Association between serum cobalamin and methylmalonic acid concentrations in dogs

The aim of this study was to evaluate the association between serum methylmalonic acid (MMA), a proposed marker of cellular cobalamin deficiency, and serum cobalamin concentrations in dogs. Serum samples from 555 dogs were grouped according to their serum cobalamin concentrations (<150 ng/L to 1000 ng/L). Additionally, serum samples were collected from 43 healthy dogs to calculate a reference interval for canine serum MMA. MMA was measured using a GC/MS method. Groups were compared using a Kruskal-Wallis test with Dunn's post test. Proportions of dogs above the upper limit of the reference interval were calculated and a χ2-test for trend was performed to evaluate the association between serum cobalamin and MMA concentrations. The reference interval for serum MMA was calculated to be 414.7-1192.5 nmol/L. Dogs with serum cobalamin concentrations <251 ng/L had significantly higher MMA concentrations (P<0.05) and the χ2-test for trend showed a trend for increasing serum MMA concentrations with decreasing serum cobalamin concentrations (P<0.0001). Additionally, a number of dogs with normal serum cobalamin concentrations had increased serum MMA concentrations, suggesting that some of these dogs may have cobalamin deficiency on a cellular level. Further studies are warranted to determine if these dogs should receive cobalamin supplementation.     

Serum folate,cobalamin, homocysteine and methylmalonic acid concentrations in pigs with acute,chronic or subclinical Lawsonia intracellularis infection

Lawsonia intracellularis is the causative agent of porcine proliferative enteropathy. The clinical presentation can be acute (i.e. proliferative hemorrhagic enteropathy, PHE), chronic (i.e. porcine intestinal adenomatosis, PIA) or subclinical. In humans with chronic enteropathies, low serum folate (vitamin B₉) and cobalamin (vitamin B₁₂) concentrations have been associated with increased serum concentrations of homocysteine and methylmalonic acid (MMA), which reflect the availability of both vitamins at the cellular level. The aim of this study was to evaluate serum folate, cobalamin, homocysteine and MMA concentrations in serum samples from pigs with PHE, PIA or subclinical L. intracellularis infection, and in negative controls. Serum folate, cobalamin, homocysteine and MMA concentrations differed significantly among pigs in the PHE, PIA, subclinical and negative control groups. Serum folate concentrations in the PHE and PIA groups were lower than in the subclinical and negative control groups, while serum cobalamin concentrations were lower in the PIA group than in other groups. Serum concentrations of homocysteine were higher in the PHE, PIA and subclinical groups than in the negative control group. Serum concentrations of MMA were higher in the subclinical and PIA groups than in the control group. These data suggest that pigs infected with L. intracellularis have altered serum cobalamin, folate, homocysteine and MMA concentrations.     

Serum cobalamin concentrations in dogs with leishmaniosis before and during treatment

Hypocobalaminemia in dogs is most commonly associated with gastrointestinal disorders leading to impaired absorption and utilization of cobalamin. The objectives of this study were to compare serum cobalamin concentrations between dogs with leishmaniosis and clinically healthy dogs, and to assess possible alterations of serum cobalamin concentrations in dogs with leishmaniosis at different timepoints during treatment. Fifty-five dogs with leishmaniosis and 129 clinically healthy dogs were prospectively enrolled. Diagnosis of leishmaniosis was based on clinical presentation, positive serology and microscopic detection of Leishmania amastigotes in lymph node aspiration smears. Twenty of the dogs with leishmaniosis were treated with a combination of meglumine antimonate and allopurinol for 28 days and serum cobalamin concentrations were measured in blood samples that were collected before initiation of treatment (timepoint 0) and on days 14 and 28. In order to estimate alterations of serum cobalamin concentrations during treatment, cobalamin concentrations were measured in blood samples from 20 out of 55 dogs with leishmaniosis at all timepoints. Serum cobalamin concentrations were significantly lower in dogs with leishmaniosis before treatment (median: 362 ng/L; IQR: 277−477 ng/L) compared to clinically healthy dogs (median: 470 ng/L; IQR: 367−632 ng/L; P = 0.0035). Serum cobalamin concentrations increased significantly in dogs with leishmaniosis on day 14 of treatment compared to timepoint 0 (P = 0.02).In the present study, serum cobalamin concentrations were significantly lower in dogs with leishmaniosis compared to clinically healthy dogs. In addition, there was an increase in serum cobalamin concentrations during treatment. The clinical significance of hypocobalaminemia in dogs with leishmaniosis remains to be determined.     

Serum alkaline phosphatase activity in Scottish Terriers versus dogs of other breeds

OBJECTIVE: To determine whether Scottish Terriers have higher serum alkaline phosphatase (ALP) activities and a higher prevalence of diseases commonly associated with high serum ALP activity than do dogs of other breeds. DESIGN: Retrospective case-control study. ANIMALS: 85 Scottish Terriers and 340 age-matched control dogs that were not Scottish Terriers. PROCEDURE: Medical records were reviewed, and data for year of evaluation, age, sex, breed, serum ALP activity, and final diagnosis were recorded. RESULTS: Scottish Terriers had a significantly higher mean serum ALP activity than did control dogs (1,520 U/L vs 306 U/L). Regardless of breed, dogs that had a disease commonly associated with high serum ALP activity had a significantly higher mean serum ALP activity than did dogs without such diseases (1,304 U/L vs 427 U/L). Scottish Terriers were 2.4 times as likely to have a disease commonly associated with high serum ALP activity than were control dogs, but Scottish Terriers with diseases commonly associated with high serum ALP activity had a significantly higher mean ALP activity than did control dogs with such diseases (2,073 U/L vs 909 U/L), and Scottish Terriers without such diseases had a significantly higher mean serum ALP activity than did control dogs without such diseases (1,349 U/L vs 228 U/L). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that Scottish Terriers have higher serum ALP activities than do dogs of other breeds. Although Scottish Terriers also have a higher prevalence of diseases associated with high serum ALP activity, this alone did not explain the higher mean serum ALP activity in the breed.     

Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in dogs with nonthyroidal disease

OBJECTIVE: To determine whether nonthyroidal disease of various causes and severity is associated with abnormalities in baseline serum concentrations of total thyroxine (T4), triiodothyronine (T3), free T4, or thyrotropin (thyroid-stimulating hormone [TSH]) in dogs believed to be euthyroid. DESIGN: Case-control study. ANIMALS: 223 dogs with confirmed nonthyroidal diseases and presumptive normal thyroid function, and 150 clinically normal dogs. PROCEDURE: Serum total T4, total T3, free T4, and TSH concentrations were measured in dogs with confirmed nonthyroidal disease. Reference ranges for hormone concentrations were established on the basis of results from 150 clinically normal dogs. RESULTS: In dogs with nonthyroidal disease, median serum concentrations of total T4, total T3, and free T4 were significantly lower than those in clinically normal dogs. Median serum TSH concentration in sick dogs was significantly greater than that of clinically normal dogs. When stratified by severity of disease (ie, mild, moderate, and severe), dogs with severe disease had low serum concentrations of total T4, total T3, or free T4 more commonly than did dogs with mild disease. In contrast, serum TSH concentrations were more likely to remain within the reference range regardless of severity of disease. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that serum total T4, free T4, and total T3 concentrations may be low (ie, in the hypothyroid range) in dogs with moderate to severe nonthyroidal disease. Serum TSH concentrations are more likely to remain within the reference range in sick dogs.     

Serum free and total iodothyronine concentrations in dogs with hyperadrenocorticism.

Serum concentrations of total and free thyroxine (T4 and FT4, respectively), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3) were measured in 42 dogs with hyperadrenocorticism, and were compared with values determined in clinically normal dogs. Mean total T4 concentration in dogs with hyperadrenocorticism (14.3 nmol/L) was significantly (P less than 0.001) lower than the normal value (25.7 nmol/L), with 38% of the dogs having low serum T4 concentration. Although 16 (38%) of the 42 dogs with hyperadrenocorticism had a high FT4 fraction, indicative of diminished serum T4 binding, normal FT4 concentration was found in only 6 of the 16 dogs (38%) with low total T4 values. Mean serum T3 concentration in dogs with hyperadrenocorticism (0.79 nmol/L) was also significantly (P less than 0.001) lower than the normal value (1.16 nmol/L), with 39% of the dogs having T3 values below the normal range. Individual T3-to-T4 and T3-to-FT4 ratios, indices of T3 production and/or clearance, were above the normal range in 29 and 24% of dogs with hyperadrenocorticism, respectively. Mean reverse T3 concentration in dogs with hyperadrenocorticism (0.17 nmol/L) was also significantly (P less than 0.001) lower than the normal mean value (0.39 nmol/L), with 48% of the dogs having reverse T3 values below the normal range. Of the 21 dogs in which all iodothyronines were measured, 6 (29%) had undetectable values for all hormones.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pathological changes in cobalt-supplemented and non-supplemented twin lambs in relation to blood concentrations of methylmalonic acid and homocysteine.

In a controlled field study of three years' duration we evaluated the effect of cobalt supplementation on pathological changes in cobalt/vitamin B12-deficient Texel twin lambs grazing the same cobalt-deficient pasture. Semi-quantitative evaluation of the histopathology of liver and brain was done on 44 sets of twins. Pathological changes were related to blood concentrations of vitamin B12, methylmalonic acid, and homocysteine. Lesions were mainly confined to the liver and brain. Acute hepatic changes were characterized by steatosis, hepatocytic degeneration, and single cell necrosis. Chronic changes consisted of bile duct proliferation, the presence of ceroid containing macrophages, and fibrosis in the portal triads. Many non-supplemented lambs showed polymicrocavitation and Alzheimer type II reaction in the brain. Polioencephalomalacia was observed in three non-supplemented lambs but was regarded as a secondary lesion. Our results indicate that the main lesions found in cobalt/vitamin B12-deficient lambs are acute and chronic hepatitis. These lesions were associated with low concentrations of vitamin B12 and high concentrations of methylmalonic acid and homocysteine in the blood. The liver lesions were also associated with polymicrocavitation of the brain, probably as morphological evidence of hepatoencephalopathy.     

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.     

Effect of strenuous exercise on urine concentrations of homovanillic acid, cortisol, and vanillylmandelic acid in sled dogs

OBJECTIVE: To determine whether prolonged exercise by conditioned sled dogs affects urine concentrations of homovanillic acid (a metabolite of dopamine), vanillylmandelic acid (a metabolite of norepinephrine and epinephrine), and cortisol. ANIMALS: 24 conditioned Alaskan sled dogs (2 to 8.5 years old) that were in training for a multiday endurance race. PROCEDURES: Voided urine samples were collected from 4 groups of dogs (randomly selected from 54 dogs) after no exercise (control group; n = 6 dogs), completion of a 160km run (group A; 3), completion of a 420-km run (group B; 7), and completion of a 560-km run (group C; 6). Urine cortisol concentrations were determined by use of an immunoassay technique; urine vanillylmandelic acid and homovanillic acid concentrations were measured via high-performance liquid chromatography. RESULTS: Compared with the control group, urine cortisol concentration in groups A, B, and C was significantly different (5.33 x 10(4) +/- 2.62 x 10(4) microg/dL vs 1.04 x 10(4) +/- 2.31 x 10(5) microg/dL, 8.88 x 10(4) +/- 5.49 x 10(4) microg/dL, and 6.31 x 10(4) +/- 5.09 x 10(4) microg/dL, respectively). Urine homovanillic acid concentration did not differ among the 4 groups. Vanillylmandelic acid was not detected in any urine samples. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that prolonged exercise by sled dogs did not affect urine homovanillic acid concentration but did increase urinary cortisol secretion, which is indicative of adrenocortical stimulation. The apparent lack of vanillylmandelic acid in voided urine samples requires further investigation.     

Serum total thyroxine and thyroid stimulating hormone concentrations in dogs with behavior problems

The aim of this case controlled study was to determine whether dogs with behavioral problems have evidence of abnormal thyroid function on routine screening tests for hypothyroidism. The hypothesis of the study was that thyroid function, as assessed by serum total thyroxine (TT4) and serum thyroid stimulating hormone (thyrotropin) (TSH) concentrations, is normal in most dogs with behavioral problems. Concentrations of TT4 and TSH in 39 dogs with behavior problems presenting to a veterinary behavior referral clinic (abnormal behavior group), were compared with TT4 and TSH concentrations in 39 healthy control dogs without behavior problems presenting to 5 community veterinary practices (control group). Dogs in the control group were matched for age and breed with the abnormal behavior group. Dogs with behavioral problems had higher TT4 concentrations than dogs without behavioral problems (t-test: t = 2.77, N = 39, P = 0.009), however none of the TT4 values were outside the reference range. There was no significant difference in TSH concentration between the 2 groups. Two dogs with behavior problems and 1 dog without behavior problems had results suggestive of hypothyroidism. All other dogs were considered to be euthyroid. There was no evidence to support a diagnosis of hypothyroidism in the majority of dogs with behavior problems in this study. The higher concentration of TT4 in dogs with behavior problems suggests, however, that alteration in thyroid hormone production or metabolism may occur in some dogs with behavior problems. Further studies that include additional indicators of thyroid status such as serum total triiodothyronine, serum, free thyroxine, and anti-thyroid antibody concentrations are necessary to further evaluate the significance of this finding.     

Epilepsy in Border Collies: Clinical Manifestation, Outcome, and Mode of Inheritance

Background: There is a lack of data on idiopathic epilepsy (IE) in Border Collies (BCs) in the veterinary literature.
Hypothesis: Genetic epilepsy occurs in BCs and is frequently characterized by a severe clinical course and poor response to medical treatment.
Animals: Forty-nine BCs diagnosed with IE.
Methods: Medical records, seizure data, treatment data, and pedigree information of affected dogs were collected. Cases were classified phenotypically as affected or not affected; mild, moderate, or severe clinical course; active epilepsy (AE) or remission; and drug resistant or not drug resistant.
Results: Clinical manifestations were classified as having a moderate (33%) or severe clinical course (49%), characterized by a high prevalence of cluster seizures and status epilepticus. Survival time was significantly decreased in dogs <2 years of age at seizure onset, and in dogs with a severe clinical course. Drug resistance was apparent in 71% of 24 dogs treated with ≥2 antiepileptic drugs. The epilepsy remission rate was 18%. Median age at onset was significantly higher and initial seizure frequency was significantly lower in dogs with remission compared with dogs with AE. Pedigree analyses indicated a strong genetic founder effect in the appearance of epilepsy, resembling autosomal recessive inheritance.
Conclusion and Clinical Importance: The present study confirms the occurrence of genetically mediated epilepsy with a frequent severe clinical course and drug resistance in BCs. The results provide information about the long-term prognosis of IE in BCs for veterinarians and concerned owners, and may benefit breeders as well.     

Serum total prostatic and non-prostatic acid phosphatase in healthy dogs and in dogs with prostatic diseases

Total acid phosphatase (TAP), prostatic acid phosphatase (PAP) and non-prostatic acid phosphatase (NPAP) serum concentrations were determined using a spectrophotometric technique in 52 healthy dogs, 15 male dogs suffering from non-prostatic diseases and in 19 dogs suffering from prostatic diseases (12 dogs with benign prostatic hypertrophy and seven dogs with prostatic adenocarcinoma). TAP, PAP and NPAP serum concentrations did not differ between normal male and normal female dogs. Dogs with prostatic adenocarcinoma had significantly higher TAP, PAP and NPAP serum concentrations than dogs with benign prostatic hypertrophy, normal dogs and dogs with non-prostatic disease. The authors conclude that low serum concentrations of TAP and PAP do not rule out prostatic adenocarcinoma in the dog, but elevated concentrations can be useful criteria for the diagnosis of canine prostatic cancer.     

Effect of hemodialysis on plasma amino acid concentrations in healthy dogs

OBJECTIVE: To characterize the effect of maintenance hemodialysis on plasma amino acid concentrations and to quantitate free amino acid losses into the dialysate during hemodialysis in healthy dogs. ANIMALS: 8 healthy adult dogs. PROCEDURE: Five dogs received hemodialysis treatments 3 times per week for 4 weeks. Plasma amino acid concentrations were evaluated once per week for 4 weeks in each of the 5 dogs prior to hemodialysis (time 0), 90 minutes during hemodialysis, and immediately after hemodialysis (180 minutes). Total free amino acid concentrations and plasma amino acid concentrations (time 0, 90 minutes, and 180 minutes) in the dialysate were evaluated in 3 dogs that received 1 hemodialysis treatment. RESULTS: Significant time versus week interactions with any plasma amino acid were not detected; however, significant decreases in all plasma amino acid concentrations measured were detected at the midpoint of dialysis (46 +/- 2%) and at the end of each dialysis session (38 +/- 2%). Mean (+/- SEM) total free amino acid loss into the dialysate was 2.7 +/- 0.2 g or 0.12 g/kg of body weight. CONCLUSIONS AND CLINICAL RELEVANCE: Hemodialysis is associated with significant alterations in plasma amino acid concentrations and loss of free amino acids into the dialysate. Loss of amino acids into the dialysate, coupled with protein calorie malnutrition in uremic patients, may contribute to depletion of amino acid stores.     

Review of cobalamin status and disorders of cobalamin metabolism in dogs

Disorders of cobalamin (vitamin B₁₂) metabolism are increasingly recognized in small animal medicine and have a variety of causes ranging from chronic gastrointestinal disease to hereditary defects in cobalamin metabolism. Measurement of serum cobalamin concentration, often in combination with serum folate concentration, is routinely performed as a diagnostic test in clinical practice. While the detection of hypocobalaminemia has therapeutic implications, interpretation of cobalamin status in dogs can be challenging. The aim of this review is to define hypocobalaminemia and cobalamin deficiency, normocobalaminemia, and hypercobalaminemia in dogs, describe known cobalamin deficiency states, breed predispositions in dogs, discuss the different biomarkers of importance for evaluating cobalamin status in dogs, and discuss the management of dogs with hypocobalaminemia.     

Serum cobalamin concentrations in healthy cats and cats with non-alimentary tract illness in Australia

Objective   To determine a reference range for serum cobalamin concentration in healthy cats in Australia using a chemiluminescent enzyme immunoassay and to prospectively investigate the prevalence of hypocobalaminaemia in cats with non-alimentary tract disease.
Design   Prospective study measuring serum cobalamin concentrations in clinically healthy cats and cats with non-alimentary tract illness.
Procedure   Blood was collected from 50 clinically healthy cats that were owned by staff and associates of Veterinary Specialist Services or were owned animals presented to Creek Road Cat Clinic for routine vaccination. Blood was collected from 47 cats with non-alimentary tract illness presented at either clinic. Serum cobalamin concentration was determined for each group using a chemiluminescent enzyme immunoassay.
Results   A reference range for Australian cats calculated using the central 95th percentile in the 50 clinically healthy cats was 345 to 3668 pg/mL. Median serum cobalamin concentration in 47 cats with non-alimentary tract illness (1186 pg/mL; range 117–3480) was not significantly different to the median serum cobalamin of the 50 healthy cats (1213 pg/mL, range 311–3688). Using the calculated reference range one sick cat with non-alimentary tract illness had a markedly low serum cobalamin concentration.
Conclusion   Although hypocobalaminaemia is uncommon in sick cats with non-alimentary tract illness in Australia, its occurrence in this study warrants further investigation.     

Serum and urine inorganic fluoride concentrations and urine oxalate concentrations following methoxyflurane anesthesia in the dog.

Plasma fluoride, urine fluoride and urine oxalate concentrations were measured before administering an anesthetic to 8 dogs, and at 0, 3, 9, 24, 48, and 72 hours following 1.5 hours of anesthesia with 1% methoxyflurane. Plasma and urine osmolalities were measured and compared with fluoride and oxalate values. Fluoride concentration increased in both plasma and urine following anesthesia when compared with the preanesthetic concentrations. Maximum mean plasma inorganic fluoride was 106.71 mumoles per liter (+/- 25.44 SE) at 9 hours after exposure to methoxyflurane was completed. By 72 hours after exposure to methoxyflurane the plasma fluoride concentration was 23.47 microM/L (+/- 5.74 SE). Mean urine inorganic fluoride concentration was highest at 9 hours after exposure to methoxyflurane and reached 6047.03 microM/L (+/- 1378.46 SE) as compared to the mean preanesthetic base-line concentration of 542.68 microM/L (+/- 132.93 SE), and the 72 hour mean urine fluoride concentration which was 1593.78 microM/L (+/- 579.46 SE). Urine oxalate concentrations, when compared with urine osmolality (mg/mOsm), increased throughout the study. The 72-hour concentration after exposure to methoxyflurane was 2.5 times the preanesthetic (mg/mOsm) oxalate concentration. Plasma osmolality did not change markedly during the study. Urine osmolalities varied between animals and collection times, but a consistent pattern did not occur. Clinical and laboratory signs of renal dysfunction were not observed in any animal during the study.     

Contribution of cobalamin analogues to plasma vitamin B12 concentrations in cattle

Plasma vitamin B12 concentrations in cattle were analysed by a radioisotope dilution assay using pig intrinsic factor and a microbiological assay using Euglena gracilis. Both assays provided similar results for samples of cattle plasma containing vitamin B12 concentrations ranging from 0.07 to 3.60 micrograms litre-1 (r = 0.95, P less than 0.001). The addition of excess cobinamide in the radioisotope dilution assay to block non-specific binding in the intrinsic factor preparation due to the presence of R-type binders, was used to determine the presence of cobalamin analogues. Cobalamin analogues accounted for up to 50 per cent of the total vitamin B12 concentration in samples of plasma from cows but were virtually undetectable in plasma from sheep.     

Validation of a radioassay for the determination of serum folate and cobalamin concentrations in dogs

Determinations of serum folate and cobalamin concentrations in dogs have proved of considerable value for the identification and characterisation of chronic small intestinal disorders, but the microbiological assays used are time-consuming and technically demanding. Dual isotope radio-assays are more convenient and have been developed for the determination of folate and cobalamin in human beings. This study has evaluated such an assay for the determination of serum folate and cobalamin concentrations in dogs by direct comparison with microbiological assays used previously. Assays were performed on samples from 77 dogs, including controls and animals with confirmed or suspected chronic small intestinal disease. Regression analysis demonstrated a significant relationship between the two assays for serum folate concentrations (R=0–85; P=0–0001) and a definite trend for radioassay to give lower results than bioassay. There was also a significant relationship between bioassay and radioassay data for serum cobalamin (R=0–91; P=0–0001) with comparable absolute values for these two assays. Radioassay of serum samples from 31 clinically healthy dogs gave control ranges of 3–7 to 8-8 4mUg/litre for folate and 205 to 490 ng/litre for cobalamin. These ranges were similar to those calculated by comparison with the established ranges for bioassay using regression analysis, which predicted ranges of 4-4 to 8-4 μg/litre and 217 to 398 ng/litre for radioassay of serum folate and cobalamin, respectively. These data indicate that a dual isotope radioassay of serum folate and cobalamin may be used for dogs, and emphasise the need for laboratories to validate and establish their own control ranges for different assays.     

Determination of grapiprant plasma and urine concentrations in horses

ObjectiveNon-steroidal anti-inflammatory drugs are inhibitors of cyclooxygenase (COX) in tissues and used as therapeutic agents in different species. Grapiprant, a member of the piprant class of compounds, antagonizes prostaglandin receptors. It is a highly selective EP4 prostaglandin E₂ receptor inhibitor, thereby limiting the potential for adverse effects caused by wider COX inhibition. The objectives of this study were to determine if the approved canine dose would result in measurable concentrations in horses, and to validate a chromatographic method of analysis for grapiprant in urine and plasma.Study designExperimental study.AnimalsA total of six healthy, adult mixed-breed mares weighing 502 ± 66 (397–600) kg and aged 14.8 ± 5.3 (6–21) years.MethodsMares were administered one dose of 2 mg kg^–1 grapiprant via nasogastric tube. Blood and urine samples were collected prior to and up to 48 hours after drug administration. Drug concentrations were measured using high-performance liquid chromatography.ResultsGrapiprant plasma concentrations ranged from 71 to 149 ng mL^–1 with the mean peak concentration (106 ng mL^–1) occurring at 30 minutes. Concentrations were below the lower limit of quantification (50 ng mL^–1) in four of six horses at 1 hour and in all six horses by 2 hours after drug administration. Grapiprant urine concentrations ranged from 40 to 4077 ng mL^–1 and were still detectable at 48 hours after administration.Conclusions and clinical relevanceCurrently, there are no published studies looking at the pharmacodynamics of grapiprant in horses. The effective concentration needed to control pain in dogs ranges 114–164 ng mL^–1. Oral administration of grapiprant (2 mg kg^–1) in horses did not achieve those concentrations. The dose was well tolerated; therefore, studies with larger doses could be conducted.