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Summary: Background: Clinical and anecdotal evidence exists for the use of orally administered prednisolone in the treatment of osteoarthritis in human patients; however, prednisolone is not commonly prescribed by this route of administration in horses for the treatment of osteoarthritis. Objectives: This preliminary study tested the hypothesis that orally administered prednisolone could be detected in equine synovial fluid 3 h after administration. Study design: Pre/post study. Methods: Six horses were used in this study. Blood was drawn pre‐prednisolone administration to assure that all horses were prednisolone free. Three hours after being given 400 mg prednisolone per os, an additional blood sample was taken, as well as samples from the radiocarpal (RC) and tibiotarsal (TT) joints. Samples were frozen and sent to the laboratory for the determination of the presence of prednisolone using liquid chromatography tandem mass spectrometry. Results: Prednisolone appeared in measurable concentrations in the blood (Mean = 92.655 ng/mL; SD = 54.95 ng/mL) and synovial fluid (RC Mean = 28.44 ng/mL; SD = 20.58 ng/mL and TT Mean = 20.33; SD = 15.67 ng/mL) of all horses when tested 3 h after administration. Main limitations: This study did not test for any possible therapeutic effects of oral prednisolone in osteoarthritis. It did not attempt to establish a therapeutic dosage for the medication, nor did it attempt to establish the pharmacokinetics of the medication. Conclusions: Orally administered prednisolone appears in equine blood and synovial fluid at 3 h post‐administration. Since it appears in joint fluid at concentrations that have been shown to be therapeutic for other corticosteroids, orally administered prednisolone may have potential value as a therapeutic agent in the treatment of equine osteoarthritis. [ABSTRACT FROM AUTHOR]

Summary: Background: The use of intra‐articular (IA) local anaesthetics has proven to be an effective means to treat post‐operative pain. The effects of local anaesthetics on equine chondrocytes are mixed with some studies reporting chondrodestruction and others no adverse effects. A liposomal formulation of bupivacaine is used in people and dogs by intra‐ and peri‐articular administration to provide up to 72 h of analgesia. The potential uses, side effects including chondrotoxicity, and likelihood of abuse (long‐term analgesic effects) has not been evaluated in horses. Objectives: Describe bupivacaine concentrations following IA administration and assess biomarkers as indicators of the effects of liposomal bupivacaine on chondrocytes in vivo. Study design: Parallel design. Methods: Sixteen exercised horses received a single IA administration of 0.12 mg/kg liposomal bupivacaine or 0.9% saline. Blood and urine samples were collected for 96 h post‐drug administration. Six horses treated with bupivacaine and those receiving saline, underwent daily arthrocentesis. Six additional bupivacaine treated horses underwent arthrocentesis at 96 h. Drug concentrations were measured using LC‐MS/MS and pharmacokinetic analyses performed. Immunoassays were used to measure markers of collagen degradation (C2C, C12C) and cartilage matrix synthesis (CPII, CS846) in synovial fluid. Results: The bupivacaine plasma elimination half‐life was 17.8 ± 5.42 and 11.9 ± 5.17 h for horses from which synovial fluid was collected daily and at 96 h respectively. Bupivacaine concentrations in the joint were still detectable at 96 h. Significant increases in C12C and C2C were noted at 96 h in horses undergoing arthrocentesis at 96 h only. CPII was increased at 48 h and CS846 at 24 and 48 h in horses sampled daily. Main limitations: Limited number of animals and absence of liposome control group. Conclusions: Sustained concentrations of IA bupivacaine suggest viability of this medication as an intra‐articular analgesic. Effects on equine chondrocytes need further study. [ABSTRACT FROM AUTHOR]

Summary: Background: Flumetasone is a potent corticosteroid reportedly used in horses to decrease inflammation associated with strenuous exercise. There are currently no reports describing the use of this drug in horses. Objectives: To describe the pharmacokinetics and effects on cortisol and eicosanoid concentrations, following administration of flumetasone to exercised horses. Study design: Parallel design. Methods: Twelve exercised horses received a single i.v. administration of 5 mg of flumetasone. Blood and urine samples were collected before and for 72 h post‐drug administration for determination of flumetasone and cortisol concentrations. Whole blood samples were collected at various time and challenged with lipopolysaccharide, calcium ionophore or methanol to induce ex vivo synthesis of eicosanoids. Concentrations of flumetasone, cortisol and eicosanoids were measured using LC‐MS/MS and pharmacokinetic/pharmacodynamic analysis performed. Results: Flumetasone was detected for 23.5 ± 1.73 h in blood. The volume of distribution at steady state, systemic clearance and elimination half‐life was 5.90 ± 0.200 L/kg, 30.7 ± 0.166 mL/min/kg and 4.84 ± 0.83 h respectively. Cortisol concentrations were still suppressed at last time point collected (72 h). For cortisol, Kin, Kout and the t1/2out were 30.3 ± 1.56 ng/mL × h, 0.331 ± 0.02 1/h and 2.1 h respectively. Stimulation with lipopolysaccharide resulted in a decrease in TXB2, PGF2, LTB4, 15‐HETE and 5‐HETE for up to 72 h and PGE2 for 24 h post‐flumetasone administration. Stimulation of whole blood with calcium ionophore resulted in a decrease in LTB4 for up to 6 h and 15‐HETE at 8 h. Main limitations: Lack of sample collection for determination of biomarker concentrations beyond 72 h and the use of a single sample for determination of baseline cortisol concentrations. Conclusions: Flumetasone is rapidly cleared from blood following administration to horses. It is a potent anti‐inflammatory with prolonged effects on production of cortisol and other inflammatory mediators. [ABSTRACT FROM AUTHOR]

Summary: Background: Intra‐articular use of corticosteroids is commonplace in performance horses. Isoflupredone acetate (IPA) is one of four Food and Drug Administration approved corticosteroids for intra‐articular use in horses. The lack of published reports describing the efficacy and duration of effects of this drug warrant further study. Objectives: To assess the effects of intra‐articular administration of IPA on the expression of selected anti‐ and pro‐inflammatory and structural matrix genes following intra‐articular administration to exercised Thoroughbred horses and to correlate these effects with drug concentrations. Study design: Block design in vivo experiment. Methods: Twelve exercised horses received either a single intra‐articular administration of 8 mg of IPA or 0.9% saline solution. Synovial fluid samples were collected prior to and up to 42 days post drug administration from the treated joints. Microarray and qRT‐PCR analysis were used to assess changes in expression levels of various inflammatory and structural genes post drug administration. Results: On microarray analysis, 855, 23,358 and 26,411 genes had a measurable fold change (increase or decrease in expression levels) when comparing baseline samples to 24 h, baseline samples to day 7 and 24 h samples to day 7, respectively. Of the genes selected for further study by qRT‐PCR analysis, expression of ANXA‐1 (lipocortin) was significantly increased and IL23A and MMP1 and MMP9 significantly decreased following IPA administration. Expression levels of collagen genes were not significantly different from baseline. Main limitations: Limitations include the use of a noninflammatory model as results may differ in the presence of an acute inflammatory insult and the inability to measure protein concentrations of inflammatory mediators due to limited synovial fluid sample volume. Conclusions: Expression relative to baseline, for both inflammatory and matrix genes for up to 42 days post IPA administration, suggests a prolonged effect relative to detection time in both plasma and synovial fluid. [ABSTRACT FROM AUTHOR]

Summary: Background: Due to the high prevalence of EIPH in racehorses and its potential impact on the horse's health, furosemide administration is permitted up to 4‐h prior to post time in most North American racing jurisdictions. Anecdotal reports suggest that administration of furosemide 24‐h prior to strenuous exercise may be equally effective in decreasing the severity of EIPH. Objectives: To 1) compare the efficacy of furosemide in reducing the presence and severity of EIPH when administered 4‐ or 24‐h prior to strenuous exercise 2) characterise electrolyte and blood parameters following administration of furosemide at 4‐ and 24‐h prior to exercise. Study design: 3‐way crossover. Methods: Fifteen Thoroughbred racehorses received 5 mL of 0.9% NaCl or 250 mg of furosemide either 4‐ or 24‐h prior to a 5‐furlong simulated race. Blood samples were collected prior to and post‐run for determination of furosemide, lactate, haemoglobin and electrolyte concentrations. One‐hour post‐race, an endoscopic exam and bronchoalveolar lavage (BAL) were performed. Horses were assigned an EIPH score based on predetermined criteria and the number of red blood cells in BAL fluid was determined. Results: Endoscopic EIPH scores were lower in the 4‐h vs. the 24‐h (P = 0.03) furosemide groups. RBC counts in BAL fluid were lower in the 4‐h furosemide vs. saline treatment groups (P = 0.01) but no difference was noted between the saline and 24‐h furosemide groups (P = 0.3), nor between the 4‐ and 24‐h groups (P = 0.5). Main limitations: Small sample size and large range of running times for the 5‐furlong work. Conclusions: While none of the treatments prevented EIPH, endoscopic scores and RBC counts in BAL fluid support the efficacy of furosemide in reducing the severity of EIPH. Endoscopic scores were lower in the 4‐h furosemide group compared with 24‐h administration. Red blood cell counts were lower in the 4‐h furosemide group compared with saline treatment. [ABSTRACT FROM AUTHOR]

Reason for performing study The frequent use of intra-articular triamcinolone acetonide ( TA) in performance horses warrants further study of the duration of as well as the beneficial and detrimental effects on gene expression associated with administration. Objectives To assess the effects of intra-articular administration of TA on the expression of selected anti- and proinflammatory and structural matrix genes following its administration into joints of exercised Thoroughbred horses and to correlate these effects with plasma and synovial fluid drug concentrations. Study design Block design experiment. Methods Eight exercised horses received a single intra-articular administration of 9 mg of TA. Synovial fluid samples were collected from the treated and contralateral joints prior to and up to 49 days following drug administration. Microarray and quantitative reverse transcription polymerase chain reaction analysis were used to assess changes in expression levels of various inflammatory and structural genes post drug administration. Results Drug concentrations in plasma and synovial fluid, were no longer quantifiable by 6 and 28 days following drug administration respectively. In total, the expression level of 5490 genes were significantly altered on micro array analysis, following intra-articular TA administration. Of the genes selected for further study by quantitative reverse transcription polymerase chain reaction analysis, significant changes in inflammatory genes (annexin type 1, cyclooxygenase-1 and tumour necrosis factor stimulated gene 6) and structural genes (collagen and aggrecan) were noted. Conclusions This study supports the use of synovial fluid as a biological matrix for studying the effects of corticosteroids on gene expression. For the majority of genes studied the effects on expression relative to baseline for both inflammatory and matrix genes were prolonged relative to plasma and synovial fluid TA concentrations. Downregulation of collagen gene expression warrants the careful use of TA in horses. [ABSTRACT FROM AUTHOR]