Urine analysis in horses involves the examination of urine to assess the health and physiological status of the animal. This diagnostic tool provides insights into the renal function, hydration status, and potential presence of systemic diseases. Key parameters evaluated in equine urine analysis include pH, specific gravity, protein levels, glucose, ketones, and the presence of blood or sediment. Variations in these parameters can indicate metabolic disorders, infections, or other health issues. This page compiles peer-reviewed research studies and scholarly articles that explore the methodologies, findings, and clinical implications of urine analysis in equine veterinary practice.
So YM, Wong JKY, Wong ASY, Tse ATL, Wan TSM, Ho ENM.The erythropoietin mimetic peptide 1 linear form (EMP1-linear), GGTYSCHFGPLTWVCKPQGG-NH , was identified in an unknown preparation consisting of white crystalline powder contained in sealed glass vials using ultrahigh performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). The white crystalline powder, allegedly used for doping racehorses, was found to contain around 2% (w/w) of EMP1-linear. EMP1-linear can be cyclised in equine plasma at physiological temperature of 37°C by forming an intramolecular disulfide bond to give EMP1, which is a well-known erythropoiesis st...
Timms M, Botteon A, Manos C, Griffin J, Levina V, Steel R.Gonadotropin-releasing hormone (GnRH) and its synthetic analogues are considered banned substances by the racing industry. GnRH is used as a pharmaceutical to regulate the female oestrous cycle, but the hormone is also thought to increase the production of testosterone in male animals. Using liquid chromatography in conjunction with high-resolution mass spectrometry (LC-HRMS) and data-independent acquisition (DIA), a method is presented for the detection of intact and truncated peptides of GnRH and its analogues down to the low picogram level in equine urine. The study of the catabolism of GnR...
Cloteau C, Dervilly G, Loup B, Delcourt V, Kaabia Z, Bagilet F, Groseille G, Dauriac K, Fisher S, Popot MA, Garcia P, Le Bizec B, Bailly-Chouriberry L.Despite their ban, Anabolic Androgenic Steroids (AAS) are considered as the most important threat for equine doping purposes. In the context of controlling such practices in horse racing, metabolomics has emerged as a promising alternative strategy to study the effect of a substance on metabolism and to discover new relevant biomarkers of effect. Based on the monitoring of 4 metabolomics derived candidate biomarkers in urine, a prediction model to screen for testosterone esters abuse was previously developed. The present work focuses on assessing the robustness of the associated method and def...
Maxwell L, McCarrel TM, Hay S, Cole C.The antifibrinolytic agent aminocaproic acid (ACA) is occasionally used prior to episodes of intense training in racehorses suffering from exercise-induced pulmonary hemorrhage. Although a previous study indicated that the drug is cleared rapidly in horses, some racetrack practitioners claim that recent adverse analytical findings for ACA in postrace samples were from ACA administrations 5-7 days before the race. The purpose of this study was to re-examine the pharmacokinetics of ACA in horses to address this apparent conundrum. Eight exercise-conditioned thoroughbred horses were administere...
Schenk I, Broussou D, Roques B, Lagershausen H, Machnik M, Röttgen H, Toutain PL, Thevis M.The combination of sulfadoxine (SDO) with trimethoprim (TMP) is widely used in veterinarian medicine. The aim of the present study was to compare excretion profiles and detection time windows of SDO and TMP in plasma and urine by means of a validated quantitative method. Eight horses received a single intravenous (i.v.) dose of 2.7 mg TMP and 13.4 mg SDO per kg bodyweight. Plasma and urine samples were collected up to 15 and 70 days post-administration, respectively. While urine samples underwent an enzymatic hydrolysis, plasma samples were proteolysed before further analysis. After solid-...
You Y, Proctor RM, Haughan J, Missanelli JR, Robinson MA.Fentanyl, a powerful synthetic mu opioid receptor agonist, is banned in equine sports by the Association of Racing Commissioners International and the Fédération Équestre Internationale. The presence of fentanyl in equine blood has been confirmed during routine post-race screening for doping substances in the authors' laboratory. While fentanyl can be detected and confirmed in blood, it is rapidly metabolized, and screening for the metabolite N-[1-(2-phenethy-4-piperidinyl)] maloanilinic acid (PMA) in equine urine is expected to allow for a longer detection time. In this study, a quantitati...
Karatt TK, Sathiq MA, Laya S, Karakka Kal AK, Subhahar MB, M P MA, Philip M, Graiban FM, Caveney MR.Since 2010, there has been an increasing number of adverse analytical findings related to selective androgen receptor modulators (SARMs) in competitive sports. It emphasizes the importance of comprehensive doping control analytical procedures that are capable of detecting SARM misuse. Methods: In this study, it is described how LY2452473, a SARM, was metabolized in thoroughbred horses after a single-dose oral administration and in vitro with equine liver microsome preparations. An investigation of the metabolism of LY2452473 in horses' urine, plasma, and hair matrices was carried out during th...
Harding C, Viljanto M, Habershon-Butcher J, Taylor P, Scarth J.YK-11 is a steroidal selective androgen receptor modulator, a compound class prohibited in both equine racing and human sports because of their potentially performance enhancing properties. YK-11 is easily accessible via internet-based supplement vendors making this compound a possible candidate for doping; however, its phases I and II metabolism has not yet been reported in the horse. The purpose of this study was to investigate the in vivo metabolites of YK-11 in urine and plasma following oral administration with three daily doses of 50 mg to two Thoroughbred horses. In vitro incubations ...
Knych HK, Weiner D, Harrison L, McKemie DS.Intra-articular corticosteroids, such as isoflupredone acetate, are commonly used in the treatment of joint inflammation, especially in performance horses. Following administration in a non-inflamed joints blood concentrations of isoflupredone were low and detectable for only a short period of time post-administration compared to synovial fluid concentrations. For some drugs, inflammation can affect pharmacokinetics, therefore, the goal of the current study was to describe the pharmacokinetics of isoflupredone acetate following intra-articular administration using a model of acute synovitis. S...
Knych HK, Mama K, Oakleaf M, Harrison LM, McKemie DS, Kass PH.The goal of this study was to determine plasma, urine, and synovial fluid concentrations and describe the effects on biomarkers of cartilage toxicity following intra-articular dexmedetomidine administration to horses. Methods: 12 research horses. Methods: Horses received a single intra-articular administration of 1 μg/kg or 5 μg/kg dexmedetomidine or saline. Plasma, urine, and synovial fluid were collected prior to and up to 48 hours postadministration, and concentrations were determined. The effects on CS846 and C2C were determined in synovial fluid at 0, 12, and 24 hours postadministration...
Kabil E, Göktaş EF, Güneş E, Yatanaslan L, Zor TA, Tektaş MH, İnceman B, Tufan M.A recent trend in the use of high-resolution accurate mass screening (HRAMS) for doping control testing in both human and animal sports has emerged owing to significant improvement in high-resolution mass spectrometry in terms of sensitivity, mass accuracy, mass resolution and mass stability. Several HRAMS methods have been reported for the detection of multidrug residues in human or equine urine. These improved analytical technologies have led to changes in the use of prohibited substances, and the administration of more than one substance at low concentrations as a "cocktail" has become one ...
Sandbaumhüter FA, Aerts JT, Theurillat R, Andrén PE, Thormann W, Jansson ET.The chiral drug ketamine has long-lasting antidepressant effects with a fast onset and is also suitable to treat patients with therapy-resistant depression. The metabolite hydroxynorketamine (HNK) plays an important role in the antidepressant mechanism of action. Hydroxylation at the cyclohexanone ring occurs at positions 4, 5, and 6 and produces a total of 12 stereoisomers. Among those, the four 6HNK stereoisomers have the strongest antidepressant effects. Capillary electrophoresis with highly sulfated γ-cyclodextrin (CD) as a chiral selector in combination with mass spectrometry (MS) was us...
Philip M, Karakka Kal AK, Subhahar MB, Karatt TK, Mathew B, Perwad Z, Graiban FM, Caveney MR, Sayed R, Kadry AM.According to previous research, aminorex is the major metabolite of levamisole; however, in the screening of levamisole-positive racehorse urine and plasma samples, aminorex could only be detected in trace amounts or not at all. In forensic laboratories, hydroxy levamisole and its phase II conjugates make it easier to confirm levamisole misuse and to differentiate between the abuse of levamisole and aminorex. This study aimed to identify the major levamisole metabolites that can be detected along with the parent drug. Methods: The study describes levamisole and its metabolites in thoroughbred ...
Jahn P, Dobešová D, Brumarová R, Tóthová K, Kopecká A, Friedecký D.Equine atypical myopathy (AM also referred to as multiple acyl-CoA dehydrogenases deficiency [MADD]) is thought to be caused by toxins metabolized from hypoglycin A (HGA) and méthylènecyclopropylglycine (MCPrG). HGA is contained in the seeds and seedlings of the sycamore tree (Acer pseudoplatanus); MCPrG has so far only been confirmed in seeds. Among other things, these substances can disrupt the fatty acids β-oxidation pathway with the subsequent accumulation of certain acylcarnitines. The tentative diagnosis is based on anamnesis and clinical signs and can be verified by the detection of ...
Ishii H, Shibuya M, Leung GN, Yamashita S, Nagata SI, Kushiro A, Sakai S, Toju K, Okada J, Kawasaki K, Kusano K, Kijima-Suda I.For the purpose of doping control, this is the first report of accurate quantification of four critical structural isomers of nicotine metabolites (trans-3'-hydroxycotinine, cis-3'-hydroxycotinine, 5'-hydroxycotinine, and N'-hydroxymethylnorcotinine) in equine plasma and urine for the establishment of their elimination profiles. Besides, the pharmacokinetic studies of trans-3'-hydroxycotinine and N'-hydroxymethylnorcotinine in equine plasma and urine are also presented for the first time. Methods: The accurate quantification methods of the aforementioned four structural isomers in horse plasma...
Current drug metabolismAugust 27, 2022
Volume 23, Issue 10 850-865 doi: 10.2174/1389200223666220825093945
Ishii H, Shibuya M, Kusano K, Sone Y, Kamiya T, Wakuno A, Ito H, Miyata K, Sato F, Kuroda T, Yamada M, Leung GN.Vadadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitor, is a substance which carries a lifetime ban in both horse racing and equestrian competition. A comprehensive metabolic study of vadadustat in horses has not been previously reported. Objective: Metabolism and elimination profiles of vadadustat in equine plasma and urine were studied for the purpose of doping control. Methods: A nasoesophageal administration of vadadustat (3 g/day for 3 days) was conducted on three thoroughbred mares. Potential metabolites were comprehensively detected by differential analysis of ful...
Knych HK, Finno CJ, Katzman S, Ryan D, McKemie DS, Kass PH, Arthur RM.Clodronate is a potent antiresorptive agent labelled for use in horses over 4 years of age, for the treatment of navicular syndrome. Concerns regarding the extra-label use of clodronate in equine athletes, such as racehorses, have been raised as inhibition of osteoclast activity by clodronate has been postulated to interfere with normal bone healing, which is imperative to the repair of microfractures. The paucity of data describing the long-term pharmacokinetics of clodronate and effects on biomarkers of bone resorption necessitates further study. Objective: (1) To determine clodronate conc...
Bolwell C, Gee E, Adams B, Collins-Emerson J, Scarfe K, Nisa S, Gordon E, Rogers C, Benschop J.The objectives of this study were to determine if horses located near an outbreak of leptospirosis in alpacas had titres indicative of a previous or current infection and, if so, to determine the magnitude in change of titres over time. Further, the objective was to determine if horses with high titre results were shedding in their urine. Blood samples were collected from twelve horses located on or next to the farm with the outbreak in alpacas, on day zero and at four subsequent time points (two, four, six and nine weeks). The microscopic agglutination test was used to test sera for five se...
Göktaş EF, Kabil E, Yatanaslan L, Güneş E, Dirikolu L.Caffeine is a naturally occurring alkaloid and it is metabolized to paraxanthine, theophylline and theobromine. Analysis of caffeine and its metabolites is challenging since the metabolites theophylline and paraxanthine generate similar product and precursor ions. In this study, a new method was developed for the simultaneous analysis of caffeine, paraxanthine, theobromine and theophylline in horse urine using gas chromatography-mass spectrometry (GC-MS). Urine samples were treated using solid-phase extraction followed by the elution with dichloromethane-isopropanol (90:10) after the pH was ad...
van Spijk JN, Beckmann K, Wehrli Eser M, Boxler M, Stirn M, Rhyner T, Kaelin D, Saleh L, Schoster A.Polymyxin B (PolyB) is used to treat endotoxemia in horses; neurologic and nephrogenic adverse effects occur in humans. Objective: To describe PolyB adverse effects in horses. Methods: Five healthy horses (ataxia 0/5), 1 horse with cervical osteoarthritis (ataxia 1/5). Methods: Prospective blinded randomized cross-over trial; 3-weeks wash out. Horses received PolyB (PolyB 6000 IU/kg IV, 7 doses q12h, n = 6) and PolyB/gentamicin (PolyB 6000 IU/kg IV, q12h 7 doses; gentamicin 10 mg/kg IV q24h 4 doses n = 4, or q12-24 h 5 doses because of an additional erroneous dose, n = 2). Daily n...
Machin J, Brewer K, Morales-Briceno A, Fenger C, Maylin G, Tobin T.Zilpaterol is a β2-adrenergic agonist medication approved in certain countries as a cattle feed additive to improve carcass quality. Trace amounts of Zilpaterol can transfer to horse feed, yielding equine urinary "identifications" of Zilpaterol. These "identifications" occur because Zilpaterol is highly bioavailable in horses, resistant to biotransformation and excreted as unchanged Zilpaterol in urine, where it has a 5 day or so terminal half-life.In horses, urinary steady-state concentrations are reached 25 days (5 half-lives) after exposure to contaminated feed. Zilpaterol readily presen...
Haughan JE, Missanelli JR, You Y, Stefanovski D, Soma LR, Robinson MA.Glaucine, an aporphine alkaloid with anti-tussive, anti-inflammatory, and anti-nociceptive properties, has been identified in post-race samples from racehorses. To investigate pharmacokinetics of glaucine in horses, a three-way crossover study of intravenous and oral glaucine (0.1 mg/kg) and orally administered tulip poplar shavings (50 g shavings = 0.001 mg/kg glaucine) was performed in six horses. A two-compartment model best described IV administration with alpha ( ) and beta ( ) half-life lives of 0.3 (0.1-0.7) and 3.1 (2.4-7.8) h, respectively. The area under the curve ( ) was ...
Elbourne M, Cawley A, Stanley S, Bowen C, Fu S.Equine urine analysis has evolved over time to detect thousands of urinary compounds for doping control in the horse racing industry. The longitudinal assessment of 3-methoxytyramine to tyramine ratio (3-MT/T) values in equine urine by GC-MS profiling was investigated to support the Racing NSW Equine Biological Passport (EBP) for detection of dopaminergic manipulation in racehorses. This involved comparison of routine urine samples to administration studies of Sinemet, a common Parkinson's disease medication containing levodopa. Using an endogenous reference compound (ERC) in a urinary ratio e...
Olsen E, van Galen G.Chronic kidney disease (CKD) is rare in horses with an overall prevalence reported to be 0.12%. There is often a continuum from Acute Kidney Injury (AKI) to CKD, and patients with CKD may be predisposed to episodes of AKI. The most common clinical signs are non-specific with weight loss, polyuria/polydipsia and ventral edema. Less common clinical signs are poor appetite and performance, dull hair coat, oral ulcerations, gastro-intestinal ulceration, gingivitis, dental tartar and diarrhea. Rarely, horses may develop forebrain signs. Creatinine increases when at least 2/3 of kidney function have...
Meny P, Iglesias T, Menéndez C, Quintero J, Ríos C, Ashfield N, Ferreira O, Mosca V, De Brun L, Ortiz G, De Vries I, Varela G, Schelotto F.To investigate seroprevalence of anti-Leptospira antibodies in equines and associated workers in Uruguay, 891 equine and 150 human sera were drawn; 212 equine urine samples were also taken for culture. Environmental conditions and equine raising or managing practices were recorded in all 72 visited establishments; epidemiological information was obtained from each worker. Microscopic agglutination technique (MAT) was performed with 10 Leptospira strains for equines and 18 for human sera, that were also studied with IgM indirect immunofluorescence (IgM-IIF). Equine titres ≥100 were considered...
Cutler C, Viljanto M, Taylor P, Habershon-Butcher J, Van Eenoo P.Ibutamoren mesylate, or MK-0677, is an orally active, nonpeptide growth hormone secretagogue that has been developed to stimulate excretion of endogenous growth hormone. It has been evaluated for the treatment of a range of clinical conditions but is not available therapeutically. Nonetheless, MK-0677 is widely available to purchase online, sold as 'supplement' products. The mode of action and relative ease of purchase make MK-0677 a potential threat with regard to sports doping. The aim of this study was to investigate the metabolism of MK0677 in the horse following in vitro incubation and or...
Barrell EA.Polyuria and polydipsia are rare, but significant, manifestations of several different diseases of horses. Causes can be endocrine, iatrogenic, psychogenic, infectious, or toxic in nature and can also be due to primary renal disease or diseases of other organs, such as the liver. Although numerous causes of polyuria and polydipsia in horses exist, the most common conditions include chronic kidney disease, pituitary pars intermedia dysfunction, and psychogenic polydipsia with secondary polyuria. Additional testing is dictated by history, other clinical signs, and the results of blood work and/o...
Divers TJ.Nephrotoxic and hemodynamically mediated disorders are the most common causes of acute renal failure (ARF) in horses and foals. Leptospira spp. is the most common infectious cause of ARF. Initial treatments for ARF include elimination of nephrotoxic drugs, correction of predisposing disorders, and fluid therapy to promote diuresis. Horses and foals with polyuric ARF often have a good prognosis, while those with oliguric or anuric ARF have a guarded to poor prognosis. When fluid therapy is unsuccessful in improving urine production, various drugs treatments have been used in an attempt to incre...
Ishii H, Leung GN, Yamashita S, Nagata SI, Kushiro A, Sakai S, Toju K, Okada J, Kawasaki K, Kusano K, Kijima-Suda I.The use of nicotine stimulants in horses is generally banned in horse racing and equestrian sports-accidental consumption of tobacco products is one of the possible causes of nicotine exposure in horses. The authors recently reported a comprehensive metabolic study of nicotine in equines, differentiating between nicotine exposure and sample contamination by means of a nicotine biomarker trans-3'-hydroxycotinine. To identify potential biomarkers for the differentiation of genuine nicotine administration and consumption of tobacco products, tobacco leaves (equivalent to 250 mg of nicotine) wer...
Dunkel B, Palmer JE, Olson KN, Boston RC, Wilkins PA.Foals may present to a referral hospital with the primary diagnosis of uroperitoneum (UP), or they may develop UP while hospitalized for other reasons. Historical, physical, laboratory, and diagnostic variables of foals presenting with UP were compared to those developing UP while hospitalized. Emphasis was placed on the presence of electrolyte abnormalities, evidence of sepsis or infection, and development of anesthetic complications during surgical correction of the defect. Foals developing UP while in the hospital frequently had a history of dystocia and presented at a very young age (< ...
Songsermsakul P, Böhm J, Aurich C, Zentek J, Razzazi-Fazeli E.Concentration profile of zearalenone (ZON) and its metabolites in plasma, urine and faeces samples of horses fed with Fusarium toxin-contaminated oats is described. In plasma, β-zearalenol (β-ZOL) was detected at high levels on day 10 of the study (3.21-6.24 μg/l). β-Zearalenol and α-zearalenol were the major metabolites in urine. Zearalenone, α-ZOL and β-ZOL were predominantly found in faeces. Zearalanone could also be detected in urine (1.34-5.79 μg/l) and faeces (1 μg/kg). The degree of glucuronidation was established in all sample types, approximately 100% in urine and plasm...
Thurmon JC, Steffey EP, Zinkl JG, Woliner M, Howland D.Xylazine given IV at doses of 0.5, 1.0, and 1.5 mg/kg to mares caused a significant (P less than 0.05) dose-related increase in serum glucose concentration and urine volume. Serum glucose concentrations as much as 150 mg/dl were recorded in mares after they were given the largest xylazine dose. The greatest urine volume, similar to changes in peak glucose concentration, always occurred during the first hour after dosing with xylazine and averaged 1.82, 3.93, and 5.68 ml/kg/hour after the 0.5-, 1.0-, and 1.5-mg/kg doses, respectively, were given. Urine osmolality and specific gravity were signi...
Guan F, Uboh C, Soma L, Hess A, Luo Y, Tsang DS.Beclomethasone dipropionate (BDP) is a potent pro-drug to beclomethasone (BOH) and is used in the treatment of chronic and acute respiratory disorders in the horse. The therapeutic dose of BDP (325 microg per horse) by inhalation results in very low plasma and urinary concentrations of BDP and its metabolites that pose a challenge to detection and confirmation by equine forensic laboratories. To solve this problem, a method involving the use of a liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) was developed for the detection, confirmation and quantification of the analyt...
Schott HC, Hodgson DR, Bayly WM.The effects of exercise on urinary excretion of red blood cells, pigments (haemoglobin and myoglobin) and protein were studied in 8 mares performing treadmill exercise at speeds eliciting 40, 60 and 95% of the maximal oxygen consumption (VO2max). Gross haematuria and pigmenturia were observed in all horses during exercise at the 2 higher intensities, while these findings were detected in only one of 8 mares during exercise at 40% of the VO2max. For the remaining 7 mares exercised at 40% of the VO2max, increased urinary excretion of red blood cells (RBCs) and pigments was evident after centrifu...
Ensink JM, Klein WR, Mevius DJ, Klarenbeek A, Vulto AG.The pharmacokinetics of ampicillin and amoxicillin following intravenous administration at a dose rate of 15 and 10 mg/kg respectively were studied in four healthy adult horses. Pharmacokinetics of pivampicillin and amoxicillin were studied after oral administration to four healthy adult horses. Pivampicillin, a prodrug of ampicillin, was administered orally to starved and fed horses at a dose rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg ampicillin. Amoxicillin was administered orally to starved horses only, at a dose rate of 20 mg/kg. Ampicillin and amoxicillin con...
Schott HC, Esser MM.Clinicopathologic evaluation of renal function and renal disease in sick adult horses remains grounded in detection of azotemia, assessment of serum and urine electrolyte concentrations, and evaluation of urinalysis findings, including specific gravity, reagent strip analysis, and sediment examination. Because increases in serum or plasma urea nitrogen and creatinine concentrations are insensitive indicators of a decreased glomerular filtration rate, there is considerable interest in identifying novel biomarkers of renal function or injury in blood and urine, with serum symmetric dimethylargin...
Letendre LT, Tessman RK, McClure SR, Kvaternick VJ, Fischer JB, Hanson PD.To determine pharmacokinetic parameters and variables, firocoxib concentrations in urine and plasma, urine-to-plasma ratios, and the urine depletion profile of firocoxib and to evaluate whether the pharmacokinetic behavior of firocoxib was governed by linear processes after multiple doses of firocoxib were administered IV and orally. Methods: 6 healthy female horses (5 Paint horses and 1 Quarter Horse) in experiment 1 and 12 healthy male and female horses in experiment 2. Methods: In experiment 1, 6 horses were orally administered firocoxib paste once daily for 12 consecutive days, and plasma ...
Ho EN, Leung DK, Wan TS, Yu NH.This paper reports two highly efficient liquid chromatography-mass spectrometry (LC-MS) methods for the screening of anabolic steroids, corticosteroids, and acidic drugs for the purpose of doping control in equine sports. Sample extraction was performed using a mixed-mode C8-SCX solid-phase extraction (SPE) cartridge. The first eluted fraction (acidic/neutral fraction) was base-washed and the resulting organic extract was used for the screening of anabolic steroids and corticosteroids by LC-MS using multiple reaction monitoring (MRM) in the positive electrospray ionisation (ESI) mode. The rema...
Trim CM, Hanson RR.The intravenous administration of xylazine (1.1 mg/kg bodyweight) in six ponies resulted in a significant increase in urine output over two hours, with maximum flow occurring between 30 and 60 minutes after injection. Urine specific gravity, osmolality and glucose concentration decreased. Renal clearance of endogenous creatinine was unchanged. Significant increases in the excretion of potassium and chloride occurred. Plasma glucose concentration was increased 30 minutes after the administration of xylazine by a mean value of 37 per cent. Serum osmolality and sodium, potassium and chloride conc...
Ho EN, Leung DK, Leung GN, Wan TS, Wong AS, Wong CH, Soma LR, Rudy JA, Uboh C, Sams R.Administration studies of levamisole in horses were carried out using two different levamisole preparations, namely, levamisole hydrochloride oral bolus and levamisole phosphate injectable solution. These preparations were analysed in detail for the presence of aminorex-like impurities. Both levamisole preparations were found to contain 1-(2-mercaptoethyl)-4-phenyl-2-imidazolidinone (I) and 4-phenyl-2-imidazolidinone (II) as degradation impurities, but neither aminorex nor rexamino was detected in these preparations. After the administration of these preparations to horses, aminorex, rexamino,...
Chan GH, Ho EN, Leung DK, Wong KS, Wan TS.The use of anabolic androgenic steroids (AAS) is prohibited in both human and equine sports. The conventional approach in doping control testing for AAS (as well as other prohibited substances) is accomplished by the direct detection of target AAS or their characteristic metabolites in biological samples using hyphenated techniques such as gas chromatography or liquid chromatography coupled with mass spectrometry. Such an approach, however, falls short when dealing with unknown designer steroids where reference materials and their pharmacokinetics are not available. In addition, AASs with fast...
Siwinska N, Zak A, Slowikowska M, Niedzwiedz A, Paslawska U.There are limited options to diagnose acute kidney injury (AKI) in horses. Symmetric dimethylarginine (SDMA) is routinely used in human and small animal medicine. The aim of this study was to assess serum SDMA concentrations in healthy horses and horses with AKI. The objective of this study was to evaluate the association of: 1) age, 2) sex, 3) body weight and 4) serum creatinine and urea levels on serum SDMA concentrations. Fifty-three healthy horses, including 17 foals (2-6 months of age) and 36 adult horses (3-29 years of age), and 23 horses with AKI were included in the study based on ...
Lester GD, Merritt AM, Kuck HV, Burrow JA.Intravenous (IV) and intragastric (IG) administration of fluid therapy are commonly used in equine practice, but there are limited data on the systemic, renal, and enteric effects. Objective: IV fluid administration will increase intestinal and fecal hydration in a rate-dependent manner after hypertonic dehydration, but will be associated with significant urinary water and electrolyte loss. Equivalent volumes of IG plain water will result in comparatively greater intestinal hydration with less renal loss. Methods: Six Thoroughbred geldings. Methods: Experimental study. 6 by 6 Latin square desi...
Ho EN, Yiu KC, Wan TS, Stewart BD, Watkins KL.Anti-diabetics such as sulfonylurea and thiazolidinedione derivatives are hypoglycemic drugs used for the treatment of diabetes. However, they can also be used as a stopper in horseracing. This paper describes a convenient method for the separation and simultaneous detection of 10 anti-diabetic drugs (namely glipizide, glibenclamide, glimepiride, gliclazide, tolazamide, tolbutamide, nateglinide, repaglinide, rosiglitazone and pioglitazone) in equine plasma and urine by LC-MS-MS. Methods: The anti-diabetics were isolated from equine plasma and urine by liquid-liquid extraction with 1,2-dichloro...
Grimmer NM, Gimbar RP, Bursua A, Patel M.The literature regarding rhabdomyolysis secondary to illicit drug use is sparse. Clenbuterol is a bronchodilator approved for veterinary use, which in high doses can increase protein deposition and lipolysis similarly to anabolic steroids, and is thereby abused for bodybuilding and weight loss effects. Clenbuterol has previously been described in case reports to be cardiotoxic, with patient presentations similar to overdoses of sympathomimetic substances, but reports of rhabdomyolysis are limited to a single case series in horses. Methods: We report the first case of rhabdomyolysis secondary t...
van der Kolk JH, Wijnberg ID, Westermann CM, Dorland L, de Sain-van der Velden MG, Kranenburg LC, Duran M, Dijkstra JA, van der Lugt JJ, Wanders RJ....This case-series describes fourteen horses suspected of equine acquired multiple acyl-CoA dehydrogenase deficiency (MADD) also known as atypical myopathy of which seven cases were confirmed biochemically with all horses having had access to leaves of the Maple tree (Acer pseudoplatanus) covered with European tar spot (Rhytisma acerinum). Assessment of organic acids, glycine conjugates, and acylcarnitines in urine was regarded as gold standard in the biochemical diagnosis of equine acquired multiple acyl-CoA dehydrogenase deficiency.
Womble AY, Giguère S, Lee EA, Vickroy TW.To determine pharmacokinetics of clarithromycin and concentrations in body fluids and bronchoalveolar (BAL) cells of foals. Methods: 6 healthy 2-to 3-week-old foals. Methods: In a crossover design, clarithromycin (7.5 mg/kg) was administered to each foal via IV and intragastric (IG) routes. After the initial IG administration, 5 additional doses were administered IG at 12-hour intervals. Concentrations of clarithromycin and its 14-hydroxy metabolite were measured in serum by use of high-performance liquid chromatography. A microbiologic assay was used to measure clarithromycin activity in seru...
Burgess EC.Blood samples from Wisconsin horses and cows suspected of having clinical disease due to Borrelia burgdorferi infection were submitted by veterinary practitioners. All serum, milk, colostrum, and synovial samples were tested for B. burgdorferi antibodies by immunofluorescence. Whole blood, milk, colostrum, and synovial fluid samples were cultured for B. burgdorferi. Records were kept on the clinical signs of antibody-positive animals, date of sample, and location of the animal by county. Of the samples tested for antibodies 282/430 cow sera, 118/190 horse sera, 5/10 cow synovial fluids, 3/6 ho...
Būda V, Mozūraitis R, Kutra J, Borg-Karlson AK.Previously it was shown that m- and p-cresols in the urine of mares exhibits a temporally reproducible pattern that is dependent on ovarian activity and, thus, provides information about the timing of ovulation. New behavioral data demonstrate 1) that stallions spend significantly more time sniffing p-cresol as compared to o-, and m-cresols, and, 2) that the extent of stallions' erections differ significantly in response to different types of samples. The lowest erection level was recorded for the pure-water control, a moderate erection level was elicited by the urine of diestrous mares, and t...
Weidolf LO, Lee ED, Henion JD.Sulfoconjugated anabolic steroids were separated by micro-bore high-performance liquid chromatography. The eluent was introduced into the atmospheric pressure ion source of the triple-quadrupole mass spectrometer via an ion spray liquid chromatograph/mass spectrometer interface operated in the negative ion mode. The limit of detection was 10 pg on-column by selected ion monitoring of the molecular ion and the response increased linearly over a concentration range of 2.4 orders of magnitude. Following work-up by a liquid-solid extraction procedure of equine urine samples, full-scan daughter ion...
Mozūraitis R, Būda V, Kutra J, Borg-Karlson AK.Urine samples from 14 mares, belonging to five breeds, were collected at estrus and diestrus to search for estrous specific volatile compounds which could be used to determine ovulation time. Around 150 volatiles were collected from urine head-space samples by solid phase micro extraction technique, and analyses were conducted by gas chromatography-mass spectrometry methods. Comparison of chromatographic profiles of volatile substances revealed that concentrations of m- and p-cresols were significantly greater during estrus while diethylphthalate was more abundant at diestrus. Monitoring of m-...
Fragkaki AG, Kioukia-Fougia N, Kiousi P, Kioussi M, Tsivou M.The artificial increase of the physical capability of horses using drugs is well known in racing and other equine sports. Both illicit and therapeutic substances are regarded as prohibited substances in competition in most countries. Some countries make distinctions for a few, specific drugs which are, however, allowed for use in other countries. The primary objective in the case of doping control is the detection of any trace of drug exposure, either parent drug or any of its metabolites, using the most powerful analytical methods which are generally based on chromatographic/mass spectrometri...
Dowling PM, Wilson RC, Tyler JW, Duran SH.The pharmacokinetics of ciprofloxacin was investigated in healthy, mature ponies. Ciprofloxacin was administered intravenously to six ponies at a dose of 5 mg per kg body weight. Seven days later, ciprofloxacin was administered orally to each pony at the same dose. Intravenous ciprofloxacin concentration vs. time data best fit a two-compartment open model with first-order elimination from the central compartment. Mean plasma half-life, based on the terminal phase, was 157.89 min (harmonic mean). Total body clearance of ciprofloxacin was 18.12 +/- 3.99 mL/min/kg. Volume of distribution at stead...
Knych HK, Vidal MA, Casbeer HC, McKemie DS.The use of triamcinolone acetonide (TA) in performance horses necessitates establishing appropriate withdrawal times prior to performance. Objective: To describe the plasma pharmacokinetics of TA and time-related urine and synovial fluid concentrations following i.m. and intra-articular administration to exercised Thoroughbred horses. Methods: Block design. Methods: Twelve racing fit adult Thoroughbred horses received a single i.m. administration of TA (0.1 mg/kg bwt). After an appropriate washout period, the same horses then received a single intra-articular TA administration (9 mg) into the ...
Morgan RA, Keen JA, Homer N, Nixon M, McKinnon-Garvin AM, Moses-Williams JA, Davis SR, Hadoke PWF, Walker BR.Equine Cushing disease [pituitary pars intermedia dysfunction (PPID)] is a common condition of older horses, but its pathophysiology is complex and poorly understood. In contrast to pituitary-dependent hyperadrenocorticism in other species, PPID is characterized by elevated plasma ACTH but not elevated plasma cortisol. In this study, we address this paradox and the hypothesis that PPID is a syndrome of ACTH excess in which there is dysregulation of peripheral glucocorticoid metabolism and binding. In 14 horses with PPID compared with 15 healthy controls, we show that in plasma, cortisol levels...
Hamond C, Martins G, Bremont S, Medeiros MA, Bourhy P, Lilenbaum W.A strain of Leptospira kirschneri (serogroup Grippotyphosa) was cultured from urine of a mare post-abortion in Brazil and characterized by serogrouping, multiple-locus variable-number tandem repeat analysis, PGFE, and sequencing of genes rrs and secY. Strains of L. kirschneri have apparently never been recovered from horses in tropical area, only in Europe and USA. Knowledge of local epidemiology is important to interpret genetic profiles of leptospires circulating in an area.
Zeyner A, Romanowski K, Vernunft A, Harris P, Müller AM, Wolf C, Kienzle E.The provision of NaCl, according to current recommendations, to horses in moderate work has been shown to induce immediate postprandial acidosis. The present study aimed to clarify whether this NaCl induced acidosis i) persists beyond the immediate postprandial period, and ii) is still present after a 2 week adaptation period. Six adult warmblood mares in moderate work received daily 1.00 kg hay per 100 kg body weight (bwt) only together with 0.64 kg unprocessed cereal grains/100 kg bwt.d as fed basis. Using a 3x3 Latin Square, either 0 (NaCl-0), 50 (NaCl-50) or 100 (NaCl-100) g NaCl/d were fe...
Morresey PR, Mackay RJ.To measure serum polymyxin B concentration after single and repeated IV infusions in horses. Methods: 5 healthy horses. Methods: In study 1, 1 mg (6,000 U) of polymyxin B/kg was given IV and blood samples were collected for 24 hours. In study 2, 1 mg of polymyxin B/kg was given IV every 8 hours for 5 treatments and blood samples were collected until 24 hours after the last dose. Polymyxin B concentration was measured as the ability to suppress nitrite production by murine macrophages stimulated with lipopolysaccharide and interferon-alpha. Urine was collected prior to the first drug infusion a...
McCornico RS, Duckett WM, Wood PA.Persistent hyperammonemia was diagnosed in 2 Morgan fillies with clinical signs that developed early in the postweaning period. Diagnostic evaluation, including routine serum chemistries, CBC, liver biopsy, hepatic ultrasonography, liver function test, and necropsy findings did not support a toxic, developmental, or infectious cause. Abnormal serum amino acid and urine orotic acid concentrations suggest that the foals may have had an inherited disorders described in humans as hyperornithinemia, hyperammonemia, and homocitrullinuria (HHH) syndrome. The disorder is thought to be caused by a defe...
