Pharmacokinetics of methocarbamol and phenylbutazone in exercised Thoroughbred horses

Methocarbamol (MCBL) is commonly used in performance horses for the treatment of skeletal muscle disorders. Current regulatory recommendations for show horses and racehorses are based on a single oral dose of 5 g, although doses in excess of this are often administered. The goal of the current study was to characterize the disposition of MCBL following higher dose administration and administration in combination with another commonly used drug in performance horses, phenylbutazone (PBZ). Exercised Thoroughbred horses were administered various doses of MCBL as a sole agent and MCBL in combination with PBZ. Blood samples were collected at various times, concentrations of MCBL and PBZ measured using LC‐MS/MS and pharmacokinetic parameters calculated using compartmental analysis. Following administration of 15 g of MCBL, either as part of a single‐ or multiple‐dose regimen, a number of horses exceeded the Association of Racing Commissioners International and the United States Equestrian Federation's recommended regulatory threshold at the recommended withdrawal time. There was not a significant difference between horses that received only MCBL and those that received MCBL and PBZ. Results of the current study support an extended withdrawal guideline when doses in excess of 5 g are administered.     

Idiopathic haemarthrosis in eight horses

Objectives To review eight horses diagnosed with idiopathic haemarthrosis and to describe the intra‐articular use of yttrium‐90 (⁹⁰Y) and methylprednisolone acetate (MPA) in recurrent haemarthrosis cases. Design Retrospective case series. Method The medical records, diagnostic images, histopathology and outcome of all horses diagnosed with idiopathic haemarthrosis between 1998 and 2010 were reviewed. Results Four Thoroughbred racehorses with haemarthrosis of the antebrachiocarpal joint had severe acute lameness (median, grade 4) and marked joint effusion after high‐speed exercise. Another four horses (2 Thoroughbred racehorses, 1 Standardbred racehorse, 1 Warmblood) had haemarthrosis of the tarsocrural joint and presented with mild, intermittent lameness (median, grade 1) and marked, persistent joint effusion. Six of the eight horses had recurrent haemarthrosis prior to treatment. Radiographic and nuclear scintigraphic examinations did not identify bone pathology. Diagnostic arthroscopy (7 cases) identified grossly hypertrophied yellow/brown discoloured synovium. Synovial histopathology of these cases revealed chronic synovial hyperplasia with severe haemosiderosis and granulomatous inflammatory reaction of varying severity. All horses underwent rest, bandaging and phenylbutazone administration. Two horses had subtotal mechanical synovectomy, four horses had intra‐articular administration of ⁹⁰Y and MPA, and one horse underwent both treatments. Seven cases returned to their previous use (median time, 7 months). Haemarthrosis recurred in three horses, two of which had received the ⁹⁰Y and MPA treatment. Conclusion Idiopathic haemarthrosis should be considered a differential for acute and recurrent joint related lameness and effusion. Recurrence appears not uncommon and the use of intra‐articular ⁹⁰Y and MPA in conjunction with a conservative management treatment protocol warrants further evaluation.     

Pharmacokinetics of low-dose methotrexate in horses

This study aimed to investigate both the pharmacokinetic behavior and tolerance of methotrexate (MTX) in horses to design a specific dosing regimen as a new immunomodulatory drug for long-term treatment. To determine the primary plasma pharmacokinetic variables after single intravenous, subcutaneous or oral administration, six horses were administered 0.3 mg/kg MTX in a crossover design study. After a 10-week washout, MTX was administered subcutaneously to three of the six previously treated horses at a dose of 0.3 mg/kg once per week for 3 months. In both studies, MTX and metabolite concentrations were measured using LC-MS/MS. The absolute bioavailability of MTX was 73% following subcutaneous administration but less than 1% following oral administration. The plasma clearance was 1.54 ml min⁻¹ kg⁻¹ (extraction ratio = 2%). After 24 hr, plasma concentrations were below the LOQ. No adverse effects were noted except for a moderate reversible elevation in liver enzymes (GLDH). With regards to the main metabolites of MTX, very low concentrations of 7-hydroxy-MTX were found, whereas polyglutamated forms (mainly short chains) were found in red blood cells. A subcutaneous dose of 0.2 mg kg⁻¹ week⁻¹ may be safe and relevant in horses, although this has yet to be clinically confirmed.     

Evaluation of the diffusion of corticosteroids between the distal interphalangeal joint and navicular bursa in horses

OBJECTIVE: To determine whether clinically effective concentrations of methylprednisolone or triamcinolone can be achieved in the navicular bursa after injection of methylprednisolone acetate (MPA) or triamcinolone acetonide (TA) into the distal interphalangeal joint (DIPJ) and whether clinically effective concentrations of these drugs can be achieved in the DIPJ after injecting the navicular bursa with the same doses of MPA or TA. ANIMALS: 32 healthy horses. PROCEDURES: Horses in groups 1 through 4 received 40 mg of MPA in the DIPJ, 10 mg of TA in the DIPJ, 40 mg of MPA in the navicular bursa, and 10 mg of TA in the navicular bursa, respectively. Concentrations of corticosteroids that diffused into the adjacent synovial structure were determined. RESULTS: For group 1, injection of MPA into the DIPJ yielded a mean +/- SD concentration of 0.24 +/- 0.072 microg of methylprednisolone/mL in the navicular bursa. For group 2, injection of TA into the DIPJ yielded 0.124 +/- 0.075 microg of triamcinolone/mL in the navicular bursa. For group 3, injection of MPA into the navicular bursa yielded 0.05 +/- 0.012 microg of methylprednisolone/mL in the DIPJ. For group 4, injection of TA into the navicular bursa yielded 0.091 +/- 0.026 microg of triamcinolone/mL in the DIPJ. CONCLUSIONS AND CLINICAL RELEVANCE: A clinically effective concentration of methylprednisolone or triamcinolone diffused between the DIPJ and navicular bursa after intra-articular or intrabursal injection, which would justify injection of the DIPJ with MPA or TA to ameliorate inflammation of the navicular bursa.     

Synovial and serum levels of triamcinolone following intra-articular administration of triamcinolone acetonide in the horse.

Seven mature thoroughbred horses, weighing between 400 and 541 kg, were each injected intra-articularly into three joints with 6 mg/joint of triamcinolone acetonide (Vetalog). The fourth joint, the control, was injected with saline. Synovial fluid was taken from all four legs of the horses on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following the injections. Triamcinolone acetonide was assayed by a radioimmunoassay. Blood was collected at 1, 2, 4, 6, 12 h and on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following injection of either triamcinolone or saline. Both cortisol and triamcinolone were assayed. The results show that the synovial fluid level of triamcinolone was 7.5 micrograms/ml 1 day following treatment and decreased to 10 ng/ml by the 4th day. These low levels were maintained for approximately 14 days. By the 15th day, the triamcinolone was below a detectable level. Serum levels of triamcinolone increased to 3 ng/ml within 1 h and further increased to a peak of 4.3 ng/ml at 4th h. The level then decreased to 2 ng/ml at 24 h and to nearly an undetectable level in 48 h. The mean level of serum cortisol, on the other hand, gradually decreased as the serum level of triamcinolone increased. As the serum level of triamcinolone reached an undetectable level on the 2nd day, the serum cortisol level gradually increased and returned to the pre-administration level by the 5th day. These results showed that the intra-articular administration of triamcinolone maintained triamcinolone in the synovial fluid for 4-14 days and that the triamcinolone reached the blood within 1 h. The serum level of triamcinolone was maintained for 2 days and resulted in the inhibition of adrenal function for 4 days.     

Evaluation of plasma concentration after intravenous and intramuscular penicillin administration over 24 hr in healthy adult horses

Penicillin is administered intravenously (IV) or intramuscularly (IM) to horses for the prevention and treatment of infections, and both routes have disadvantages. To minimize these shortcomings, a 24‐hr hybrid administration protocol (HPP) was developed. Our objective was to determine penicillin plasma concentrations in horses administered via HPP. Venous blood was collected from seven healthy horses administered IV potassium penicillin G at 0 and 6 hr and IM procaine penicillin G at 12 hr. Blood was collected at 2‐hr intervals from 0 to 20 hr and at 24 hr. Plasma penicillin concentrations were measured using liquid chromatography and mass spectrometry. Penicillin susceptibility from equine isolates was examined to determine pharmacodynamic targets. The MIC₉₀ of penicillin for 264 isolates of Streptococcus sp. was ≤0.06 μg/ml. For the 24‐hr dosing interval, the mean plasma penicillin concentration was >0.07 μg/ml. Five horses (72%) exceeded 0.06 μg/ml for 98% of the dosing interval, and two horses exceeded this value for 52%–65% of the dosing interval. The HPP achieved mean plasma penicillin concentrations in healthy adult horses above 0.07 μg/ml for a 24‐hr dosing interval. However, individual variations in plasma concentrations were apparent and deserve future clinical study.     

Current joint therapy usage in equine practice: a survey of veterinarians 2009

Reasons for performing study: Medications are frequently employed to treat intra‐articular (IA) problems in the performance horse. Actual usage of the different IA medications in horses is not available. Objectives: To determine the most common usage of these medications, members of the American Association of Equine Practitioners (AAEP) were surveyed. Methods: An email link to an online survey was electronically sent to 6305 AAEP members and the responses tabulated and analysed with a logistic regression model. Results: A total of 831 survey responses were submitted and tabulated. Eighty per cent of the respondents indicated that they see 100% equine cases in their practice. The majority of respondents (77%) use triamcinolone acetonide (TA) to treat high motion joints and 73% use methylprednisolone acetate (MPA) to treat low motion joints. Veterinarians treating the Western performance and Sport horse were significantly more likely to use TA in high motion joints compared to MPA (P = 0.0201 and P<0.0001, respectively). Triamcinolone acetonide use compared to MPA in high motion joints by racehorse veterinarians was significantly lower compared to other veterinarians (P<0.0001). Polysulphated glycosaminoglycan (Adequan) and hyaluronate sodium (Legend) were the most commonly used disease modifying products (63 and 57% of respondents, respectively). Sport horse practitioners were significantly more likely than race or show horse veterinarians to utilise IRAP products (P = 0.0035 and P = 0.04, respectively). Respondents who had been in practice for more than 10 years were significantly less likely to use antimicrobials in their joint injections compared to those in practice for less than 10 years (P<0.0001). Conclusions: Significant differences existed in usage of medications related to primary discipline treated and years practicing. Potential relevance: The results of this study aid in defining the current usage of different joint therapy medications within equine practice. This knowledge can guide further research as well as education.     

Pharmacokinetics and effects on thromboxane B2 production following intravenous administration of flunixin meglumine to exercised thoroughbred horses

Flunixin meglumine is commonly used in horses for the treatment of musculoskeletal injuries. The current ARCI threshold recommendation is 20 ng/mL when administered at least 24 h prior to race time. In light of samples exceeding the regulatory threshold at 24 h postadministration, the primary goal of the study reported here was to update the pharmacokinetics of flunixin following intravenous administration, utilizing a highly sensitive liquid chromatography–mass spectrometry (LC‐MS). An additional objective was to characterize the effects of flunixin on COX‐1 and COX‐2 inhibition when drug concentrations reached the recommended regulatory threshold. Sixteen exercised adult horses received a single intravenous dose of 1.1 mg/kg. Blood samples were collected up to 72 h postadministration and analyzed using LC‐MS. Blood samples were collected from 8 horses for determination of TxB₂ and PGE₂ concentrations prior to and up to 96 h postflunixin administration. Mean systemic clearance, steady‐state volume of distribution and terminal elimination half‐life was 0.767 ± 0.098 mL/min/kg, 0.137 ± 0.12 L/kg, and 4.8 ± 1.59 h, respectively. Four of the 16 horses had serum concentrations in excess of the current ARCI recommended regulatory threshold at 24 h postadministration. TxB₂ suppression was significant for up to 24 h postadministration.     

Comparison of efficacy and tolerability of isoflupredone and dexamethasone in the treatment of horses affected with recurrent airway obstruction ('heaves')

REASONS FOR PERFORMING STUDY: Corticosteroids are currently the most effective drugs for the control of 'heaves' in horses. However, there is limited information concerning the comparative efficacy and tolerability of the various corticosteroids when used for treatment. OBJECTIVES: To compare the therapeutic and side effects of isoflupredone acetate to those of dexamethasone. METHODS: A parallel design to compare the effects of 2 corticosteroids by evaluating lung function, serum cortisol and electrolyte concentrations, response to ACTH stimulation and haematology sequentially during a 14 day control period (no treatment), followed by 14 day treatment with either isoflupredone acetate (0.03 mg/kg i.m. s.i.d., n = 6) or dexamethasone (0.04 mg/kg i.v. s.i.d., n = 6) and 7 days of wash-out. RESULTS: Both drugs were well tolerated clinically and resulted in a significant improvement in lung function that started on Day 3 and lasted for the treatment and wash-out periods. Blood cortisol levels were significantly decreased during the treatment period in both groups of horses, but a normal response to ACTH stimulation was preserved. Serum electrolytes concentration of horses receiving dexamethasone was not affected by the treatment, but horses treated with isoflupredone demonstrated a significant decrease in serum potassium level. Both treatments induced stress changes in haematology. CONCLUSIONS AND POTENTIAL RELEVANCE: Isoflupredone is as effective as dexamethasone in the treatment of 'heaves'-affected horses but associated with hypokalaemia. Even if clinical signs of hypokalaemia were not observed, this is a side effect that deserves further investigation.     

Characteristics of Thoroughbred and Quarter Horse racehorses that sustained a complete scapular fracture

Reasons for performing study: To determine if scapular fractures occur in racehorses with distinctive characteristics. Objectives: To test the hypothesis that Thoroughbred (TB) and Quarter Horse (QH) racehorses with a scapular fracture have similar characteristics that are different from those of their respective racetrack populations. Methods: Necropsy findings, case details, last race information and career earnings for TB and QH racehorses that had a scapular fracture in California between 1990 and 2008 were retrospectively compared between breeds. Horse signalment, career earnings, career starts and race characteristics were obtained for all California racehorses. Comparisons were made between affected horses, other racehorses that died, and all horses that raced, in California during the 19 year period. Results: Seventy‐three TB and 28 QH racehorses had a similar, complete comminuted scapular fracture with an articular component, and right forelimb predilection. The QHs had a higher incidence of scapular fracture incurred during racing than TBs (0.98 vs. 0.39/1000 starters). The TB and QH incident rates for musculoskeletal deaths incurred racing were 20.5 and 17.5/1000 starters, respectively; however, a greater proportion of TB musculoskeletal deaths occurred training (40% vs. 8%). Horses with a scapular fracture were more likely to be male and aged 2 or ≥5 years than the racetrack population. Most affected QHs (64%) were 2‐year‐olds; most TBs (74%) were aged ≥3 years. Scapular fractures occurred more commonly during racing in QHs (70%) than TBs (44%). Race‐related scapular fracture was more likely to occur in a Maiden race than in a non‐Maiden race. Horses with a scapular fracture had fewer career starts than the racetrack population. Conclusions and potential relevance: Despite breed differences for signalment and exercise distances, both breeds incur a complete scapular fracture that is more likely to occur in the right scapula of young and older, male racehorses, early in their race career or after few races. Quarter Horses sustain a catastrophic scapular fracture more frequently than TBs.     

Pharmacokinetics of intra‐articular betamethasone sodium phosphate and betamethasone acetate and endogenous hydrocortisone suppression in exercising horses

To the date, no reports exist of the pharmacokinetics (PK) of betamethasone (BTM) sodium phosphate and betamethasone acetate administered intra‐articular (IA) into multiple joints in exercising horses. The purpose of the study was to determine the PK of BTM and HYD concentrations in plasma and urine after IA administration of a total of 30 mg BTM. Eight 4 years old Thoroughbred mares were exercised on a treadmill and BTM was administered IA. Plasma and urine BTM and HYD were determined via high performance liquid chromatography spectrometry for 6 weeks. Concentration‐time profiles of BTM and HYD in plasma and urine were used to generate PK estimates for non‐compartmental analyses and comparisons among times and HYD concentrations. BTM in plasma had greater T_max (T_max 0.8 h) vs. urine (T_max 7.1 h). Urine BTM concentration (ng/mL) and amount (AUC_last; h × ng/mL) were greater than plasma. HYD was suppressed for at least 3 days (<1 ng/mL) for all horses. The time of last quantifiable concentration of BTM (T_last; hour) was not significantly different in plasma than urine. Use of highly sensitive HPLC‐MS/MS assays enabled early detection and prolonged and consistent determination of BTM in plasma and urine.     

Equine duodenal motility,assessed by ultrasonography,as a predictor of reflux and survival following colic surgery

Intestinal dysmotility following equine colic surgery contributes negatively to financial and prognostic outcomes. This study assessed duodenal contractility as a predictor of post-operative reflux and survival to discharge in horses following colic surgery. Duodenal contractility was assessed using daily transabdominal ultrasound examinations in 49 horses for up to 7 days (Day 1 scan performed between 6 and 36 h post-surgery and sequential daily scans performed between 08.00 and 20.00 h) following colic surgery (September 2014–April 2017). The duodenum was visualised ventral to the right kidney, and duodenal contractions were measured over 2 min. The signalment of each horse and surgical findings were noted. Outcomes were defined as horses that refluxed (>5 L/24 h beyond 24 h) or did not reflux post-operatively and those that were survivors or were nonsurvivors. A significant difference in duodenal contractions at Day 1 post-operatively was identified between horses that refluxed (n = 8) and those who did not reflux (n = 32; P = 0.013) but not between those who were nonsurvivors (n = 7) and survivors (n = 32; P = 0.113). Horses in the reflux group had reduced duodenal contractility comparatively. There were no significant differences in duodenal contractions in the sequential days after the Day 1 scan or between duodenal contractions and surgical findings. A significant association was identified between duodenal contractions and survivors (P = 0.039; odds ratio 1.88). The main study limitations were the single centre design with consequent small numbers of horses included. The study did not account for other factors that may contribute to alterations in motility such as drug administration or stages of re-feeding. This preliminary study indicates that Day 1 (6–36 h post-operatively) duodenal contractions may predict reflux (>5 L/24 h beyond 24 h) and that increased duodenal contractions are associated with survival. However, there was no clear distinction or cut-off between groups. Future studies with greater numbers of horses yielding better statistical power are required.     

Upper respiratory signs associated with Anaplasma phagocytophilum infection in two horses

An adult Quarter Horse gelding (Case 1) was evaluated for tachypnoea and acute dysphagia. A 20-year-old Quarter Horse gelding (Case 2) was evaluated for respiratory stertor and severe, acute swelling of the head in the submandibular region. A physical examination, complete blood count, blood chemistry, upper airway endoscopy, and peripheral blood Anaplasma phagocytophilum polymerase chain reaction were completed for both horses. Both horses tested positive for A. phagocytophilum. The upper airway endoscopy for Case 1 revealed a feed contaminated pharynx, absent swallowing reflex, and left laryngeal hemiplagia. The upper airway endoscopy for Case 2 revealed severe diffuse pharyngeal swelling occluding the airway. Due to increased respiratory effort in Case 2, a tracheotomy was performed. In both horses, treatment consisted of intravenous oxytetracycline 6.6 mg/kg bwt i.v. q. 24 h for 2–3 days followed by minocycline 4 mg/kg bwt per os q. 12 h for 10–14 days. Both horses made full recoveries.     

Heritability estimates of fractures in Japanese Thoroughbred racehorses using a non‐linear model

Thoroughbred racehorses are produced by mating small numbers of Arabian stallions and native British mares, and have been improved by selection of horseracing performance for about 300 years. While these improvements led to good performance as racehorses, they exposed horses to numerous medical disorders, aggravated by extensive exercise. Fractures are frequent medical disorders in Thoroughbred racehorses. In this study, fracture heritability was estimated using 3,927 Japanese Thoroughbred racehorses to elucidate the risk of racehorse fractures. The heritability estimates of all examined fractures were low (h² = 0.06), while those of fractures in carpal bone and carpus (carpal bone plus distal radius) were moderate (h² = 0.37, 0.24, respectively). Fracture occurrence age for carpal bone and distal radius was both 3.3 years old and was younger than that for other fractures. These results indicated that a larger proportion of the variation in the studied population was due to genetic factors for carpal fractures than for other fractures, while the fractures at other bones were largely affected by environmental factors, correlated with the athlete period (number year in racing). These findings contribute to develop a management plan for suppressing racehorse fractures and improving horseracing safety.     

Hereditary equine regional dermal asthenia (HERDA) in Quarter Horses: A review of clinical signs,genetics and research

Hereditary equine regional dermal asthenia (HERDA) results from a genetic mutation which affects the skin and other tissues of Quarter Horses and horses with Quarter Horse lineage. The disease HERDA has an autosomal recessive mode of inheritance and has become a significant concern in the Quarter Horse industry due to the high frequency of heterozygote carriers. Affected homozygous horses appear normal at birth; however, within the first 2 years of life they usually acquire loose, hyperextensible skin and wounds which result in disfiguring scars either spontaneously or from minor trauma. Some severely affected horses also develop haematomas and seromas. Consequently, most affected horses are subjected to euthanasia at an early age. No treatment options other than palliative therapy currently exist. As part of a five panel test ( http://www.aqha.com/News/News-Articles/2013/April/04292013-Genetic-Testing.aspx ) the American Quarter Horse Association presently requires DNA testing for HERDA on all breeding stallions. There are currently no restrictions on registration of horses heterozygous or homozygous for the HERDA mutation. Due to the autosomal recessive nature of the disease, Quarter Horse mares and horses of all breeds from HERDA‐associated bloodlines should also be tested.     

Estimation of the probability for exceeding a threshold concentration of furosemide at various intervals after intravenous administration in horses

OBJECTIVE: To estimate the probability for exceeding a threshold concentration of furosemide commonly used for regulatory purposes after IV administration of furosemide in horses. ANIMALS: 12 mature healthy horses (6 Thoroughbreds and 6 Quarter Horses). PROCEDURE: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after administration of 250 or 500 mg of furosemide. Concentrations of furosemide were determined, using an ELISA. Concentration of furosemide was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic data, the probability for exceeding a concentration of 100 ng/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bootstrap approach was used to assess inherent variation in this estimated probability. RESULTS: The estimated probability of exceeding the threshold of 100 ng of furosemide/ml ranged from 11.6% at 4 hours to 2.2% at 5.5 hours after IV administration of 250 mg of furosemide/horse and 34.2% at 4 hours to 12.3% at 5.5 hours after IV administration of 500 mg of furosemide/horse. The probability of a horse being falsely identified in violation of regulatory concentrations was inversely associated with time and positively associated with dose. CONCLUSIONS AND CLINICAL RELEVANCE: Interhorse variability with respect to pharmacokinetics of furosemide will result in misclassification of some horses as being in violation of regulatory concentrations.     

Predictive value of hypoglycin A and methylencyclopropylacetic acid conjugates in a horse with atypical myopathy in comparison to its cograzing partners

Hypoglycin A (HGA) was detected in blood and urine of a horse suffering from atypical myopathy (AM; Day 2, serum, 8290 μg/l; urine: Day 1, 574, Day 2, 742 μg/l) and in its cograzing partners with a high variability (46–1570 μg/l serum). Over the period of disease, the level of the toxic metabolites (methylencyclopropylacetic acid [MCPA]‐conjugates) increased in body fluids of the AM horse (MCPA‐carnitine: Day 2, 0.246, Day 3, 0.581 μmol/l serum; MCPA‐carnitine: Day 2, 0.621, Day 3, 0.884 μmol/mmol creatinine in urine) and HGA decreased rapidly (Day 3, 2430 μg/l serum). In cograzing horses MCPA‐conjugates were not detected. HGA in seeds ranged from 268 to 367 μg/g. Although HGA was present in body fluids of healthy cograzing horses, MCPA‐conjugates were not detectable, in contrast to the AM horse. Therefore, increasing concentrations of MCPA‐conjugates are supposed to be linked with the onset of AM and both parameters seem to indicate the clinical stage of disease. However, detection of HGA in body fluids of cograzing horses might be a promising step in preventing the disease.     

Pharmacokinetics and selected pharmacodynamics of morphine and its active metabolites in horses after intravenous administration of four doses

The objective of the current study was to describe and characterize the pharmacokinetics and selected pharmacodynamic effects of morphine and its two major metabolites in horses following several doses of morphine. A total of ten horses were administered a single intravenous dose of morphine: 0.05, 0.1, 0.2, or 0.5 mg/kg, or saline control. Blood samples were collected up to 72 hr, analyzed for morphine, and metabolites by LC/MS/MS, and pharmacokinetic parameters were determined. Step count, heart rate and rhythm, gastrointestinal borborygmi, fecal output, packed cell volume, and total protein were also assessed. Morphine‐3 glucuronide (M3G) was the predominant metabolite detected, with concentrations exceeding those of morphine‐6 glucuronide (M6G) at all time points. Maximal concentrations of M3G and M6G ranged from 55.1 to 504 and 6.2 to 28.4 ng/ml, respectively, across dose groups. The initial assessment of morphine pharmacokinetics was done using noncompartmental analysis (NCA). The volume of distribution at steady‐state and systemic clearance ranged from 9.40 to 16.9 L/kg and 23.3 to 32.4 ml min^?1 kg^?1, respectively. Adverse effects included signs of decreased gastrointestinal motility and increased central nervous excitation. There was a correlation between increasing doses of morphine, increases in M3G concentrations, and adverse effects. Findings from this study support direct administration of purified M3G and M6G to horses to better characterize the pharmacokinetics of morphine and its metabolites and to assess pharmacodynamic activity of these metabolites.     

Pharmacokinetics and selected pharmacodynamics of romifidine following low‐dose intravenous administration in combination with exercise to quarter horses

Romifidine is an alpha‐2 adrenergic agonist used for sedation and analgesia in horses. As it is a prohibited substance, its purported use at low doses in performance horses necessitates further study. The primary goal of the study reported here was to describe the serum concentrations and pharmacokinetics of romifidine following low‐dose administration immediately prior to exercise, utilizing a highly sensitive liquid chromatography–tandem mass spectrometry assay that is currently employed in many drug testing laboratories. An additional objective was to describe changes in heart rate and rhythm following intravenous administration of romifidine followed by exercise. Eight adult Quarter Horses received a single intravenous dose of 5 mg (0.01 mg/kg) romifidine followed by 1 h of exercise. Blood samples were collected and drug concentrations measured at time 0 and at various times up to 72 h. Mean ± SD systemic clearance, steady‐state volume of distribution and terminal elimination half‐life were 34.1 ± 6.06 mL/min/kg and 4.89 ± 1.31 L/kg and 3.09 ± 1.18 h, respectively. Romifidine serum concentrations fell below the LOQ (0.01 ng/mL) and the LOD (0.005 ng/mL) by 24 h postadministration. Heart rate and rhythm appeared unaffected when a low dose of romifidine was administered immediately prior to exercise.     

Catastrophic scapular fractures in Californian racehorses: pathology, morphometry and bone density

Reasons for performing study: To enhance understanding of the nature and pathogenesis of scapular fractures in racehorses. Hypothesis: Scapular fractures in racehorses have a consistent configuration related to sites of pre‐existing stress modelling and remodelling. Methods: Fractured and intact scapulae collected post mortem were examined visually and with computed tomography (CT). Scapular fracture configuration, bone modelling changes and standardised CT morphometry and density measurements were recorded. Statistical comparisons were made between fractured, nonfractured contralateral and control scapulae. Results: Thirty‐nine scapulae from 10 Thoroughbred (TB) and 10 Quarter Horse (QH) racehorses were obtained. All 14 fractured scapulae (from 12 horses) had a consistent comminuted fracture configuration. A complete fracture coursed transversely through the neck of the scapula at the level of the distal aspect of the spine (8.9 ± 0.9 cm proximal to the lateral articular margin of the glenoid cavity). The distal fragment of 13 fractured scapulae was split into 2 major fragments by a fracture in the frontal plane that entered the glenoid cavity (2.8 ± 0.4 cm caudal to the cranial articular margin). Focal areas of periosteal proliferation and/or radiolucency were present in the distal aspect of the scapular spine of all fractured and intact contralateral scapulae, but less commonly (P<0.01) in intact scapula from horses without a scapular fracture. Fractured scapulae had 7–10% lower mean density and 46–104% greater density heterogeneity in the spine adjacent to the transverse fracture compared to control scapulae (P<0.03). Conclusions and clinical relevance: Thoroughbred and QH racehorses have a characteristic scapular fracture configuration that is associated with pre‐existing pathology of the distal aspect of the spine. This location is consistent with scapular stress fractures diagnosed in lame TB racehorses. Catastrophic fracture is the acute manifestation of a more chronic process. Consequently, there are opportunities for early detection and prevention of fatalities.