Pharmacokinetics of ketorolac tromethamine in horses after intravenous,intramuscular, and oral single‐dose administration

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are an integral component of equine analgesia, yet currently available NSAIDs are both limited in their analgesic efficacy and have adverse effects. The NSAID ketorolac tromethamine (KT) is widely used in humans as a potent morphine‐sparing analgesic drug but has not been fully evaluated in horses. The purpose of this study was to determine the pharmacokinetic profile of KT in horses after intravenous (i.v.), intramuscular (i.m.), and oral (p.o.) administration. Nine healthy adult horses received a single 0.5‐mg/kg dose of KT via each route of administration. Plasma was collected up to 48 h postadministration and analyzed for KT concentration using HPLC/MS/MS. Noncompartmental analysis of i.v. dosage indicated a mean plasma clearance of 8.4 (mL/min)/kg and an estimated mean volume of distribution at steady‐state of 0.77 L/kg. Noncompartmental analysis of i.v., i.m., and p.o. dosages indicated mean residence times of 2.0, 2.6, and 7.1 h, respectively. The drug was rapidly absorbed after i.m. and p.o. administration, and mean bioavailability was 71% and 57% for i.m. and p.o. administration, respectively. Adverse effects were not observed after i.v., i.m., and p.o. administration. More studies are needed to evaluate the analgesic and anti‐inflammatory properties of KT in horses.     

Pharmacokinetics of amikacin in plasma and selected body fluids of healthy horses after a single intravenous dose

Reasons for performing study: No studies have determined the pharmacokinetics of low‐dose amikacin in the mature horse. Objectives: To determine if a single i.v. dose of amikacin (10 mg/kg bwt) will reach therapeutic concentrations in plasma, synovial, peritoneal and interstitial fluid of mature horses (n = 6). Methods: Drug concentrations of amikacin were measured across time in mature horses (n = 6); plasma, synovial, peritoneal and interstitial fluid were collected after a single i.v. dose of amikacin (10 mg/kg bwt). Results: The mean ± s.d. of selected parameters were: extrapolated plasma concentration of amikacin at time zero 144 ± 21.8 µg/ml; extrapolated plasma concentration for the elimination phase 67.8 ± 7.44 µg/ml, area under the curve 139 ± 34.0 µg*h/ml, elimination half‐life 1.34 ± 0.408 h, total body clearance 1.25 ± 0.281 ml/min/kg bwt; and mean residence time (MRT) 1.81 ± 0.561 h. At 24 h, the plasma concentration of amikacin for all horses was below the minimum detectable concentration for the assay. Selected parameters in synovial and peritoneal fluid were maximum concentration (C_max) 19.7 ± 7.14 µg/ml and 21.4 ± 4.39 µg/ml and time to maximum concentration 65 ± 12.2 min and 115 ± 12.2 min, respectively. Amikacin in the interstitial fluid reached a mean peak concentration of 12.7 ± 5.34 µg/ml and after 24 h the mean concentration was 3.31 ± 1.69 µg/ml. Based on a minimal inhibitory concentration (MIC) of 4 µg/ml, the mean C_max : MIC ratio was 16.9 ± 1.80 in plasma, 4.95 ± 1.78 in synovial fluid, 5.36 ± 1.10 in peritoneal fluid and 3.18 ± 1.33 in interstitial fluid. Conclusions: Amikacin dosed at 10 mg/kg bwt i.v. once a day in mature horses is anticipated to be effective for treatment of infection caused by most Gram‐negative bacteria. Potential relevance: Low dose amikacin (10 mg/kg bwt) administered once a day in mature horses may be efficacious against susceptible microorganisms.     

Detection and genetic characterisation of vanA‐containing Enterococcus strains in healthy Lusitano horses

Lusitano horses were investigated in order to detect the presence of vancomycin‐resistant enterococci. vanA isolates showed high level vancomycin (Minimum inhibitory concentration; MIC ≥128 mg/l) and teicoplanin resistance (MIC 64 mg/l), as well as resistance to ciprofloxacin, erythromycin and tetracycline. The tet(L) and erm(B) genes, associated with tetracycline and erythromycin resistance, respectively, were found in all vanA isolates. The intestinal tract of Lusitano horses can be a potential reservoir for vanA‐containing enterococci.     

Ultrasound‐guided arthrocentesis of the temporomandibular joint in healthy adult horses is equivalent to blind arthrocentesis

Equine temporomandibular joint (TMJ) diseases are increasingly recognized as a problem for the well‐being and performance of horses. Diagnosis is confounded by overlap of clinical signs associated with pathology of the oral cavity, poll, and cervical vertebrae. Arthrocentesis for intra‐articular analgesia, sampling of synovial fluid, and medication is needed for diagnostic and therapeutic purposes. Ultrasound features of the normal TMJ and a blind arthrocentesis technique have been described, but a systematic approach to ultrasound‐guided (USG) arthrocentesis has not been reported. Ultrasound guidance allows visualization of the TMJ that may prove beneficial in cases when pathology, abnormal anatomy, or clinician inexperience make blind arthrocentesis difficult. We hypothesized that USG arthrocentesis would result in fewer needle repositions than blind arthrocentesis. We also aimed to assess synovial fluid parameters for normal equine TMJs. A prospective randomized method comparison with crossover experimental design compared the number of needle positionings required for accurate injection of the TMJ using each technique. Arthrocentesis technique and operator experience were tested using cadavers and two operators. Injection success was confirmed using CT. The radiologist then applied both techniques in normal live horses. No statistically significant difference was noted between arthrocentesis techniques or operators (P > .05). No complications were observed in live horses following either technique. Synovial fluid parameters were largely within the normal range expected for other synovial joints. Either blind or USG arthrocentesis of the equine TMJ can be performed with minimal prior operator experience. Ultrasound‐guided arthrocentesis is an alternative method and can be considered in cases with altered anatomy.     

Safety and efficacy of subcutaneous alpha-tocopherol in healthy adult horses

Vitamin E is essential for neuromuscular function. The primary treatment, oral supplementation with natural (‘RRR’) α-tocopherol, is not effective in all horses. The objectives of this pilot study were to evaluate the safety and efficacy of a subcutaneously administered RRR-α-tocopherol preparation. Horses were randomly assigned in a cross-over design to initially receive RRR-α-tocopherol (5000 IU/450 kg of 600 IU/mL) subcutaneously (n = 3) or orally (n = 3) or were untreated sentinels (n = 2). Tissue reactions following injection in Phase I of the study necessitated adjustment of the preparation with reduction of the RRR-α-tocopherol concentration to 500 IU/mL in Phase 2. Following an 8-week washout period, horses received the reciprocal treatment route with the new preparation (5000 IU/450 kg of 500 IU/mL). Serum, CSF and muscle α-tocopherol concentrations were determined by high-performance liquid chromatography over a 14-day period during each phase. Serum and CSF α-tocopherol concentrations increased significantly postinjection only when the 500 IU/mL product was administered (P<0.0001). There was no significant difference in the muscle concentration of α-tocopherol following either treatment. All eight horses had marked tissue reaction to subcutaneous injection, regardless of product concentration. Whilst we have demonstrated that this route may be a useful alternative to oral supplementation, the marked tissue reaction makes use of such products limited at this time to only the most refractory of cases.     

Short‐ and long‐term results following standing fracture repair in 34 horses

Reasons for performing study: Standing fracture repair in the horse is a recently described surgical procedure and currently there are few follow‐up data. This case series contains 2 novel aspects in the standing horse: repair of incomplete sagittal fractures of the proximal phalanx and medial condylar repair from a lateral aspect. Objectives: To describe outcome in a case series of horses that had lower limb fractures repaired under standing sedation at Rossdales Equine Hospital. Method: Case records for all horses that had a fracture surgically repaired, by one surgeon at Rossdales Equine Hospital, under standing sedation and local anaesthesia up until June 2011, were retrieved. Hospital records, owner/trainer telephone questionnaire and the Racing Post website were used to evaluate follow‐up. Results: Thirty‐four horses satisfied the inclusion criteria. Fracture sites included the proximal phalanx (incomplete sagittal fracture, n = 14); the third metacarpal bone (lateral condyle, n = 12, and medial condyle, n = 7); and the third metatarsal bone (lateral condyle, n = 1). One horse required euthanasia due to caecal rupture 10 days post operatively. Twenty horses (66.7% of those with available follow‐up) have returned to racing. Where available, mean time from operation to return to racing was 226 days (range 143–433 days). Conclusions: Standing fracture repair produced similar results to fracture repair under general anaesthesia in terms of both the number of horses that returned to racing and the time between surgery and race. Potential relevance: Repair of lower limb fracture in the horse under standing sedation is a procedure that has the potential for tangible benefits, including avoidance of the inherent risks of general anaesthesia. The preliminary findings in this series of horses are encouraging and informative when discussing options available prior to fracture repair.     

Effects of low-dose G-CSF formulation on hematology in healthy horses after long-distance transportation

The present study evaluated the effects of single-dose filgrastim on hematology in 16 healthy horses after long-distance transportation. Horses were assigned to receive filgrastim (0.23 µg/kg, SC, once; G-CSF group; n=8) or saline (0.9% NaCl) solution (0.3 ml, SC, once; control group; n=8) ≤ 1 hr before transportation. Horses were transported 2,530 km using commercial vans over the course of approximately 44 hr. Clinical examinations and hematologic analyses were performed on all horses before and after transportation. Because the post-transportation white blood cell counts and bacillary neutrophil to segmented neutrophil ratio were significantly higher in the G-CSF group, filgrastim may have promoted the mobilization of neutrophils from marrow. Filgrastim deserves a further study for efficacy in preventing horse shipping fever.     

Pharmacokinetics and pharmacodynamics of hydromorphone hydrochloride in healthy horses

ObjectivesTo determine the physiologic and behavioral effects and pharmacokinetic profile of hydromorphone administered intravenously (IV) to horses.Study designProspective, randomized, crossover study.AnimalsA group of six adult healthy horses weighing 585.2 ± 58.7 kg.MethodsEach horse was administered IV hydromorphone (0.025 mg kg^–1; treatment H0.025), hydromorphone (0.05 mg kg^–1; treatment H0.05) or 0.9% saline in random order with a 7 day washout period. For each treatment, physiologic, hematologic, abdominal borborygmi scores and behavioral data were recorded over 5 hours and fecal output was totaled over 24 hours. Data were analyzed using repeated measures anova with significance at p < 0.05. Blood samples were collected in treatment H0.05 for quantification of plasma hydromorphone and hydromorphone-3-glucuronide and subsequent pharmacokinetic parameter calculation.ResultsHydromorphone administration resulted in a dose-dependent increase in heart rate (HR) and systolic arterial pressure (SAP). HR and SAP were 59 ± 17 beats minute^–1 and 230 ± 27 mmHg, respectively, in treatment H0.05 at 5 minutes after administration. No clinically relevant changes in respiratory rate, arterial gases or temperature were observed. The borborygmi scores in both hydromorphone treatments were lower than baseline values for 2 hours. Fecal output did not differ among treatments and no evidence of abdominal discomfort was observed. Recorded behaviors did not differ among treatments. For hydromorphone, mean ± standard deviation for volume of distribution at steady state, total systemic clearance and area under the curve until the last measured concentration were 1.00 ± 0.29 L kg^–1, 106 ± 21 mL minute^–1 kg^–1 and 8.0 ± 1.5 ng hour mL^–1, respectively.Conclusions and clinical relevanceHydromorphone administered IV to healthy horses increased HR and SAP, decreased abdominal borborygmi and did not affect fecal output.     

Anaplastic malignant melanoma of the tail in non‐grey horses

Information regarding signalment, clinical findings, treatment and outcome of 5 previously reported cases of anaplastic malignant melanoma of the tail in non‐grey horses and of 5 additional cases are summarised. Age was recorded for 9 horses and mean age was 16 years, range 8–23 years. Gender was recorded for 8 horses and 6 of these 8 horses were male horses over 14 years of age. The most common coat colour was bay (6 horses). Other coat colours were palomino (one horse), chestnut (one horse) and black (one horse); coat colour of one non‐grey horse was not specified. Follow‐up information was available for 9 horses and only one horse, a palomino, survived more than 10 months following diagnosis and tail amputation. Surgical excision, including tail amputation and medical therapy with oral cimetidine, was not effective in non‐grey, non‐palomino horses. Tumour recurred on tail tissue remaining after amputation in 2 horses, widespread metastases were documented in 4 cases and metastasis was suspected at the time of death or euthanasia in 3 cases, including one case with amputation site regrowth. No subjective histopathological differences were detected in the palomino horse that survived as compared to horses of other coat colours. Findings suggest that anaplastic malignant melanoma of the tail in non‐grey horses is most often a very aggressive neoplasm, but that there are rare exceptions.