Pathology of gastritis and gastric ulceration in the horse. Part 1: Range of lesions present in 21 mature individuals

Reasons for performing study: Gastric ulceration is now widely recognised as an important disease in high performance horses. Little is known about gastric histopathology in healthy or diseased animals; a comprehensive assessment would enhance interpretation of gross findings through assessment of their accuracy and allow for identification of lesion variety and pathogenesis in different anatomical regions of the stomach. Objectives: To investigate the true extent and variety of gastric lesions in a mixed population of mature horses at post mortem. Methods: Stomachs were removed from a mixed population of 21 horses at post mortem. Mucosal abnormalities were recorded in photographic and written form. Representative samples from all gross lesions were taken for histopathology and processed routinely. Special stains including Gram, PAS and Warthin Starry, were used when appropriate. Pathological classification of lesion type using both gross and histological appearances was performed. Results: Classification of lesions within the squamous region included hyperkeratosis, punctate scars, diffuse erosions/ulcerations and margo injuria; and within the glandular region, hyperaemia, focal erosions and ulcerations. Glandular metaplasia was recognised for the first time in the equine stomach. No Helicobacter‐like organisms were detected in association with lesion development. Conclusions and potential relevance: This study used gross and histological examination to highlight the large variety of naturally occurring gastric lesions in a mixed population of horses. Analysis of the pathogenesis of lesion development is now possible. Further research regarding the range of pathology in larger, more diverse groups of horses is required.     

The prevalence and anatomical distribution of equine gastric ulceration syndrome (EGUS) in 201 horses in Denmark

Reasons for performing study: The prevalence (up to 93% in Thoroughbred racehorses) and severity of equine gastric ulceration syndrome (EGUS) have been correlated with the type of training and associated management practices. However, there have been few reports to confirm these findings in nonracehorses in Europe. Objectives: To describe the prevalence, anatomical distribution, severity and number of gastric ulceration lesions in a population of Danish pleasure horses; and to investigate differences for groups based on age, breed type and workload. Methods: A total of 201 horses not in active race‐training, age 7 months‐27 years, were evaluated, representing 23 different stables from all 5 regions of Denmark. These horses were considered to be healthy by the owner and not on veterinary treatment for EGUS. Endoscopically observed ulcer lesion scores were based on the number present (0–4) and severity (0–5). The presence or absence of ulcers in the glandular and/or nonglandular regions of the stomach was recorded and which site the most severe ulcers were found. Results: The prevalence of EGUS severity score ≥2 was 53%. The most severe lesions were commonly observed at the margo plicatus. Although older horses were not more likely to be affected by clinically significant EGUS they were more likely to have lesions in both the glandular and nonglandular regions. Differences in location of EGUS lesions were identified in different age groups, breed types and in horses exposed to different levels of work. Conclusion and potential relevance: This study confirms that gastric ulceration can be prevalent in a group of apparently clinically normal horses, not in intensive work. Further investigation of reasons for differences in EGUS location between different populations may aid toward the development of novel preventive measures.     

Distribution of flunixin meglumine and firocoxib into aqueous humor of horses

Background: Nonsteroidal anti‐inflammatory drugs (NSAIDs) are commonly used systemically for the treatment of inflammatory ocular disease in horses. However, little information exists regarding the ocular penetration of this class of drugs in the horse. Objective: To determine the distribution of orally administered flunixin meglumine and firocoxib into the aqueous humor of horses. Animals: Fifteen healthy adult horses with no evidence of ophthalmic disease. Methods: Horses were randomly assigned to a control group and 2 treatment groups of equal sizes (n = 5). Horses assigned to the treatment groups received an NSAID (flunixin meglumine, 1.1 mg/kg PO q24h or firocoxib, 0.1 mg/kg PO q24h for 7 days). Horses in the control group received no medications. Concentrations of flunixin meglumine and firocoxib in serum and aqueous humor and prostaglandin (PG) E₂ in aqueous humor were determined on days 1, 3, and 5 and aqueous : serum ratios were calculated. Results: Firocoxib penetrated the aqueous humor to a significantly greater extent than did flunixin meglumine at days 3 and 5. Aqueous : serum ratios were 3.59 ± 3.32 and 11.99 ± 4.62% for flunixin meglumine and firocoxib, respectively. Ocular PGE₂ concentrations showed no differences at any time point among study groups. Conclusions and Clinical Importance: Both flunixin meglumine and firocoxib penetrated into the aqueous humor of horses. This study suggests that orally administered firocoxib penetrates the aqueous humor better than orally administered flunixin meglumine at label dosages in the absence of ocular inflammation. Firocoxib should be considered for the treatment of inflammatory ophthalmic lesions in horses at risk for the development of adverse effects associated with nonselective NSAID administration.     

Using the indicator amino acid oxidation technique to study threonine requirements in horses receiving a predominantly forage diet

Threonine has been reported to be the second limiting amino acid in typical equine diets, but its actual requirement has not been determined in horses. To evaluate amino acid metabolism and requirements, the indicator amino acid oxidation (IAAO) method has been successfully used in other species. The objective of this research was to estimate threonine requirements in mature horses fed timothy hay and concentrate in 4:1 ratio using the IAAO method. Six Thoroughbred mares (579.9 ± 46.7 kg) received each of 6 levels of threonine intake, 41, 51, 61, 70, 80 and 89 mg/kg BW/day, in a randomly determined order. Each study period was 7‐day long, and on day 6, blood samples were collected before and 90 min after feeding to measure amino acid concentrations using HPLC. On day 7, horses underwent IAAO procedures, which included a 2‐hr primed, constant intravenous infusion of [¹³C]sodium bicarbonate to measure total CO₂ production and a 4‐hr primed, constant oral administration of [1‐¹³C]phenylalanine to estimate phenylalanine oxidation to CO₂. Blood and breath samples were collected to measure blood [¹³C]phenylalanine, using GC‐MS analysis and breath ¹³CO₂ enrichment, using an infrared isotope analyser. Increasing threonine intake levels did not affect plasma phenylalanine oxidation by the ANOVA test (p > 0.05) but resulted in a linear decrease in phenylalanine oxidation (p = 0.04) without a breakpoint by the orthogonal linear contrast. This study is the first attempt to evaluate threonine requirements in horses by the IAAO method; however, threonine requirements are still unknown in mature horses at this time.     

Equine gastric ulcer syndrome in adult donkeys: Investigation on prevalence,anatomical distribution,and severity

The study was performed on 39 live donkeys that underwent gastroscopic examination. The lesions were recorded in accordance with the European College of Equine Internal Medicine Consensus Statement guidelines. The presence of Gasterophilus sp. larvae was also recorded. Larvae were collected and identified to species level. Fisher's exact test was used to compare different prevalence values for sex, age, and anatomical distribution of lesions. Gastric lesions were present in 20/39 (51.3% [35.6–67%]) donkeys; 19/39 (48.7% [95% confidence interval = 33–64.4%]) were affected only by equine squamous gastric disease (ESGD), while 1/39 (2.6% [0–7.5%]) showed both ESGD and equine glandular gastric disease (EGGD), thus 95% of positive donkeys showed lesions located in the nonglandular mucosa. The ESGD grade was 0/4 (48.7% [33–64.4%]) in 19/39, 1/4 (12.8% [2.3–23.3%]) in 5/39, 2/4 (25.6% [11.9–39.5%]) in 10/39, 3/4 in 4/39 (10.3% [0.7–19.8%]) and 4/4 in 1/39 (2.6% [0–7.5%]) donkeys, respectively. The EGGD lesion was a mild depression in the ventral glandular fundus. ESGD was primary in all the donkeys included and lesions were located around the cardia and along the lesser curvature. Gasterophilus sp. larvae were present in all animals and were identified as third‐stage larvae of Gasterophilus intestinalis. No animals showed clinical signs of equine gastric ulcer syndrome (EGUS). No significant differences relating to sex, age or breed were found in the prevalence of EGUS in this study, while the proportion of donkeys affected by ESGD was statistically higher than those affected by EGGD. To the best of our knowledge, this is the first report on the gastroscopic evaluation of EGUS in live donkeys. Our results show a higher prevalence of EGUS in live donkeys than values previously reported by other authors in donkeys that were dead or had been subjected to euthanasia. The detection of third‐stage G. intestinalis larvae was not unexpected since these can be found in the stomach of equids throughout the year, and G. intestinalis has been reported as the most common Gasterophilus sp. in Italy.     

Effects of supplements containing turmeric and devil’s claw on equine gastric ulcer scores and gastric juice pH

Supplements containing turmeric (Curcuma longa) and devil’s claw (Harpagophytum species) are commonly fed to horses to decrease inflammation and pain, but because these supplements contain spices and plant irritants, warning labels such as 'these supplements might cause gastric irritation' are required. The purpose of this study was to determine whether supplements containing turmeric and devil’s claw cause or worsen gastric ulcers in stall-confined horses, as suggested in required cautions that appear on the labels of these animal products. Twelve clinically healthy Thoroughbred horses with naturally occurring equine gastric ulcer syndrome (EGUS) scores >0 were included in a noncrossover study design. Horses were stratified by EGUS score and assigned to either the treatment (supplements containing turmeric and devil’s claw) or control (same supplements without active ingredients) group and fed the supplements for 28 days. Gastroscopy was performed on Days 0, 14 and 28. The EGUS score, nonglandular ulcer number (NGN) and severity (NGS) scores, and glandular number (GN) and severity (GS) scores were recorded during each gastroscopy by a masked investigator (F.M.A.). In addition, bodyweight, gastric juice pH, packed cell volume (PCV), total protein (TP) and blood biochemical results were measured on Day 0 and Day 28. Mean EGUS and NGS scores were significantly lower in both treatment and control groups by Days 14 and 28, when compared to Day 0. NGN score was not different among groups. Bodyweight, gastric juice pH and blood parameters did not change during the study. In conclusion, supplements containing turmeric and devil’s claw did not cause or worsen gastric ulcers or alter health parameters after 28 days of feeding.     

Influence of an n‐3 long‐chain polyunsaturated fatty acid‐enriched diet on experimentally induced synovitis in horses

Dietary n‐3 long‐chain polyunsaturated fatty acid (LCPUFA) supplementation has previously been shown to modify joint‐related inflammation in several species, although information in the horse is lacking. We investigated whether dietary supplementation with n‐3 LCPUFA would modify experimentally induced synovitis in horses. Twelve, skeletally mature, non‐pregnant mares were randomly assigned to either a control diet (CONT) or an n‐3 long‐chain fatty acid‐enriched treatment diet (N3FA) containing 40 g/day of n‐3 LCPUFA for 91 days. Blood samples taken on days 0, 30, 60 and 90, and synovial fluid collected on days 0 and 90 were processed for lipid composition. On day 91, joint inflammation was stimulated using an intra‐articular (IA) injection of 100 ng of recombinant equine IL‐1beta (reIL‐1β). Synovial fluid samples taken at post‐injection hours (PIH) 0, 4, 8 and 24 were analysed for prostaglandin E₂ (PGE₂), matrix metalloproteinase (MMP) activity and routine cytology. Synovium and articular cartilage samples collected at PIH 8 were analysed for gene expression of MMP 1 and MMP 13, interleukin‐1beta (IL‐1β), cyclooxygenase 2 (COX‐2), tumour necrosis factor‐alpha and the aggrecanases, a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)‐4 and ADAMTS‐5. A 90‐day feeding period of n‐3 LCPUFA increased serum phospholipid and synovial fluid lipid compositions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) compared to CONT horses. The reIL‐1β injection caused an inflammatory response; however, there was no effect of dietary treatment on synovial fluid PGE2 content and MMP activity. Synovial tissue collected from N3FA horses exhibited lower expression of ADAMTS‐4 compared to CONT horses. Despite the presence of EPA and DHA in the synovial fluid of N3FA horses, dietary n‐3 LCPUFA supplementation did not modify synovial fluid biomarkers compared to CONT horses; however, the lower ADAMTS‐4 mRNA expression in N3FA synovium warrants further investigation of n‐3 LCPUFA as a joint therapy.     

Lessons learned from a strangles outbreak on a large Standardbred farm

Streptococcus equi subspecies (ssp.) equi infection (strangles) remains one of the most frequently diagnosed and costly infectious diseases of horses. Large breeding herds, where a disease outbreak competes for personnel and financial resources needed for foaling management, present a special challenge for equine practitioners. A 15‐month outbreak involving 62 clinical cases of strangles occurred on a large Standardbred breeding farm (average population of 1400 horses). Sixteen asymptomatic horses were found to be PCR (polymerase chain reaction)‐positive for S. equi ssp. equi. During the outbreak, serological samples from 48 clinically normal horses were found to be seropositive for S. equi ssp. equi, confirming herd‐wide exposure. After several clinical cases of strangles had been diagnosed, an intranasal S. equi ssp. equi vaccine was administered to clinically normal horses (n = 558) considered to be at risk of exposure. Strangles complications included 7 fatalities (none in vaccinated horses) and 6 cases of purpura haemorrhagica (4 in vaccinated horses). Midway through the outbreak, injectable, sustained release ceftiofur crystalline free acid (CCFA), given as an initial dose followed by a second dose 4 days later, was used exclusively for systemic antimicrobial treatment of clinically affected and PCR‐positive horses. This antimicrobial regimen coincided with a reduction in disease incidence and eventual resolution of the outbreak. Two horses with persistent guttural pouch infection were endoscopically confirmed as carrier horses. The herd history demonstrated that a strangles outbreak will often result in asymptomatic carrier horses and that identification and treatment of these horses are necessary to eliminate long‐term sources of infection. Ceftiofur crystalline free acid was found to be a suitable antimicrobial due to its activity against S. equi ssp. equi and the efficiencies associated with twice parenteral dosing during a 10‐day treatment period. Occurrence of purpura in 4 vaccinated horses suggests that vaccination should be reserved for healthy seronegative horses and avoided during an active outbreak.     

Exploring relationships between body condition score,body fat,activity level and inflammatory biomarkers

Obesity is associated with inflammatory disorders in humans, including degenerative joint disease. While obesity is endemic in horses, its relationship to equine degenerative joint disease has not been explored. The current study sought to describe relationships between: body weight (BW), body condition score (BCS), lameness grade (AAEP), total body fat mass (kg; FM) and fat per cent (FP) [multifrequency bioelectrical impedance analysis (mfBIA)], age, gender, activity level (AL), synovial fluid (SF) and plasma (PL) PGE₂ and glycosaminoglycan (GAG) in horses. During this field investigation, the BCS (of nine) of 54 horses at multiple farms in southern Ontario, Canada, was determined. Horses were categorized as thin (BCS=3/9; n = 6), moderate (BCS=4 or 5/9; n = 18), overweight (BCS=6 or 7/9; n = 19) or obese (BCS=8 or 9/9; n = 11). Total fat mass (kg) and body fat% was measured using mfBIA, lameness was assessed (AAEP lameness scale) and synovial fluid was collected via aseptic arthrocentesis from the left intercarpal joint for assessment of inflammatory biomarkers (PGE₂, GAG). Means were compared with a one‐way ANOVA; correlation coefficients were calculated using a Spearman Rank Order Correlation to reveal correlations between variables. BCS was positively correlated with BW, FM, FP, AL and PL‐PGE₂. BW was also significantly positively correlated with PL‐PGE₂. It is concluded that BCS is significantly correlated with PL‐PGE₂, due in part to the combined effect of AL and body condition. Net inflammatory effects of body fat on risk for joint disease require further study.     

Effects of phenylbutazone alone or in combination with flunixin meglumine on blood protein concentrations in horses

OBJECTIVE: To assess effects of treatment with phenylbutazone (PBZ) or a combination of PBZ and flunixin meglumine in horses. ANIMALS: 24 adult horses. PROCEDURE: 13 horses received nonsteroidal antiinflammatory drugs (NSAIDs) in a crossover design. Eleven control horses were exposed to similar environmental conditions. Treated horses received PBZ (2.2 mg/kg, PO, q 12 h, for 5 days) and a combination of PBZ and flunixin meglumine (PBZ, 2.2 mg/kg, PO, q 12 h, for 5 days; flunixin meglumine, 1.1 mg/kg, IV, q 12 h, for 5 days). Serum samples were obtained on day 0 (first day of treatment) and day 5, and total protein, albumin, and globulin were measured. RESULTS: 1 horse was euthanatized with severe hypoproteinemia, hypoalbuminemia, and colitis during the combination treatment. Comparisons revealed no significant difference between control horses and horses treated with PBZ alone. There was a significant difference between control and treated horses when administered a combination of PBZ and flunixin meglumine. Correction for horses with values >2 SDs from the mean revealed a significant difference between control horses and horses administered the combination treatment, between control horses and horses administered PBZ alone, and between horses receiving the combination treatment and PBZ alone. Gastroscopy of 4 horses revealed substantial gastric ulcers when receiving the combination NSAID treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of results of the study indicates the need for caution when administering a combination NSAID treatment to horses because the detrimental effects may outweigh any potential benefits.     

Comparison of efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis

OBJECTIVE: To compare efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis. DESIGN: Randomized controlled clinical trial. ANIMALS: 253 client-owned horses with naturally occurring osteoarthritis. PROCEDURES: Horses were treated with firocoxib (0.1 mg/kg [0.045 mg/lb], PO, q 24 h) or phenylbutazone (4.4 mg/kg [2 mg/lb], PO, q 24 h) for 14 days. Physical examinations and lameness evaluations were performed prior to treatment and after 7 and 14 days. Clinical improvement was defined as a reduction of at least 1 lameness grade or a combined reduction of at least 3 points in scores for pain during manipulation or palpation, joint swelling, joint circumference, and range of motion. RESULTS: Proportion of horses clinically improved on day 14 for the firocoxib group (104/123 [84.6%]) was not significantly different from the proportion for the phenylbutazone group (103/119 [86.6%]). Proportion of horses that were improved on day 14 was significantly greater for horses treated with firocoxib than for horses treated with phenylbutazone with regard to score for pain on manipulation or palpation (P = 0.028), joint circumference score (P = 0.026), and range of motion score (P = 0.012), but not for overall lameness score or joint swelling score. No direct treatment-related adverse effects were detected during the study. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that overall clinical efficacy of a paste formulation of firocoxib in horses with naturally occurring osteoarthritis was comparable to efficacy of a paste formulation of phenylbutazone.     

Pharmacokinetics,disposition, and plasma concentrations of dimethyl sulfoxide (DMSO) in the horse following topical,oral, and intravenous administration

Compartmental models were used to investigate the pharmacokinetics of intravenous (i.v. ), oral (p.o. ), and topical (TOP ) administration of dimethyl sulfoxide (DMSO ). The plasma concentration–time curve following a 15‐min i.v. infusion of DMSO was described by a two‐compartment model. Median and range of alpha (t _1/2α) and beta (t _1/2β) half‐lives were 0.029 (0.026–0.093) and 14.1 (6.6–16.4) hr, respectively. Plasma concentration–time curves of DMSO following p.o. and TOP administration were best described by one‐compartment absorption and elimination models. Following the p.o. administration, median absorption (t _1/2ab) and elimination (t _1/2e) half‐lives were 0.15 (0.01–0.77) and 15.5 (8.5–25.2) hr, respectively. The plasma concentrations of DMSO were 47.4–129.9 μg/ml, occurring between 15 min and 4 hr. The fractional absorption (F ) during a 24‐hr period was 47.4 (22.7–98.1)%. Following TOP administrations, the median t _1/2ab and t _1/2e were 1.2 (0.49–2.3) and 4.5 (2.1–11.0) hr, respectively. Plasma concentrations were 1.2–8.2 μg/ml occurring at 2–4 hr. Fractional absorption following TOP administration was 0.48 (0.315–4.4)% of the dose administered. Clearance (Cl) of DMSO following the i.v. administration was 3.2 (2.2–6.7) ml hr^?1 kg^?1. The corrected clearances (Cl_F ) for p.o. and TOP administrations were 2.9 (1.1–5.5) and 4.5 (0.52–18.2) ml hr^?1 kg^?1.     

Pathology of gastritis and gastric ulceration in the horse. Part 2: A scoring system

Reasons for performing study: High numbers of racehorses in training are reported to have gastric ulceration. Gross lesion scoring systems exist, but there is no fixed protocol with which to record gastric microscopic findings. In man, the histological classification of stomach lesions helps in the identification of recognised and emerging aetiologies of gastric disease and aids accurate comparison of findings between studies. In horses, the development of such a system would therefore be of benefit. Objectives: To develop a pathological scoring system that can be applied to examine samples of the equine stomach at biopsy and post mortem. Methods and results: The equine gastritis grading (EGG) system was developed initially using horse stomachs at post mortem. The protocol involved sampling tissue from 5 fixed locations within the squamous and glandular regions. Histological examination recorded both type and degree of inflammatory infiltrate and the presence of erosions, ulceration or any other reactive change in each slide. These results were combined and an overall diagnosis of gastritis type given for each stomach. Conclusions and potential relevance: This is the first example of a complete pathological scoring system developed specifically for recording gastric lesions in the horse. It provides a thorough and repeatable method with which to examine the equine stomach in microscopic detail. It can be used in diagnostic or research situations and the consistency of the information gathered will enable accurate comparison of data between different studies. It aims to give an indication as to the currently undetermined pathological variations seen in the stomach of healthy and diseased horses, as well as increasing the understanding of the pathogenesis of gastritis and gastric ulceration. Using this information, interpretation of biopsy samples is improved.     

Re‐evaluation of the regulation of omeprazole in racehorses: An evidence‐based approach

Medication control and doping control have been established in horse racing to ensure the integrity of the sport and the welfare of the horses. This ensures that horses do not compete under the influence of any drugs, including omeprazole, a therapeutic medication used to treat equine gastric ulcer syndrome. In this study, pharmacokinetic data were produced in equine plasma and urine following an oral administration of 4 mg/kg of generic buffered formulation of omeprazole to six Thoroughbred horses in five daily doses to determine an appropriate screening limit and detection time in equine plasma and to assess whether the current detection time of 72 hr in equine urine would be applicable when an alternative omeprazole product is administered. C _max of 436–2,432 ng/ml and AUC _0–tau of 1,476–4,371 ng hr ml^?1 were obtained for plasma and indicated, in conjunction with other published oral omeprazole studies, that an appropriate plasma screening limit would be 500 pg/ml with a detection time of 48 hr. Urine analysis showed that omeprazole could be detected for up to 25 hr above the previously established urine screening limit of 500 pg/ml and thus indicated that the detection time advice could be potentially reduced from 72 to 48 hr to allow more comprehensive treatment of gastric lesions.     

Effects of clopidogrel and aspirin on platelet aggregation, thromboxane production, and serotonin secretion in horses

Background: Critically ill horses are susceptible to thrombotic disease, which might be related to increased platelet reactivity and activation. Objectives: To compare the effect of oral clopidogrel and aspirin (ASA) on equine platelet function. Animals: Six healthy adult horses. Methods: Horses received clopidogrel (2 mg/kg PO q24h) or ASA (5 mg/kg PO q24h) for 5 days in a prospective randomized cross‐over design. Platelet aggregation responses to adenosine diphosphate (ADP) and collagen via optical aggregometry, and platelet secretion of serotonin (5HT) and production of thromboxane B₂ (TXB₂) by ELISA were evaluated. In horses receiving clopidogrel, high‐performance liquid chromatography analysis for clopidogrel and its carboxylic‐acid metabolite SR 26334 was performed. Results: SR 26334 was identified in all clopidogrel‐treated horses, although the parent compound was not detected. Clopidogrel resulted in decreases in ADP‐induced platelet aggregation persisting for 120 hours after the final dose. ADP‐induced platelet aggregation decreased from a baseline of 70.2 ± 14.7% to a minimum of 15.9 ± 7.7% 24 hours after the final dose (P < .001). Collagen‐induced aggregation decreased from a baseline of 93 ± 9.5% to a minimum of 70.8 ± 16.9% 48 hours after the final dose (P < .001). ASA did not decrease platelet aggregation with either agonist. ASA decreased serum TXB₂ from a baseline value of 1310 ± 1045 to 128 ± 64 pg/mL within 24 hours (P < .01). Conclusions and Clinical Importance: Clopidogrel effectively decreases ADP‐induced platelet aggregation in horses, and could have therapeutic applications for equine diseases associated with platelet activation.     

Effects of intravenously administered esomeprazole sodium on gastric juice pH in adult female horses

Background: Gastric ulcers are common in horses and treatment of horses that cannot be administered oral medication can be problematic. Objectives: To evaluate the efficacy of esomeprazole sodium administered intravenously on gastric juice pH and gastric ulcer scores in horses. Animals: Twelve adult female Quarter Horses. Methods: Esomeprazole sodium (0.5 mg/kg IV) was administered once daily to 8 horses (treatment group) and saline (5 mL IV) was administered to 4 horses (control group) for 13 consecutive days. Gastroscopy was performed and gastric juice pH and gastric ulcer score were recorded before and 1 hour after the administration of esomeprazole sodium or saline on days 1 and 5, then on day 14, 23 hours after the 13th daily dose of esomeprazole sodium or saline. Results: When compared with values before treatment, gastric juice pH was higher in esomeprazole sodium‐treated horses after treatment (4.25 ± 2.39 versus 6.43 ± 1.18; P= .002). Also, gastric juice pH was higher (P= .001) in esomeprazole sodium‐treated horses compared with saline‐treated control horses on day 5 and on day 14 values. Gastric ulcers were seen in 5/12 (43%) horses in the study. Conclusions and Clinical Importance: Esomeprazole sodium shows promise for treatment of gastric ulcers in horses with signs of dysphagia, gastric reflux, or other conditions that restrict oral intake of the current Federal Drug Administration‐approved omeprazole paste.     

Evaluation of the oral antimitotic agent (ABT-751) in dogs with lymphoma

Background

ABT‐751 is a novel orally available antimitotic agent that targets microtubule polymerization. This mechanism may suggest potential activity in canine lymphoma.

Objective

Determine a maximum tolerated dose for ABT‐751, and assess long‐term tolerability and activity in canine lymphoma.

Animals

Thirty dogs with newly diagnosed (n = 19) or relapsed (n = 11) non‐Hodgkin's lymphoma.

Methods

Dogs (n = 11) were enrolled in a rapid dose escalation study to define the maximum tolerated dose. Upon definition of a maximally tolerated dose, a cohort expansion of 19 dogs allowed verification of long‐term tolerability and assessment of activity. Study endpoints in the cohort expansion included chronic tolerability, response rate, response duration, and time to progression. Additional endpoints included serum pharmacokinetics, lymph node drug concentrations, and changes in circulating endothelial cells.

Results

The maximum tolerated dose of ABT‐751 was 350 mg/m² PO q24h. Dose‐limiting toxicities included vomiting and diarrhea, which resolved with a schedule adjustment to 350 mg/m² PO q48h. ABT‐751 was consistently detected in lymphoma tissue samples from dogs treated at or above the maximum tolerated dose. In the cohort expansion, objective responses were seen in 3/15 (20%) dogs with a response duration ranging from 21 to 111 days. Decreases in circulating endothelial cells were seen in 10 dogs at day 7 (2 responding dogs and 8 nonresponding dogs).

Conclusion

ABT‐751 was well tolerated at 350   mg/m² PO q24h for 7 days and then q48h thereafter. Activity of ABT‐751 suggested a rationale for additional studies of ABT‐751 as part of a combination chemotherapy protocol for lymphoma or other canine cancers.     

Evaluation of gastric pressures as an indirect method for measurement of intraabdominal pressures in the horse

Objective – To develop an indirect method for measurement of intraabdominal pressures in the standing horse using measurement of gastric pressures as a less invasive technique, and to compare this method with direct intraabdominal pressures obtained from the peritoneal cavity. Design – Prospective, experimental study. Setting – University‐based equine research facility. Animals – Ten healthy adult horses, 7 geldings and 3 mares. Interventions – Gastric pressures were measured using a nasogastric tube with a U‐tube manometry technique, while intraperitoneal pressures were measured with a peritoneal cannula. Measurements of intraabdominal pressure were obtained by both methods, simultaneously, and were evaluated using 5 increasing volumes of fluid infused into the stomach (0, 400, 1,000, 2,000, and 3,000 mL). Bias and agreement between the 2 methods were determined using Bland‐Altman analysis and Lin's concordance correlation coefficients. Measurements and Main Results – Mean gastric pressure was 14.44±4.69 cm H₂O and ranged from 0 to 25.8 cm H₂O. Intraperitoneal pressure measurements were generally subatmospheric, and ranged from ?6.6 to 3.1 cm H₂O (mean±SD, ?1.59±2.09 cm H₂O). Measurements of intraperitoneal pressures were repeatable; however, intra‐ and interindividual variance was significantly larger for measurements of gastric pressures. The mean and relative bias for comparison between the 2 techniques was 15.9±5.3 cm H₂O and 244.3±199.2%, respectively. The Lin's concordance correlation coefficient between gastric and intraperitoneal pressures was ?0.003 but this was not statistically significant (P=0.75). Conclusions – There was no statistical concordance between measurements of intraabdominal pressure using gastric and intraperitoneal pressure measurement, indicating that gastric pressures cannot be substituted for intraperitoneal pressure measurement. Direct measurement of intraperitoneal pressures may be a more consistent method for comparison of intraabdominal pressures between horses, due to less variability within and between individuals.     

Pharmacokinetics of chloramphenicol base in horses and comparison to compounded formulations

Chloramphenicol is commonly used in horses; however, there are no studies evaluating the pharmacokinetics of veterinary canine‐approved tablets. Studies using different formulations and earlier analytical techniques led to concerns over low bioavailability in horses. Safety concerns about human health have led many veterinarians to prescribe compounded formulations that are already in suspension or paste form. The objective of this study was to evaluate the pharmacokinetics of approved chloramphenicol tablets in horses, along with compounded preparations. The hypothesis was that chloramphenicol has low absorption and a short half‐life in horses leading to low serum concentrations and that compounded preparations have lower relative bioavailability. Seven horses were administered chloramphenicol tablets (50 mg/kg orally). In a crossover design, they were administered two compounded preparations to compare all three formulations at the same dose (50 mg/kg). C_max was 5.25 ± 4.07 μg/ml at 4.89 hr, 4.96 ± 3.31 μg/ml at 4.14 hr, and 3.84 ± 2.96 μg/ml at 4.39 hr for the tablets, paste, and suspension, respectively. Elimination half‐life was 2.65 ± 0.75, 3.47 ± 1.47, and 4.36 ± 4.54 hr for tablets, paste, and suspension, respectively. The AUC_0→∞ was 17.93 ± 7.69, 16.25 ± 1.85, and 14.00 ± 5.47 hr*μg/ml for the tablets, compounded paste, and compounded suspension, respectively. Relative bioavailability of compounded suspension and paste was 78.1% and 90.6%. C_max after administration of all formulations did not reach the recommended MIC target of 8 μg/ml set by the Clinical Laboratory Standards Institute (CLSI) for most bacteria. Multidose studies are warranted, but the low serum concentrations suggest that bacteria with MIC values lower than CLSI recommendations should be targeted in adult horses.     

The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses

Davis, J. L., Marshall, J. F., Papich, M. G., Blikslager, A. T., Campbell, N. B. The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses. J. vet. Pharmacol. Therap. 34 , 12–16. The purpose of this study was to determine the pharmacokinetics of deracoxib following oral administration to horses. In addition, in vitro equine whole blood cyclooxygenase (COX) selectivity assays were performed. Six healthy adult horses were administered deracoxib (2 mg/kg) orally. Plasma samples were collected prior to drug administration (time 0), and 10, 20, 40 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after administration for analysis with high pressure liquid chromatography using ultraviolet detection. Following PO administration, deracoxib had a long elimination half‐life (t_1/2k₁₀) of 12.49 ± 1.84 h. The average maximum plasma concentration (C_max) was 0.54 μg/mL, and was reached at 6.33 ± 3.44 h. Bioavailability was not determined because of the lack of an IV formulation. Results of in vitro COX selectivity assays showed that deracoxib was selective for COX‐2 with a COX‐1/COX‐2 ratio of 25.67 and 22.06 for the IC₅₀ and IC₈₀, respectively. Dosing simulations showed that concentrations above the IC₈₀ for COX‐2 would be maintained following 2 mg/kg PO q12h, and above the IC₅₀ following 2 mg/kg PO q24h. This study showed that deracoxib is absorbed in the horse after oral administration, and may offer a useful alternative for anti‐inflammatory treatment of various conditions in the horse.