The topic of drugs and horses encompasses the study of various pharmacological agents used in equine medicine for therapeutic purposes. This includes the administration of medications for pain management, disease treatment, and performance enhancement. The pharmacokinetics and pharmacodynamics of drugs in horses are key areas of research, as they determine the absorption, distribution, metabolism, and excretion of these substances. Additionally, the topic covers the detection and regulation of substances in competitive equestrian sports to ensure fair play and animal welfare. This page compiles peer-reviewed research studies and scholarly articles that explore the effects, safety, and regulatory aspects of drug use in equine health and performance.
Lorenzo-Figueras M, Merritt AM.To measure plasma cholecystokinin (CCK) activity and the effect of a CCK-1 receptor antagonist on accommodation of the proximal portion of the stomach, and subsequent gastric emptying, in horses after ingestion of high-fat or high-carbohydrate meals. Methods: 6 healthy adult horses with gastric cannulas. Methods: In the first study, horses were offered a high-fat (8% fat) or a high-carbohydrate (3% fat) pelleted meal of identical volume, caloric density, and protein content. Related plasma CCK-like activity was measured by radioimmunoassay (RIA). In a separate experiment, a horse was fed a gra...
Houghton E, Teale P, Dumasia MC.For almost two decades we have known that enzymatic hydrolysis of "normal" urine samples from the entire male horse using Escherichia coli (E. coli) followed by solvolysis (ethyl acetate:methanol:sulphuric acid) results in the detection of significant amounts of estr-4-ene-3,17-dione (19-norandrost-4-ene-3,17-dione) along with estr-4-en-17beta-ol-3-one (19-nortestosterone, nandrolone) in extracts of the hydrolysed urine and that both steroids are isolated from the solvolysis fraction. This solvolysis process is targeted at the steroid sulphates. Also we have shown that 19-norandrost-4-ene-3,17...
Camargo FC, Robinson NE, Berney C, Eberhart S, Baker S, DeTolve P, Derksen FJ, Harkins JD, Lehner AF, Tobin T.Trimetoquinol (TMQ) is a potent beta-adrenoceptor agonist bronchodilator used in human medicine but has not been evaluated for potential use as a therapeutic agent for horses with 'heaves'. Objective: To assess the pharmacodynamics of TMQ in horses with 'heaves' to determine potential therapeutic effects. Methods: Increasing doses of TMQ were administered to horses with 'heaves' by i.v. and intratracheal (i.t.) routes. Doses ranged 0.001-0.2 microg/kg bwt i.v. and 0.01-2 microg/kg bwt i.t. Cardiac and airways effects were assessed by measurement of heart rate (HR) and maximal change in pleural...
Slocombe JO, Heine J, Barutzki D, Slacek B.The aim of this study with horses and a few ponies naturally infected with tapeworms was to confirm in clinical trials the efficacy and safety of a praziquantel horse paste 9%. The field trials were conducted in 1997 and 1998 in Canada, France, Germany and New Zealand. A secondary aim of the study in Canada was to determine if a 24h post-treatment fecal sample provides the best estimate of the prevalence of tapeworms in horses when using a fecal examination technique. Fecal samples were taken from each of 1062 animals at least three times pre-treatment (PRT). In Canada, fecal samples were exam...
Stanley SM, Wee WK, Lim BH, Foo HC.Direct-injection LC-LC hybrid tandem MS methods have been developed for undertaking broad-based screening for acidic drugs in protein-precipitated plasma and neutral doping agents in equine urine. In both analyses, analytes present in the matrix were trapped using a HLB extraction column before being refocused and separated on a Chromolith RP-18e monolithic analytical column using a controlled differential gradient generated by proportional dilution of the first column's eluent with water. Each method has been optimised by the adoption of a mobile phase and gradient that was tailored to enhanc...
Milligan M, Kukanich B, Beard W, Waxman S.Lidocaine is administered as an intravenous infusion to horses for a variety of reasons, but no study has assessed plasma lidocaine concentrations during a 12-h infusion to horses. The purpose of this study was to evaluate the plasma concentrations and pharmacokinetics of lidocaine during a 12-h infusion to postoperative horses. A second purpose of the study was to evaluate the in vitro plasma protein binding of lidocaine in equine plasma. Lidocaine hydrochloride was administered as a loading dose, 1.3 mg/kg over 15 min, then by a constant rate IV infusion, 50 microg/kg/min to six postoperativ...
Orsini JA, Moate PJ, Kuersten K, Soma LR, Boston RC.The safety and pharmacokinetics of fentanyl, delivered transdermally at a dosage of 60-67 microg/kg, were investigated in six healthy adult horses. Three transdermal fentanyl patches (Duragesic), each containing 10 mg of fentanyl citrate, were applied to the mid-dorsal thorax of each horse and left in place for 72 h. Plasma fentanyl concentrations were periodically measured throughout this period and for 12 h after patch removal. After an initial delay of approximately 2 h, the plasma fentanyl concentration rose rapidly in a fairly linear fashion, reaching a peak at around 12 h; thereafter, it...
Leung GN, Leung DK, Wan TS, Wong CH.This paper describes a high throughput LC-MS-MS method for the screening of 75 basic drugs in equine plasma at sub-ppb levels. The test scope covers diversified classes of drugs including some alpha- and beta-blockers, alpha- and beta-agonists, antihypotensives, antihypertensives, analgesics, antiarrhythmics, antidepressants, antidiabetics, antipsychotics, antiulcers, anxiolytics, bronchodilators, CNS stimulants, decongestants, sedatives, tranquilizers and vasodilators. A plasma sample was first deproteinated by addition of trichloroacetic acid. Basic drugs were then extracted by solid-phase e...
Mills PC, Cross SE.An increasing number of formulations are applied to equine skin, yet variable penetration can affect efficacy, or the incidence of adverse effects, or both. To investigate the effects of common methods of skin preparation on transdermal drug penetration in vitro, we clipped, harvested, and froze skin samples from 5 Thoroughbred geldings. Thawed samples were prepared as follows: control (no preparation); cleaned with aqueous chlorhexidine (Aq-C, 0.1% w/v); cleaned with alcoholic chlorhexidine (Al-C, 0.5% w/v); shaved (Sh); or tape-stripped (Ta) with the use of adhesive tape. The samples were th...
Colas C, Garcia P, Popot MA, Bonnaire Y, Bouchonnet S.A method has been developed for the analysis and characterization in equine urine and plasma of iridoid glycosides: harpagide, harpagoside and 8-para-coumaroyl harpagide, which are the main active principles of Harpagophytum, a plant with antiinflammatory properties. The method involves liquid chromatography coupled with positive electrospray ionization mass spectrometry. The addition of sodium or lithium chloride instead of formic acid in the eluting solvent has been studied in order to enhance the signal and to modify the ion's internal energy. Fragmentation pathways and associated patterns ...
Davis E, Rush BR, Herr LG, Ewert KM.Successful clinical management of bacterial pneumonia in horses depends on the administration of an appropriate antimicrobial agent at an adequate dosage and frequency, given by the correct route of administration for an adequate duration. Empiric antimicrobial therapy should be based on the clinician's experience and current veterinary literature. Based on the frequency of Gram-positive bacterial pathogens isolated from horses with bacterial pneumonia, every effort should be made to provide antimicrobial coverage for this class of pathogens. Gram-negative pathogens may co-exist; therefore, br...
Luo T, Bertone JJ, Greene HM, Wickler SJ.In its FDA approved formulation, N-butylscopolammonium bromide (Buscopan Injectable Solution, Boehringer Ingelheim Vetmedica) is an anticholinergic spasmolytic agent indicated for management of abdominal pain associated with spasmodic colic, flatulent colic, and simple impactions in horses. Use of this drug ablates gastrointestinal peristalsis and rectal pressure. It ahs been suggested that N-butylscopolammonium bromide could be used to facilitate rectal examinations in horses. This study compared the effects of N-butylscopolammonium bromide versus lidocaine and a saline control on rectal pres...
Parra-Sanchez A, Lugo J, Boothe DM, Gaughan EM, Hanson RR, Duran S, Belknap JK.To evaluate the pharmacokinetic-pharmacodynamic parameters of enrofloxacin and a low dose of amikacin administered via regional IV limb perfusion (RILP) in standing horses. Methods: 14 adult horses. Methods: Standing horses (7 horses/group) received either enrofloxacin (1.5 mg/kg) or amikacin (250 mg) via RILP (involving tourniquet application) in 1 forelimb. Samples of interstitial fluid (collected via implanted capillary ultrafiltration devices) from the bone marrow (BMIF) of the third metacarpal bone and overlying subcutaneous tissues (STIF), blood, and synovial fluid of the radiocarpal joi...
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...
Ho EN, Kwok WH, Leung DK, Wan TS, Wong AS.Turinabol (4-chloro-17alpha-methyl-17beta-hydroxy-1,4-androstadien-3-one) is a synthetic oral anabolic androgenic steroid. As in the case of other anabolic steroids, it is a prohibited substance in equine sports. The metabolism of turinabol in human has been reported previously; however, little is known about its metabolic fate in horses. This paper describes the studies of both the in vitro and in vivo metabolism of turinabol in racehorses with an objective to identify the most appropriate target metabolites for detecting turinabol administration. For the in vitro studies, turinabol was incub...
Roelfstra L, Betschart B, Pfister K.In a study on the seasonal dynamics of the gastro-intestinal nematode egg production in horses, one breeding farm also revealed a particularly high prevalence of Anoplocephala spp. infection. Consequently, this farm was chosen for analysing the seasonal pattern of the tapeworm egg excretion over a one year period in order to establish the most favourable periods for an appropriate and successful cestocidal treatment. The seasonal analysis showed a significantly higher (p < 0.05) Anoplocephala spp. egg excretion between July and October, i.e. during the second part of the grazing period. This r...
Mills PC, Cross SE.The rate and regional differences for the penetration of fentanyl through equine skin was investigated in vitro using a commercial transdermal therapeutic system (TTS) or 'patch'. Skin collected from the thorax, groin and leg (dorsal metacarpal) regions of five horses was placed in diffusion cells and a fentanyl TTS applied to each skin sample. Drug penetration through each skin sample over 48 h measured using high performance liquid chromatography (HPLC). Cumulative penetration (microg/cm2) was plotted against time (h) and used to regress the steady state flux (microg/cm2/h) of fentanyl throu...
Lyons ET, Tolliver SC, Rathgeber RA, Collins SS.Foals (79), born in 2004 on three thoroughbred horse farms (C, M, and S) in central Kentucky, were fed pyrantel tartrate daily, beginning at about 3 months of age. In addition, other parasiticides [fenbendazole (FBZ), ivermectin (IVM) alone or with praziquantel (PRAZ), oxibendazole (OBZ), pyrantel pamoate (PRT), and moxidectin (MOX)] were given periodically. All treatments were administered by farm personnel. Over a 14-month period, from May 2004 to July 2005, collections (n=989) of feces were made from the foals for determination of presence of internal parasite eggs/oocysts by qualitative an...
Russo AT, White MA, Watowich SJ.Alphavirus replication and propagation is dependent on the protease activity of the viral nsP2 protein, which cleaves the nsP1234 polyprotein replication complex into functional components. Thus, nsP2 is an attractive target for drug discovery efforts to combat highly pathogenic alphaviruses. Unfortunately, antiviral development has been hampered by a lack of structural information for the nsP2 protease. Here, we report the crystal structure of the nsP2 protease (nsP2pro) from Venezuelan equine encephalitis alphavirus determined at 2.45 A resolution. The protease structure consists of two dist...
Davis JL, Little D, Blikslager AT, Papich MG.Ussing chambers have been used to study the mucosal permeability of drugs in humans, rats and other species. This data can then be used to develop in vitro/in vivo correlations (IVIVC) for drugs based on the Biopharmaceutics Classification System (BCS). Due to the poor oral bioavailability of many drugs in the horse, this method may be useful for screening drugs before development to determine if they warrant further study. Cephalexin (CPX), marbofloxacin (MAR), metronidazole (MTZ) and fluconazole (FCZ) were chosen for this study based on the wide range of physicochemical properties and bioava...
Peyrou M, Bousquet-Melou A, Laroute V, Vrins A, Doucet MY.Enrofloxacin and marbofloxacin are two veterinary fluoroquinolones used to treat severe bacterial infections in horses. A repeated measures study has been designed to compare their pharmacokinetic parameters, to investigate their bioavailability and to estimate their absorbed fraction and first-pass effect by using plasma, urinary and metabolite data collected from five healthy mares. Clearance and V(d(ss)) were greater for enrofloxacin (mean +/- SD = 6.34 +/- 1.5 mL/min/kg and 2.32 +/- 0.32 L/kg, respectively) than for marbofloxacin (4.62 +/- 0.67 mL/min/kg and 1.6 +/- 0.25 L/kg, respectively...
Oku K, Ohta M, Katoh T, Moriyama H, Kusano K, Fujinaga T.We examined the influence of propofol infusion on cardiovascular system at the rate of 0.14, 0.20 and 0.30 mg/kg/min in six adult Thoroughbred horses. The cardiovascular parameters were heart rate (HR), mean arterial pressure (MAP), mean right atrial pressure (MRAP), stroke volume (SV), cardiac output (CO), systemic vascular resistance (SVR), pre-ejection period (PEP) and ejection time (ET). In order to keep the ventilation conditions constantly, intermittent positive pressure ventilation was performed, and the partial arterial CO(2) pressure was maintained at 45 to 55 mmHg during maintenance ...
Boscan P, Steffey EP, Farver TB, Mama KR, Huang NJ, Harris SB.To compare anesthesia-related events associated with IV administration of 2 novel micellar microemulsion preparations (1% and 5%) and a commercially available formulation (1%) of propofol in horses. Animals-9 healthy horses. Methods: On 3 occasions, each horse was anesthetized with 1 of the 3 propofol formulations (1% or 5% microemulsion or 1% commercial preparation). All horses received xylazine (1 mg/kg, IV), and anesthesia was induced with propofol (2 mg/kg, IV). Induction and recovery events were quantitatively and qualitatively assessed. Venous blood samples were obtained before and at in...
Ivester KM, Adams SB, Moore GE, Van Sickle DC, Lescun TB.To determine synovial fluid gentamicin concentrations and evaluate adverse effects on the synovial membrane and articular cartilage of tarsocrural joints after implantation of a gentamicin-impregnated collagen sponge. Methods: 6 healthy adult mares. Methods: A purified bovine type I collagen sponge impregnated with 130 mg of gentamicin was implanted in the plantarolateral pouch of 1 tarsocrural joint of each horse, with the contralateral joint used as a sham-operated control joint. Gentamicin concentrations in synovial fluid and serum were determined for 120 hours after implantation by use of ...
Eysker M, van Doorn DC, Lems SN, Weteling A, Ploeger HW.Due to excessive and inappropriate use of dewormers anthelmintic resistance has developed as a significant problem in horse parasites in the Netherlands. Since it is unlikely that new classes of anthelmintics against horse nematodes will be introduced in the near future, it is important to use the present drugs wisely. Veterinarians should advice horse owners about worm control programs with a more targeted approach. The number of anthelmintic treatments should be reduced and, through selective anthelmintic treatments, further development of anthelmintic resistance should be delayed. Preferabl...
Dirikolu L, McFadden ET, Ely KJ, ElkHoly H, Lehner AF, Thompson K.Clonidine is classified as a class 3 performance-enhancing agent by the Association of Racing Commissioners International and thus has the potential to influence the outcome of a race. In this study, the authors developed and validated a sensitive gas chromatograph and mass spectrometer method to determine the pharmacokinetic parameters of clonidine in equine plasma samples after IV administration of a single dose (0.025 mg/kg) of clonidine in horses. At this dose, clonidine produced rapid and profound sedation, which cold be quickly reversed with yohimbine. Clonidine was able to produce an an...
Fernández-Varón E, Ayala I, Marín P, Carrión A, Martos N, Escudero E, Cárceles CM.Danofloxacin is a fluoroquinolone developed for veterinary medicine showing an excellent activity. However, danofloxacin pharmacokinetics profile have not been studied in horses previously. Objective: To study the pharmacokinetics following i.v., i.m. and intragastric (i.g.) administration of 1.25 mg/kg bwt danofloxacin to 6 healthy horses. Methods: A cross-over design was used in 3 phases (2 x 2 x 2), with 2 washout periods of 15 days (n = 6). Danofloxacin (18%) was administered by i.v. and i.m. routes at single doses of 1.25 mg/kg bwt. For i.g. administration an oral solution was prepared an...
Stokes AM, Venugopal CS, Hosgood G, Eades SC, Moore RM.The goals of this study were to determine the concentration-response (C-R) relationship of endothelin-1 (ET-1), compare 2 ET-receptor antagonists and determine the antagonist concentrations that block the vasomotor effects of ET-1, and compare the effectiveness of ET-1 and previously studied vasoconstrictors in equine palmar digital arterial and venous rings in vitro. Vessel rings from 8 nonlaminitic horses were placed in Tyrode's solution, 1 side fixed to the floor of an organ bath and the other side fixed to a force-displacement transducer. Two separate studies were conducted: (I) incubation...
Sabaté D, Homedes J, Salichs M, Sust M, Monreal L.In horses, it has been demonstrated that suxibuzone (SBZ) has a lower gastric ulcerogenic effect than phenylbutazone (PBZ). However, no field trials have been reported comparing the efficacy of the drugs in alleviating lameness. Objective: To compare the therapeutic effect of SBZ to that of PBZ when administered orally in lame horses. Acceptability of both products was also compared. Methods: Lame horses (n = 155) were used in a multicentre, controlled, randomised and double-blinded clinical trial. Horses were treated orally with either SBZ or PBZ at equivalent therapeutic dosages. PBZ was giv...
McReynolds CB, Yang J, Guedes A, Morisseau C, Garcia R, Knych H, Tearney C, Hamamoto B, Hwang SH, Wagner K, Hammock BD.There are few novel therapeutic options available for companion animals, and medications rely heavily on repurposed drugs developed for other species. Considering the diversity of species and breeds in companion animal medicine, comprehensive PK exposures in the companion animal patient is often lacking. The purpose of this paper was to assess the pharmacokinetics after oral and intravenous dosing in domesticated animal species (dogs, cats, and horses) of a novel soluble epoxide hydrolase inhibitor, EC1728, being developed for the treatment of pain in animals. Results: Intravenous and oral adm...
Galbraith EA, McKellar QA.Flunixin was highly protein bound in the serum of dogs (92.2 per cent), goats (84.8 per cent) and horses (86.9 per cent). Meclofenamic acid was also highly protein bound, although there were larger differences between the extent of the binding in dogs (90.3 per cent), goats (84.7 per cent) and horses (99.8 per cent). Both flunixin and meclofenamic acid were potent inhibitors of the in vitro generation of thromboxane (Tx) B2 in blood. Flunixin inhibited the generation of TxB2 by 50 per cent of the maximum response (IC50) in dog, goat and horse blood at concentrations of 0.10, 0.02 and 0.04 micr...
Diez Bernal S, Studer N, Thormann W, Spadavecchia C, Levionnois O.To evaluate the effect of a romifidine infusion on antinociception and sedation, and to investigate its relationship with plasma concentration. Methods: Prospective, experimental, nonrandomized trial. Methods: A total of 10 healthy adult warmblood horses. Methods: Romifidine (loading dose: 0.08 mg kg, infusion: 0.03 mg kg hour) was administered intravenously over 120 minutes. Romifidine plasma concentrations were determined by capillary electrophoresis. Sedation quality and nociceptive thresholds were evaluated at regular time points before, during and after romifidine administration. The noci...
Brütsch DR, Hunziker P, Pot S, Tappeiner C, Voelter K.Intraocular fibrin clots caused by severe uveitis can be a sight-threatening condition that needs to be resolved quickly and reliably. Intracameral injection of tissue-plasminogen activator (tPA) is commonly used to resolve intraocular fibrin. However, the drug does not reach fibrinolytic concentrations after topical application. Desmoteplase (DSPA) is a structurally similar but smaller fibrinolytic agent with a higher fibrin selectivity, a longer half-life, and better biocompatibility compared with tPA. This study was designed to evaluate the corneal and scleral permeability of DSPA in rabbit...
Frey LP, Kline KH, Foreman JH.Analysis of data collected at racetracks showed that temperature, the diuretic drug, frusemide, exercise, temperature/exercise interaction and sex/age had significant (P < 0.05) effects on pH and bicarbonate ion concentration (P < 0.01). Sodium concentrations were significantly (P < 0.001) affected by temperature and frusemide. We suggest that the normal range limits for blood sodium, bicarbonate and pH used in prerace testing procedures should be adjusted for ambient temperature and for horses given frusemide and/or prerace exercise. These adjustments should improve the precision of ...
Hubbell JA, Sams RA, Schmall LM, Robertson JT, Hinchcliff KW, Muir WW.Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. Objective: To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. Methods: Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, h...
Shibany KA, Pratt SL, Aldurdunji M, Totemeyer S, Paine SW.Horses are exposed to various kinds of medication, however, there are limited determinations of plasma clearance (CL) for the drugs used due to the high cost of equine studies.Many of the CL values generated come from the equine sports industry for determining drug plasma screening limits in the control of medications at the time of competition.The kinetics of omeprazole metabolism were investigated in freshly isolated and cryopreserved equine hepatocytes and hepatic microsomes ( = 3 horses).The V, K and intrinsic clearance (CL) of omeprazole were determined via the substrate depletion me...
Snow DH, Baxter P, Whiting B.The pharmacokinetics of meclofenamic acid were studied in Thoroughbred horses and in ponies. After intravenous (i.v.) administration of either 2 mg/kg or 4 mg/kg sodium meclofenamate the elimination half-life was of the order of 0.9 h while the volume of distribution was found to be 0.128 litre/kg. Elimination was in accordance with a one-compartment model. Following oral administration of either meclofenamic acid (4 mg/kg) or sodium meclofenamate (4 mg/kg) a much longer terminal half-life than that calculated for Kel from i.v. data was found. This anomaly indicated that the 'flip-flop' phenom...
Jernigan AD, Wilson RC, Booth NH, Hatch RC, Akbari A.In steers, horses and dogs, the comparative pharmacokinetics of yohimbine were determined using model-independent analysis. The intravenous dose of yohimbine was 0.25 mg/kg of body weight in steers, 0.075 or 0.15 mg/kg in horses, and 0.4 mg/kg in dogs. The mean residence time (+/- SD) of yohimbine was 86.7 +/- 46.2 min in steers, 106.2 +/- 72.1 to 118.7 +/- 35.0 min in horses, and 163.6 +/- 49.7 min in dogs. The mean apparent volume of distribution of yohimbine at steady state was 4.9 +/- 1.4 L/kg for steers, 2.7 +/- 1.0 to 4.6 +/- 1.9 L/kg for horses, and 4.5 +/- 1.8 L/kg for dogs. The total ...
Drudge JH, Lyons ET, Tolliver SC, Kubis JE.The efficacy of oxibendazole given at dose level of 10 mg/kg of body weight was determined by 10 critical tests in foals and by 2 clinical trials in 20 foals (16 treated, 4 nontreated), with special interest in the drug activity against Parascaris equorum. The drug was uniformly efficacious (100%) against P equorum in the 10 critical-test foals, each having between 22 and 236 ascarids. Posttreatment reductions of ascarid egg counts in fecal samples were also 100% in suckling foals treated with oxibendazole given as a drench. Ascarid eggs did not reappear in fecal samples until the 8th week aft...
Brink P, DeGraves F, Ravis WR, Johansen D, Campbell JD, Duran SH.To determine intravascular and intrasynovial pharmacokinetics of the R and S enantiomers of ketoprofen after i.v. and i.m. administration to horses. Methods: 6 healthy adult mares. Methods: Horses were weighed and ketoprofen (2.2 mg/kg of body weight) was administered i.v. Blood and synovial fluid samples were obtained and analyzed for concentrations of the R and S enantiomers by means of a modified reverse-phase stereospecific high-pressure liquid chromatographic method. Three weeks later, the procedure was repeated, except that ketoprofen was given IM. Protein binding of ketoprofen enantiome...
Cokelaere SM, Groen WMGAC, Plomp SGM, de Grauw JC, van Midwoud PM, Weinans HH, van de Lest CHA, Tryfonidou MA, van Weeren PR, Korthagen NM.There is an increasing interest in controlled release systems for local therapy in the treatment of human and equine joint diseases, aiming for optimal intra-articular concentrations with no systemic side effects. In this study, the intra-articular tolerability and suitability for local and sustained release of tacrolimus (FK506) from monospheres composed of [PDLA-PEG1000]-b-PLLA multiblock copolymers were investigated. Unloaded and tacrolimus-loaded (18.4 mg tacrolimus/joint) monospheres were injected into the joints of six healthy horses, with saline and hyaluronic acid (HA) in the contralat...
This work proposes an application of a minimal complexity physiologically based pharmacokinetic model to predict tramadol concentration vs time profiles in horses. Tramadol is an opioid analgesic also used for veterinary treatments. Researchers and medical doctors can profit from the application of mathematical models as supporting tools to optimize the pharmacological treatment of animal species. The proposed model is based on physiology but adopts the minimal compartmental architecture necessary to describe the experimental data. The model features a system of ordinary differential equations...
Teale P, Houghton E.The fight against doping in sport using analytical chemistry is a mature area with a history of approximately 100 years in horseracing. In common with human sport, anabolic/androgenic steroids (AASs) are an important group of potential doping agents. Particular issues with their detection are extensive metabolism including both phase I and phase II. A number of the common AASs are also endogenous to the equine. A further issue is the large number of synthetic steroids produced as pharmaceutical products or as 'designer' drugs intended to avoid detection or for the human supplement market. An u...
Stick JA, Chou CC, Derksen FJ, Arden WA.Isolated jejunal segments were perfused at a constant blood flow rate to determine simultaneously the effects of xylazine on intestinal vascular resistance, motility, compliance, and oxygen consumption in 12 anesthetized ponies. Xylazine was infused into the artery perfusing the intestinal segment (group 1), or into the jugular vein as a single IV bolus (group 2), or 3 times as IV boluses repeated at 10-minute intervals (group 3). Dose-response curves in group 1 indicated a biphasic response to the drug with vasoconstriction, increased motility, and increased oxygen consumption at lower doses ...
Waraksa E, Woźniak MK, Kłodzińska E, Wrzesień R, Bobrowska-Korczak B, Namieśnik J.Ibuprofen is widely used in human and veterinary medicine for the treatment of chronic pain as well as rheumatic and musculoskeletal disorders. However, the analgesic and anti-inflammatory properties of Ibuprofen have contributed to frequent drug abuse in equestrian sports. A sensitive and rapid gas chromatography with tandem mass spectrometry based method with a simple liquid-liquid extraction and derivatization requiring 200 μL volume of sample and 2 mL of extraction solvent for the simultaneous determination of ibuprofen and its metabolites was developed. The proposed procedure was optim...
Waller CC, Weththasinghe SA, McClure L, Cawley AT, Suann C, Suann E, Sutherland E, Cooper E, Heather A, McLeod MD.Hemapolin (2α,3α-epithio-17α-methyl-5α-androstan-17β-ol) is a designer steroid that is an ingredient in several "dietary" and "nutritional" supplements available online. As an unusual chemical modification to the steroid A-ring could allow this compound to pass through antidoping screens undetected, the metabolism of hemapolin was investigated by an in vivo equine drug administration study coupled with GC-MS analysis. Following administration of synthetically prepared hemapolin to a thoroughbred horse, madol (17α-methyl-5α-androst-2-en-17β-ol), reduced and dihydroxylated madol (17α-me...
Knych HK, Vale A, Wilson WD, Kass PH, Arthur RM, Jones JH.Furosemide is a diuretic agent used commonly in racehorses to attenuate the bleeding associated with exercise-induced pulmonary hemorrhage (EIPH). The current study describes serum and urine concentrations and the pharmacokinetics of furosemide following administration at 4 and 24 hrs prior to maximal exercise. Eight exercised adult Thoroughbred horses received a single IV administration of 250 mg of furosemide at 4 and 24 hrs prior to maximal exercise on a high-speed treadmill. Blood and urine samples were collected at time 0 and at various times for up to 72 hrs and furosemide concentrat...
Moss M S..A review of positive Jockey Club "dope tests" during the 12 years from 1970 to 1981 inclusive is presented and a comparison made with certain overseas racing authorities for varying periods between 1975 and 1981. Urinary pH of post race urine samples is predominantly acidic (although varying in a significant manner throughout the year) and thus favours excretion of the generally more potent basic drugs. The proportion of positive results was about the same in winners and non-winners, ie, one in 400 horses sampled. Drugs found fell mainly into four categories: methylxanthines; non-steroidal ant...
Marsh AE, Mullins AL, Lakritz J.Parasite-specific incorporation of (3)H-uracil was used to assess the replication of Sarcocystis neurona, a protozoal parasite associated with equine protozoal myeloencephalitis (EPM). Anti-protozoal drugs, pyrimethamine (0.01, 0.1 and 1.0microg/ml PYR), sulfadiazine (5microg/ml; SDZ), sulfamethoxazole (5microg/ml; SMZ), diclazuril (100ng/ml; DCZ), atovaquone (0.04ng/ml; ATQ), tetracycline (5microg/ml; TET) and the herbicide glyphosate (1.5 and 4.5mM; GLY) were studied with varying S. neurona parasite densities (2x10(1)-1.2x10(6)merozoites/well). A microtiter plate format was used to test thes...
Whittem T, Firth EC, Hodge H, Turner K.This study examined the pharmacokinetics of steady-state phenylbutazone and single bolus intravenous gentamicin when administered together in the horse. The trial design was completed as a cross-over with seven thoroughbred horses. In the first phase each horse received 2.2 mg/kg gentamicin intravenously. After a 2-week washout, each horse received 4.4 mg/kg phenylbutazone intravenously every 24 h for 5 days. On the fourth day each horse received gentamicin as before. Plasma was harvested for gentamicin concentration determination by fluorescence polarization immunoassay and for phenylbutazone...
Moorman VJ, Bass L, King MR.To determine the effects of 3 α2-adrenergic receptor agonists (α2-ARAs), alone or in combination with butorphanol tartrate, on objective measurements of lameness in horses. Methods: 17 adult polo horses with naturally occurring forelimb or hind limb lameness (or both). Methods: In a crossover design, each horse received each protocol (saline [0.09% NaCl] solution [2 mL, IV] or xylazine hydrochloride [0.33 mg/kg, IV], detomidine hydrochloride [0.007 mg/kg, IV], or romifidine hydrochloride [0.033 mg/kg, IV] alone or in combination with butorphanol [0.007 mg/kg, IV]) in random order, with a was...
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...
Morton AJ, Grosche A, Matyjaszek SA, Polyak MM, Freeman DE.The effects of prostaglandins and nonsteroidal anti-inflammatory drugs (NSAIDs) on repair of equine intestinal mucosa are important since most horses with gastrointestinal diseases are routinely treated with NSAIDs, such as flunixin meglumine (FM), and these drugs can be toxic to equine gastrointestinal mucosa. Objective: Flunixin meglumine would not affect recovery of equine colonic mucosa in vitro, 18 h after a reversible ischaemic injury. Methods: In 14 anaesthetised horses, a segment of pelvic flexure was subjected to 2 h of ischaemia and the horses were allowed to recover for 18 h. Seven ...
Lescun TB, Ward MP, Adams SB.To compare gentamicin concentrations achieved in synovial fluid and joint tissues during IV administration and continuous intra-articular (IA) infusion of the tarsocrural joint in horses. Methods: 18 horses with clinically normal tarsocrural joints. Methods: Horses were assigned to 3 groups (6 horses/group) and administered gentamicin (6.6 mg/kg, IV, q 24 h for 4 days; group 1), a continuous IA infusion of gentamicin into the tarsocrural joint (50 mg/h for 73 hours; group 2), or both treatments (group 3). Serum, synovial fluid, and joint tissue samples were collected for measurement of gentami...
Flood J, Byrne D, Bauquier J, Agne GF, Wise JC, Medina-Torres CE, Wood K, Sullivan O, Stewart AJ.Right dorsal colitis (RDC) is a nonsteroidal anti-inflammatory drug (NSAID) induced, protein losing enteropathy in horses associated with a high case fatality rate. Objective: To describe signalment, NSAID usage, clinical presentations, clinical pathology, ultrasonographic findings, treatments, outcomes, and factors associated with survival in horses diagnosed with RDC. Methods: Thirty-five horses from 7 Australian equine hospitals diagnosed with RDC. Methods: Retrospective case series. Clinical records of cases were accepted if definitively or presumptively diagnosed by an internist with RDC ...
Kikuchi M, Ishige T, Minamijima Y, Hirota KI, Nagata SI, Tozaki T, Kakoi H, Ishiguro-Oonuma T, Kizaki K.Circulating microRNAs (miRNAs) are stable in bodily fluids and are potential biomarkers of various diseases and physiological states. Although several studies have been conducted on humans to detect drug doping by miRNAs, research on drugs and miRNAs in horses is limited. In this study, circulating miRNAs in horses after hydrocortisone administration were profiled and variations in miRNAs affected by hydrocortisone administration during endogenous hydrocortisone elevation were examined. The miRNAs were extracted from thoroughbred horse plasma before and after hydrocortisone administration and ...
Webster A, Pezzanite L, Hendrickson D, Griffenhagen G.Equine practitioners frequently inject local anaesthetics (LA) intra-articularly in both diagnosis of lameness and for pain management intra- or post-operatively with synovial endoscopy. Recent reviews of the human and veterinary literature support the concept that chondrotoxicity of LA on joint tissues depends on the type of drug, dose administered, and duration of exposure. The purpose of this review is to summarise the current literature describing intra-articular local anaesthetic use, including both in vitro and in vivo studies, and to draw some comparisons to literature from other specie...
Parhizkar P, Mohammadi R, Hashemi-Asl SM, Jalilzadeh-Amin G, Sarrafzadeh-Rezaei F.The aim of this study was to compare the sedative and cardiovascular effects of the combination of acepromazine-clonidine versus acepromazine-xylazine in horses. Four healthy cross-bred horses were included in the study. They were assigned to two treatments. In treatment I (T1), the animals received xylazine hydrochloride (1.00 mg kg) in combination with acepromazine maleate (0.05 mg kg) intravenously (IV). In treatment II (T2), the animals received intra-gastric administration of clonidine (0.002 mg kg) followed by acepromazine (0.05 mg kg; IV) after 60 min. Head height above the ground (HHAG...
