median TSH concentration was found. No associations were found between T4 concentration, dose of phenobarbital, or serum phenobarbital concentration. No signs of overt hypothyroidism were evident in dogs with low T4, with one exception. TSH stimulation tests were performed on six of seven dogs with low T4 concentrations at 12 months, and all but one had normal responses. In conclusion, phenobarbital therapy decreased serum T4 concentration but did not appear to cause clinical signs of hypothyroidism. Serum TSH concentrations and TSH stimulation tests suggest that the hypothalamic-pituitary-thyroid axis is functioning appropriately.     

Hepatotoxicity of phenobarbital in dogs: 18 cases (1985-1989).

The medical records of 18 dogs that had hepatic disease and received phenobarbital as an anticonvulsant for 5 to 82 months were reviewed. Clinical signs included sedation and ataxia in all dogs, 5 dogs were also anorectic, 2 had coagulopathy, 3 were icteric, and 5 had ascites. Serum biochemical analysis revealed serum albumin concentration less than or equal to 2.2. g/dl in 12 dogs, serum alkaline phosphatase activity greater than or equal to 169 U/L in 18 dogs, serum alanine transaminase activity greater than or equal to 57 U/L in 15 dogs, and total bilirubin concentration greater than or equal to 1 mg/dl (in the absence of lipemia) in 7 dogs. Serum phenobarbital concentration was greater than or equal to 40 micrograms/ml in 12 of 17 dogs. Sulfobromophthalein excretion was prolonged in 8 of 10 dogs. Preprandial serum bile acid concentrations were high in 8 of 10 dogs, and 2-hour postprandial serum bile acid concentrations were high in 9 of 10 dogs. Two of 4 dogs tested had resting plasma ammonia concentrations greater than 200 mg/dl. An ammonia tolerance test was performed on 2 other dogs; both had ammonia concentration greater than or equal to 200 mg/dl in the plasma 30 minutes after receiving 100 mg of ammonium chloride/kg of body weight, PO. Nine dogs died, 1 was euthanatized, and necropsies were performed on these 10 dogs. Biopsies and necropsies of 6 dogs revealed chronic hepatic fibrosis with nodular regeneration (cirrhosis). One dog had hepatocellular carcinoma and mild cirrhosis. In 1 dog, after phenobarbital had been withheld, necropsy revealed complete recovery of the previously observed lesions.     

Efficacy of primidone in dogs with seizures unresponsive to phenobarbital

Fifteen epileptic dogs had been treated with high dosages of phenobarbital but had not achieved adequate control of their seizures. Their treatment was switched to comparable and higher dosages of primidone. Serum concentrations of phenobarbital were measured in all dogs before and after primidone therapy was initiated, to ensure that the primidone dosage achieved comparable or higher values when derived from primidone. Only one dog experienced improvement in seizure control, indicating that there is no advantage to the use of primidone over the use of phenobarbital for the control of seizures in most dogs.     

Pancreatitis associated with potassium bromide/phenobarbital combination therapy in epileptic dogs

In a retrospective study, at least 10% of dogs receiving potassium bromide/phenobarbital combination therapy, compared with 0.3% of dogs receiving phenobarbital monotherapy, had probable pancreatitis. Pancreatitis may be a more frequent and more serious adverse effect of potassium bromide/phenobarbital combination therapy than has been reported previously.     

Serum triglyceride concentrations in Miniature Schnauzers with and without a history of probable pancreatitis

Background: The association between hypertriglyceridemia and pancreatitis remains obscure in dogs. A possible role of hypertriglyceridemia as a cause of pancreatitis in Miniature Schnauzers has been suspected. Hypothesis/Objectives: To compare serum triglyceride concentrations between Miniature Schnauzers with and without a recent history of pancreatitis. Animals: Seventeen Miniature Schnauzers with a history of pancreatitis (group 1) and 34 age‐matched Miniature Schnauzers without a history of pancreatitis (group 2) were prospectively enrolled. Methods: Prospective case‐control study. Two samples were collected from each of the 17 Miniature Schnauzers with pancreatitis: 1 during pancreatitis and 1 after clinical and biochemical resolution of pancreatitis. Serum triglyceride and cholesterol concentrations were compared between group 1 (after resolution of pancreatitis) and group 2. Results: Miniature Schnauzers in group 1 were significantly more likely to have hypertriglyceridemia (>108 mg/dL) (71%) after resolution of pancreatitis than Miniature Schnauzers in group 2 (33%; odds ratio = 5.02; 95% confidence interval = 1.4–17.8; P= .0163). Serum triglyceride concentrations were significantly higher in dogs of group 1 (median: 605.0 mg/dL) after resolution of pancreatitis than in dogs of group 2 (median: 73.5 mg/dL; P= .002). Conclusions and Clinical Importance: Miniature Schnauzers with a history of pancreatitis were 5 times more likely to have hypertriglyceridemia than controls. Hypertriglyceridemia might be associated with the development of pancreatitis in some dogs of this breed. Additional studies are needed to further clarify the role of hypertriglyceridemia in the development of pancreatitis in Miniature Schnauzers as well as other dog breeds.     

Levetiracetam as an adjunct to phenobarbital treatment in cats with suspected idiopathic epilepsy

OBJECTIVE: To assess pharmacokinetics, efficacy, and tolerability of oral levetiracetam administered as an adjunct to phenobarbital treatment in cats with poorly controlled suspected idiopathic epilepsy. DESIGN-Open-label, noncomparative clinical trial. ANIMALS: 12 cats suspected to have idiopathic epilepsy that was poorly controlled with phenobarbital or that had unacceptable adverse effects when treated with phenobarbital. PROCEDURES: Cats were treated with levetiracetam (20 mg/kg [9.1 mg/lb], PO, q 8 h). After a minimum of 1 week of treatment, serum levetiracetam concentrations were measured before and 2, 4, and 6 hours after drug administration, and maximum and minimum serum concentrations and elimination half-life were calculated. Seizure frequencies before and after initiation of levetiracetam treatment were compared, and adverse effects were recorded. RESULTS: Median maximum serum levetiracetam concentration was 25.5 microg/mL, median minimum serum levetiracetam concentration was 8.3 microg/mL, and median elimination half-life was 2.9 hours. Median seizure frequency prior to treatment with levetiracetam (2.1 seizures/mo) was significantly higher than median seizure frequency after initiation of levetiracetam treatment (0.42 seizures/mo), and 7 of 10 cats were classified as having responded to levetiracetam treatment (ie, reduction in seizure frequency of >or=50%). Two cats had transient lethargy and inappetence. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that levetiracetam is well tolerated in cats and may be useful as an adjunct to phenobarbital treatment in cats with idiopathic epilepsy.     

Bromide toxicosis (bromism) in a dog treated with potassium bromide for refractory seizures.

A 4-year-old German Shepherd Dog was evaluated because of chronic hind limb lameness and recurrent seizures. Diagnostic evaluation of the dog confirmed rheumatoid arthritis and idiopathic epilepsy. The rheumatoid arthritis was treated with prednisone and piroxicam. The seizures were treated with phenobarbital plus clonazepam. The seizures were refractory and potassium bromide was substituted for clonazepam. The dog was reevaluated 4 months after initiation of potassium bromide treatment because of recurrence of arthritis signs. During hospitalization, the dog had neurologic signs, which progressed from depression to recumbency and stupor. Anisocoria, muscle pain, and hyporeflexia were noticed. Bromide toxicosis was diagnosed on the basis of toxic serum bromide concentration (2.7 mg/ml; therapeutic range, 1.0 to 2.0 mg/ml). Following cessation of potassium bromide treatment, the neurologic signs resolved. The seizures recurred 6 weeks after potassium bromide was discontinued. Bromide treatment was reinitiated at half the initial dosage. After 6 weeks, the serum bromide concentration was 1.9 mg/ml, and no seizures had been reported by the dog's owners. Therapeutic serum bromide concentrations in dogs has been reported to be 0.5 to 2.3 mg/ml. The serum bromide concentration at which toxic signs are expected is variable in human beings because individuals differ in their tolerance of the drug. Clinical trials are necessary to determine the toxic serum bromide concentrations in dogs. This case of bromism in a dog suggests that the dosage of potassium bromide should be based on serial measurement of serum bromide concentrations.     

Investigation of hypertriglyceridemia in healthy Miniature Schnauzers

BACKGROUND: Idiopathic hypertriglyceridemia has been reported in Miniature Schnauzers (MS). However, studies investigating the prevalence of this disorder in a large population of MS are lacking. HYPOTHESIS: Hypertriglyceridemia is prevalent in healthy MS. ANIMALS: This study used 192 healthy MS and 38 healthy dogs of other breeds (control dogs). METHODS: Serum triglyceride and cholesterol concentrations were measured and statistically compared in both the MS and control group. Dogs were categorized based on their age, and median serum triglyceride concentrations were compared among different age groups. RESULTS: A total of 63 (32.8%) of the 192 MS had serum triglyceride concentrations above the reference range. In contrast, of the 38 control dogs, only 2 (5.3%) had serum triglyceride concentrations above the reference range. The median serum triglyceride concentration in MS was 73.5 mg/dL, which was significantly higher as compared to that of the control group (median, 55 mg/dL; P = .0005). Serum cholesterol concentration was above the reference range in 9 (9.0%) of 100 MS and in 2 (5.3%) of the control dogs. Mean serum cholesterol concentrations were not significantly different between the 2 groups (P = .1374). Median serum triglyceride concentrations in MS increased significantly with age (P < .0001), and there was a significant positive correlation between serum triglyceride concentrations and age (Spearman r = 0.47; P < .0001). There was no difference in serum triglyceride concentrations between male and female MS (P = .48). CONCLUSION: Healthy MS have a high prevalence of hypertriglyceridemia as compared to healthy dogs of other breeds. Both the prevalence and severity of hypertriglyceridemia increase with age.     

Low concentrations of cerebrospinal fluid GABA correlate to a reduced response to phenobarbital therapy in primary canine epilepsy

In this study, we investigated whether pretreatment cerebrospinal fluid (CSF) neurotransmitter concentrations of gamma-aminobutyric acid (GABA) and glutamate (GLU) were correlated with response to phenobarbital treatment in dogs with primary epilepsy. Eleven untreated dogs, 6 males and 5 females, with a median age of onset of seizures of 3 years (range: 0.5-5 years) were selected for therapy based on progressive or serious seizure patterns. The median interval between the first observed seizure and start of phenobarbital therapy was 485 days (range: 101-1,765 days). All dogs were purebred, with the exception of I male dog. Oral phenobarbital was started at 2.5 mg/kg every 12 hours. Trough serum phenobarbital concentrations were measured at 15, 45, 90, 180, 360, 540, and 720 days after the start of treatment. There was no difference in the mean trough serum concentration or in the mean number of seizures recorded between each time period of phenobarbital measurement over the 2-year evaluation. No correlation was found between CSF GLU, GABA, or GLU: GABA ratio and the total number of seizures recorded before or after initiation of phenobarbital therapy. Lower CSF GABA concentration, however, was correlated with a lower seizure frequency difference (the total number of seizures before phenobarbital therapy minus the total number of seizures after phenobarbital therapy for an identical time period of evaluation) and lower percentage reduction in seizures: ([total number of seizures before phenobarbital therapy minus the total number of seizures after phenobarbital therapy] divided by the total number of seizures before phenobarbital therapy) x 100. There was no correlation between CSF GLU and the seizure frequency difference and percentage reduction in seizures. A negative correlation between the CSF GLU:GABA ratio and seizure frequency difference was found. Thus, dogs with an initial lower CSF GABA concentration before phenobarbital therapy did not respond as well as did dogs with a higher CSF GABA concentration.     

Effects of acute pancreatitis on circulating lipids in dogs

Effects of acute pancreatitis on circulating lipids in dogs were evaluated by comparing the serum cholesterol and triglyceride concentrations and plasma lipoprotein electrophoretic patterns of 4 dogs with experimentally induced pancreatitis (EIP), 2 (healthy) sham-operated control (SOC) dogs, and 4 dogs with naturally acquired pancreatitis (NAP) with the concentrations and patterns of 23 healthy, nonoperated control (HNC) dogs. Blood samples were collected once from HNC dogs, 1 to 3 times during the course of the disease in dogs with NAP, and prior to and at 6, 12, 24, 48, 72, and 96 hours after induction of pancreatitis in dogs with EIP or after the sham operation in the SOC dogs. The dogs with EIP did not have turbid serum and did not develop hypercholesterolemia or hypertriglyceridemia. Three of the dogs with NAP had turbid serum and hypertriglyceridemia, and 3 had hypercholesterolemia. The electrophoretic tracings of HNC dogs had predominant alpha-1 peaks and small beta peaks; 2 of the HNC dogs also had small alpha-2 peaks. The tracings of dogs with EIP were similar to those of HNC dogs until 48 to 72 hours after induction of pancreatitis, when dogs with EIP developed increased beta lipoproteins, decreased alpha-1 lipoproteins, and movement of lipoproteins into the alpha-2 zone. The tracings of SOC dogs were similar to those of HNC dogs at all times. Compared with HNC dogs, dogs with NAP all had increased beta lipoproteins, and 2 had decreased alpha-2 lipoproteins. Two dogs with NAP had additional lipoprotein alterations, unlike any seen in dogs with EIP.     

Therapeutic serum concentrations of primidone and its metabolites, phenobarbital and phenylethylmalonamide in epileptic dogs

Fifteen dogs with idiopathic epilepsy were included in a 9-month clinical trial to determine the therapeutic serum concentrations of primidone and its active metabolites, phenobarbital and phenylethylmalonamide. Dogs with a seizure frequency greater than 1/mo or with a record of multiple seizures greater than 1/day were chosen for the study. Each dog was given primidone 3 times daily at dosages intended to maximize seizure control and to minimize undesired side effects. Maintenance period blood samples were taken from fasted dogs 7 hours after dosing in the 3rd, 5th, 7th, and 9th months of the trial to determine therapeutic serum concentrations of primidone and its metabolites. Two blood samples also were taken from all dogs 7 hours after dosing, during an enforced drowsy period, to establish upper limits of desirable serum concentrations of the drug. Seizure frequencies during the trial were controlled in 13 dogs, 7 of which had no seizures during the 9-month trial. The mean percentage reduction in seizure frequency from pretrial frequency was 85%. Two dogs appeared refractory to primidone therapy. Serum phenobarbital was the best metabolite of primidone to use to assess therapeutic serum concentrations. The therapeutic antiepileptic serum concentration of phenobarbital was found to be between 25 and 40 micrograms/ml of serum. Serum phenobarbital concentrations greater than 40 micrograms/ml resulted in side effects in most dogs.     

Assessment of the use of plasma and serum chloride concentrations as indirect predictors of serum bromide concentrations in dogs with idiopathic epilepsy

BACKGROUND: Bromide (BR) administration causes pseudohyperchloremia when plasma or serum chloride (Cl-) concentrations are determined with commonly available automated analytical assays. In humans receiving BR, it has been previously demonstrated that the plasma Cl- concentration is a useful indirect estimator of the measured BR concentration. OBJECTIVE: The objective of this study was to determine if the magnitude of pseudohyperchloremia seen in epileptic dogs treated with BR could be used as a predictor of the measured serum BR concentration. METHODS: Plasma and serum Cl- concentrations, analyzed by ion-specific electrode (ISE) and colorimetric techniques, and serum BR concentrations, determined using the gold-trichloride assay, were simultaneously determined in 88 blood samples from dogs with idiopathic epilepsy that were treated with BR. RESULTS: For all methods used to quantify Cl- concentrations, there were significant (P < .0001) linear relationships between BR and Cl- concentrations. Linear relationships between BR and Cl- concentrations were significantly different (P < .0001) between blood samples from dogs obtained during routine therapeutic monitoring and those obtained during emergency hospital admissions. Calculated 95% prediction intervals for future values of BR using measured Cl- concentrations contained considerable error. Plasma Cl- values determined with ISE generally provided the best prediction of serum BR concentrations. Agreement between the measured BR and Cl- using all Cl- assay techniques was moderate, but was statistically significant only when Cl- was assayed in plasma using one ISE method. CONCLUSIONS: The pseudohyperchloremia observed in epileptic dogs receiving BR is an inadequate indirect estimator for the measured BR concentration, although in certain clinical situations identified through construction of a clinical decision tree, the measured Cl- value can be used to guide general therapeutic decisions regarding alterations in BR therapy. Optimal tailoring of BR therapy in dogs with idiopathic epilepsy should be based on results of therapeutic monitoring of BR concentrations.     

Lipids and lipoproteins in normal dogs and in dogs with secondary hyperlipoproteinemia.

Concentrations of serum cholesterol, triglyceride, and free glycerol were neasured, and serum lipoprotein electrophoresis was performed in normal dogs and in dogs with hypothyroidism, diabetes mellitus, and acute pancreatitis. Twelve privately owned dogs and 20 Basset Hounds from a research colony served as normal subjects. Privately owned had higher serum lipid concentrations than did research dogs. On electrophorisis of normal dog serum, lipoprotein bands were detected at the beta, pre-beta, alpha-2, and alpha-1 positions. Hypercholesterolemia was associated with increased intensity of the alpha-2-lipoprotein band, and hypertriglyceridemia occurred with increased lipoprotein at the origin, or the beta or pre-beta positions. Hypothyroid dogs had normal lipid values and lipoprotein electrophoretic patterns, hypercholesterolemia with increased intensity of the alpha-2-lipoprotein band, or hypercholesterolemia and hypertiglyceridemia with prominent beta-, pre-beta, and alpha-2-lipoprotein electrophoretic patterns were changed to near-normal values after levothyroxine administration. Diabetic dogs had increased serum cholesterol and triglyceride content and a predominance of lower density lipoproteins, as detected by electrophoresis. Insulin therapy caused the lipid concentrations to decrease and the electrophoretic pattern to revert to near normal. Dogs with acute pancreatitis had moderately increased serum lipid content and electrophoretic patterns characterized by increased intensity of the beta-lipoprotein band and by altered migration of alpha-1-lipoproteins.     

Thyroid function and serum hepatic enzyme activity in dogs after phenobarbital administration

Phenobarbital is the drug of choice for control of canine epilepsy. Phenobarbital induces hepatic enzyme activity, can be hepatotoxic, and decreases serum thyroxine (T4) concentrations in some dogs. The duration of liver enzyme induction and T4 concentration decreases after discontinuation of phenobarbital is unknown. The purpose of this study was to characterize the changes in serum total T4 (TT4), free T4 (FT4), thyroid-stimulating hormone (TSH), cholesterol and albumin concentrations, and activities in serum of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) after discontinuation of long-term phenobarbital administration in normal dogs. Twelve normal dogs were administered phenobarbital at a dosage of approximately 4.4-6.6 mg/kg PO q12h for 27 weeks. Blood was collected for analysis before and after 27 weeks of phenobarbital administration and then weekly for 10 weeks after discontinuation of the drug. The dogs were clinically normal throughout the study period. Serum ALT and ALP activity and TSH and cholesterol concentrations were significantly higher than baseline at week 27. Serum T4 and FT4 were significantly lower. Serum albumin and GGT were not changed from baseline at week 27. Changes in estimate of thyroid function (TT4, FT4, TSH) persisted for 1-4 weeks after discontinuation of phenobarbital, whereas changes in hepatic enzyme activity (ALT, ALP) and cholesterol concentration resolved in 3-5 weeks. To avoid false positive results, it is recommended that thyroid testing be performed at least 4 weeks after discontinuation of phenobarbital administration. Elevated serum activity of hepatic enzymes 6-8 weeks after discontinuation of phenobarbital may indicate hepatic disease.     

Therapeutic efficacy of phenobarbital and primidone in canine epilepsy: a comparison

The efficacy of phenobarbital and primidone against canine epilepsy was compared in a controlled study. Thirty-five dogs showing generalized tonic-clonic seizures (grand mal), treated for a minimum of 6 months, were included in the study; fifteen of these were treated with phenobarbital, the other twenty with primidone. Both drugs were dosed according to the clinical requirement; the daily doses ranged from 5-17 mg/kg phenobarbital and from 17-70 mg/kg primidone. The plasma concentrations of phenobarbital, or of primidone and its metabolites phenobarbital and phenylethylmalondiamide (PEMA), were routinely monitored. Complete control of tonic-clonic seizures for 6 months, at least, was attained in six out of fifteen dogs of the phenobarbital group, and in five out of twenty dogs in the primidone group. A further six dogs on phenobarbital, and seven dogs on primidone, were classified as 'improved', i.e. the rate of seizures was reduced by at least 50%. The rest of the dogs were not improved by the treatment. The difference between the efficacy of phenobarbital and primidone was not significant, but primidone gave rise to signs of liver toxicity in fourteen out of twenty dogs, as indicated by considerable elevations of liver enzyme values (alanine transferase, glutamate dehydrogenase, alkaline phosphatase). Phenobarbital is, therefore, regarded as the drug of first choice for the treatment of canine epilepsy.     

Serum liver enzyme activities in healthy Miniature Schnauzers with and without hypertriglyceridemia

OBJECTIVE: To determine whether hypertriglyceridemia in healthy Miniature Schnauzers is associated with high serum liver enzyme activities. DESIGN: Cross-sectional study. ANIMALS: 65 Miniature Schnauzers with serum triglyceride concentrations within the reference range (group 1), 20 Miniature Schnauzers with slightly high serum triglyceride concentrations (group 2), and 20 Miniature Schnauzers with moderately to severely high serum triglyceride concentrations (group 3). PROCEDURES: Questionnaires regarding each dog's medical history were completed, and serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and G-glutamyltransferase (GGT) activities were measured. RESULTS: Median serum ALP activity was significantly higher in group 3 than in group 1 or 2 dogs, but was not significantly higher in group 2 than in group 1 dogs. Median serum ALT activity was significantly higher in group 3 than in group 1 dogs, but was not significantly different between any of the other groups. Compared with group 1 dogs, group 2 and 3 dogs were significantly more likely to have high serum ALP activity (odds ratio, 26.2 and 192.6, respectively). Group 3 dogs also were significantly more likely to have high serum ALT activity (odds ratio, 8.0), serum AST activity (odds ratio, 3.7), and serum GGT activity (odds ratio, 11.3), compared with group 1 dogs. Group 3 dogs were significantly more likely (odds ratio, 31.0) to have > or = 2 high serum liver enzyme activities than were group 1 dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that moderate to severe hypertriglyceridemia was associated with high serum liver enzyme activities in Miniature Schnauzers.