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.
Anielski P.Doping control of anabolic substances is normally carried out with urine samples taken from athletes and horses. Investigation of alternative specimens, e.g. hair samples, is restricted to special cases, but can also be worthwhile, in addition to urine analysis. Moreover, hair material is preferred in cases of limited availability or complicated collection of urine samples, e.g. from horses. In this work, possible ways of interpretation of analytical results in hair samples are discussed and illustrated by practical experiences. The results demonstrate the applicability of hair analysis to det...
Yamada M, Aramaki S, Kurosawa M, Saito K, Nakazawa H.Methandienone, methandriol, and oxymetholone, which are anabolic steroids possessing 17alpha-methyl and 17beta-hydroxy groups, were developed as oral formulations for therapeutic purposes. However, they have been used in racehorses to enhance racing performance. In humans, it has been reported that structurally related anabolic steroids having the 17alpha-methyl and 17beta-hydroxy groups, including 17alpha-methyltestosterone, mestanolone, methandienone, methandriol, and oxymetholone, have metabolites in common. In this study, we found that metabolites common to those of 17alpha-methyltestoster...
Germann SE, Matheis FL, Rampazzo A, Burger D, Roos M, Spiess BM.Only few drugs with limited efficacy are available for topical treatment of equine glaucoma. Objective: To evaluate the effect of topical administration of 1% brinzolamide on intraocular pressure (IOP) in clinically normal horses. Methods: Healthy mature horses (n = 20) with normal ocular findings, were studied. The IOP was measured 5 times daily (07.00, 11.00, 15.00, 19.00 and 23.00 h) over 10 days. On Days 1 and 2, baseline values were established. On Days 3-5 one eye of each horse was treated with one drop of 1% brinzolamide every 24 h immediately following the 07.00 h measurement. On Days ...
Lyons ET, Tolliver SC, Ionita M, Collins SS.Horse foals on five farms in Central Kentucky were used in field studies in 2007 evaluating activity of paste formulations of four compounds (fenbendazole-FBZ, ivermectin-IVM, oxibendazole-OBZ, and pyrantel pamoate-PRT) against internal parasites with emphasis on ascarids (Parascaris equorum). It has been well established the last few years that there is widespread resistance of P. equorum to ivermectin. The main purpose of the present research was to obtain current data on ascaridicidal activity of FBZ, OBZ, and PRT; also, to acquire further information on ascarid resistance to ivermectin. Ad...
Raidal SL, Edwards S.To determine the pharmacokinetics of potassium bromide (KBr) in horses after a single and multiple oral doses. Methods: Twelve adult Standardbred and Thoroughbred mares. Methods: Horses were randomly assigned into two treatment groups. In Part 1 of the study, horses were given a single oral dose of 120 mg/kg KBr. Part 2 of the study evaluated a loading dose of 120 mg/kg KBr daily by stomach tube for 5 days, followed by 40 mg/kg daily in feed for 7 days. Serum concentrations of bromide were determined by colorimetric spectrophotometry following drug administration to permit determination of con...
Sanchez LC, Elfenbein JR, Robertson SA.To evaluate effects of butorphanol, acepromazine, and N-butylscopolammonium bromide (NBB) on visceral and somatic nociception and duodenal motility in conscious, healthy horses. Methods: 6 adult horses. Methods: Visceral nociception was evaluated by use of colorectal distention (CRD) and duodenal distention (DD) threshold. Somatic nociception was evaluated via thermal threshold (TT). Nose-to-ground height, heart rate, and respiratory rate were also measured. Each horse received each treatment in randomized order; investigators were not aware of treatments. Butorphanol was administered IV as a ...
Soma LR, Rudy JA, Uboh CE, Xu F, Snapp HM.To investigate the pharmacokinetics and behavioral effects of aminorex administered IV and PO in horses. Methods: 7 Thoroughbreds. Methods: In a cross-over design, aminorex (0.03 mg/kg) was administered IV or PO. Plasma and urinary aminorex concentrations were determined via liquid chromatography- mass spectrometry. Results: Decrease of aminorex from plasma following IV administration was described by a 3-compartment pharmacokinetic model. Median (range) values of alpha, beta, and gamma half-lives were 0.04 (0.01 to 0.28), 2.30 (1.23 to 3.09), and 18.82 (8.13 to 46.64) hours, respectively. Tot...
Ho EN, Wan TS, Wong AS, Lam KK, Stewart BD.Insulin administration can increase muscle glycogen by utilising hyperinsulinaemic clamps prior to sports events or during the recovery phases, and increase muscle size by its chalonic action to inhibit protein breakdown. In order to control insulin abuse in equine sports, a method to detect effectively the use of insulins in horses would be required. Besides the readily available human insulin and its synthetic analogues, structurally similar insulins from other species can also be used as doping agents. This study describes a method for the simultaneous detection of bovine, porcine and human...
Vonaparti A, Lyris E, Panderi I, Koupparis M, Georgakopoulos C.Two simple and rapid LC/MS methods with direct injection analysis were developed and validated for the quantification and identification of hydrocortisone in equine urine using the same sample preparation but different mass spectrometric systems: ion trap mass spectrometry (IT-MS) and time-of-flight mass spectrometry (TOF-MS). The main advantage of the proposed methodology is the minimal sample preparation procedure, as particle-free diluted urine samples were directly injected into both LC/MS systems. Desonide was used as internal standard (IS). The linear range was 0.25-2.5 microg ml(-1) for...
Iff I, Mosing M, Moens Y.The objectives of this study were to measure the pressure in the caudal extradural space of standing horses and to evaluate the usefulness of pressure waves to identify correct needle placement. Caudal extradural pressure was measured in 12 healthy horses. The pressure and any extradural pressure waves were recorded for 3min after puncture, for 1min after testing for lack of resistance (LOR), and for 10min after lidocaine injection. Successful extradural drug administration was confirmed in all horses. The median extradural pressure findings after puncture, after LOR, immediately after injecti...
Lyons ET, Tolliver SC, Ionita M, Lewellen A, Collins SS.Field studies (n=6) were completed on evaluation of activity of ivermectin (200 microg/kg) paste formulation against small strongyles in horses (foals, yearlings, and older animals) on a farm (Farm MC) in Central Kentucky in late 2006 and during 2007. A girth tape was used to estimate body weights which were then used to calculate the proper dose rate of ivermectin. The foals, yearlings, and some of the older horses were born and raised on the farm. However, most of the older horses which were not raised on the farm had been there for several years. The horse herd was given ivermectin exclusiv...
Chaffin MK, Cohen ND, Martens RJ.To determine the effect of azithromycin chemoprophylaxis on the cumulative incidence of pneumonia caused by Rhodococcus equi, age at onset of pneumonia, and minimum inhibitory concentration (MIC) of azithromycin for R equi isolates cultured from fecal and clinical samples. Methods: Controlled, randomized clinical trial. Methods: 338 foals born and raised at 10 equine breeding farms; each farm had a history of endemic R equi infections. Methods: Group 1 foals were control foals, and group 2 foals were treated with azithromycin (10 mg/kg [4.5 mg/lb], PO, q 48 h) during the first 2 weeks after bi...
Colas C, Garcia P, Popot MA, Bonnaire Y, Bouchonnet S.Solid-phase extraction cartridges among those usually used for screening in horse doping analyses are tested to optimize the extraction of harpagoside (HS), harpagide (HG), and 8-para-coumaroyl harpagide (8PCHG) from plasma and urine. Extracts are analyzed by liquid chromatography coupled with multi-step tandem mass spectrometry. The extraction process retained for plasma applies BondElut PPL cartridges and provides extraction recoveries between 91% and 93%, with RSD values between 8 and 13% at 0.5 ng/mL. Two different procedures are needed to extract analytes from urine. HS and 8PCHG are extr...
Assis RA, Kuchler IL, Miekeley N, Tozzi MB.Capillary electrophoresis coupled to inductively coupled plasma mass spectrometry was used in a speciation study on disodium monomethylarsonate (DS-MMA(V)) and its metabolites in horses, to which the drug was administered by intramuscular injection on five consecutive days at a single arsenic dosage of 270 mg day(-1). Samples of urine, whole blood, plasma, and mane hair were analyzed before, during, and after drug administration. The data show that blood clearing and urinary excretion of MMA is a fast process following first-order kinetics with biological half-lives of about 38 h and 44 h for ...
Errico JA, Trumble TN, Bueno AC, Davis JL, Brown MP.To compare isolated limb retrograde venous injection (ILRVI) and isolated limb infusion (ILI) for delivery of amikacin to the synovial fluid of the distal interphalangeal and metacarpophalangeal joints and to evaluate the efficacy of use of an Esmarch tourniquet in standing horses. Methods: 6 healthy adult horses. Methods: Horses were randomly assigned in a crossover design. In ILRVI, the injection consisted of 1 g of amikacin diluted to a total volume of 60 mL administered during a 3-minute period. In ILI, the infusion consisted of 1 g of amikacin diluted to 40 mL administered during a 3-minu...
Delguste C, Amory H, Guyonnet J, Thibaud D, Garnero P, Detilleux J, Lepage OM, Doucet M.Bioavailability and pharmacological effects of tiludronate were compared when administered as an intravenous (i.v.) bolus at a dosage of 0.1 mg/kg body weight (b.w.) once daily for 10 consecutive days (group 1, n = 6) and as a single constant rate infusion (CRI) at a total dose of 1 mg/kg b.w. (group 2, n = 6) in healthy adult horses. Tiludronate and carboxy-terminal cross-linking telopeptide of type I collagen (CTX-1) were measured in plasma and urine. There was no statistically significant difference in area under the curve (AUC) and clearance (Cl) between the two groups. Bioavailability of ...
Eberspächer E, Stanley SD, Rezende M, Steffey EP.To characterize the pharmacokinetics of fentanyl and the tolerance of foals to the drug following a single application of a commercially available transdermal system (TS). Methods: Prospective experimental study. Methods: Six (two male, four female) foals aged 4-8 days, weighing 56-74 kg. Methods: After placement of a jugular sampling catheter, one fentanyl TS (FTS) containing 10.2 mg fentanyl, released at 100 microg hour(-1), was applied for 72 hours. Blood samples were withdrawn over the course of 90 hours for fentanyl plasma analysis. Before and after the study, weight, complete blood count...
Dória RG, Valadão CA, Duque JC, Farias A, Almeida RM, Netto AC.To evaluate the cardiorespiratory and behavioural effects of epidural xylazine (XYL) or clonidine (CLO) in horses. Methods: Blinded, randomized experimental study. Methods: Twelve healthy Arabian yearling horses weighing 117-204 kg were randomly allocated into two groups: XYL (n = 6) and CLO (n = 6). Methods: An epidural catheter was inserted and a facial arterial catheter was placed and the next day the horses were restrained in stocks. Baseline values for heart (HR) and respiratory (RR) rates, arterial pressure and behavioural responses were evaluated before (T0) and 10, 20, 30, 45, 60, 90 a...
Dickey EJ, McKenzie HC, Brown KA, de Solis CN.Continuous-rate infusions (CRI) of lidocaine are often used for prolonged duration but, to date, only limited time/concentration relationships administered as a short term (24 h) CRI have been reported. Objective: To determine the time/concentration profile of lidocaine and its active metabolites glycinexylidide (GX) and monoethylglycinexylidide (MEGX) during a 96 h lidocaine infusion. Methods: Lidocaine was administered to 8 mature healthy horses as a continuous rate infusion (0.05 mg/kg bwt/min) for 96 h. Blood concentrations of lidocaine, GX and MEGX were determined using high performance l...
Foreman JH, Barange A, Lawrence LM, Hungerford LL.The objective was to test the hypothesis that phenylbutazone (PBZ) alleviates lameness in an adjustable heart bar shoe model of equine foot pain. Eight Quarter Horse mares underwent 4-weekly treatments randomly: 0.9% saline placebo (SAL: 1 mL/45 kg body weight i.v.) with no lameness; SAL with lameness; PBZ (4.4 mg/kg body weight i.v.) with no lameness; and PBZ with lameness. Blinded heart rate (HR) and lameness score (LS) were assessed every 20 min for 2 h and then hourly through 9 h. At 1 h SAL or PBZ was administered. Jugular venous samples were obtained at hours 0, 1, 2, 4, 6, and 8 and wer...
Clark C, Dowling PM, Ross S, Woodbury M, Boison JO.The macrolide antibiotic tilmicosin has potential for treating bacterial respiratory tract infections in horses. A pharmacokinetic study evaluated the disposition of tilmicosin in the horse after oral (4 mg/kg) or subcutaneous (s.c.) (10 mg/kg) administration. Tilmicosin was not detected in equine plasma or tissues after oral administration at this dose. With s.c. injection, tilmicosin concentrations reached a maximum concentration of approximately 200 ng/mL in the plasma of the horses. Tilmicosin concentrations in plasma persisted with a mean residence time (MRT) of 19 h. Maximum tissue resid...
Shilo Y, Britzi M, Eytan B, Lifschitz T, Soback S, Steinman A.Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat moderate to moderately severe pain in humans. The present study investigated tramadol administration in horses by intravenous, intramuscular, oral as immediate-release and oral as sustained-release dosage-form routes. Seven horses were used in a four-way crossover study design in which racemic tramadol was administered at 2 mg/kg by each route of administration. Altogether, 23 blood samples were collected between 0 and 2880 min. The concentration of tramadol and its M1 metabolite were ...
Scotty NC, Brooks DE, Schuman Rose CD.To evaluate the in vitro efficacy of an ophthalmic drug combination against common corneal pathogens of horses. Methods: Representative isolates of 3 bacterial and 2 fungal corneal pathogens of horses. Methods: Pathogens were subjected to minimum inhibitory concentration (MIC) testing of a drug combination that consisted of equal volumes of natamycin 3.33%, tobramycin 0.3%, cefazolin 5.5%, and equine serum. Proteinase inhibitory activity of the drug combination was assessed by use of a fluorescence microplate assay with gelatin and collagen I as substrates. The MICs of the drug combination wer...
Doucet MY, Bertone AL, Hendrickson D, Hughes F, Macallister C, McClure S, Reinemeyer C, Rossier Y, Sifferman R, Vrins AA, White G, Kunkle B, Alva R....To compare efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis. Methods: Randomized controlled clinical trial. Methods: 253 client-owned horses with naturally occurring osteoarthritis. Methods: Horses were treated with firocoxib (0.1 mg/kg [0.045 mg/lb], PO, q 24 h) or phenylbutazone (4.4 mg/kg [2 mg/lb], PO, q 24 h) for 14 days. Physical examinations and lameness evaluations were performed prior to treatment and after 7 and 14 days. Clinical improvement was defined as a reduction of at least 1 lameness grade or a combined...
Haerdi-Landerer MC, Suter MM, Steiner A, Wittenbrink MM, Pickl A, Gander BA.For the treatment of septic arthritis in large animals, the local application of antibiotics as a slow release system may be an appropriate means to reach high local bioactivity and low systemic side effects and drug residues. In this study, doxycycline microspheres were developed and tested in vitro for their drug-release properties, suitability for intra-articular application and antimicrobial activity. Methods: The development of a slow release system was achieved by microencapsulation of the drug into poly(lactide-co-glycolide) microspheres by a novel ultrasonic atomization method. Drug el...
Lehner AF, Stewart J, Dafalla A, Ely KJ, Connerly AL, Jones CN, ElkHoly H, Thompson K, Tobin T, Dirikolu L.Gabapentin [1-(aminomethyl)cyclohexaneacetic acid, Neurontin], is a new anticonvulsant used as adjunctive therapy in the treatment of partial seizures in humans not controlled with standard antiseizure drugs, and it has also been used in veterinary medicine. In performance horses, gabapentin is listed as a class 3 performance-enhancing substance by the Association of Racing Commissioners International, and thus is considered to have the potential to influence the outcome of races. Therefore, we developed and validated a sensitive gas chromatographic-mass spectrometric (GC-MS) method for gabape...
Bailly-Chouriberry L, Chu-Van E, Pinel G, Garcia P, Popot MA, André-Fontaine G, Bonnaire Y, Le Bizec B.Since the Australian commercialisation of the recombinant equine growth hormone (reGH) in 1998 (EquiGen-5), Bresagen), this reGH, which differs only from eGH by an additional methionine at the N-terminal end (met-eGH), is worldwide suspected to be administered to racehorses as a doping agent. Indeed, the use of this biological drug is considered as a threat to horseracing since it acts both on growth, development or reproductive functions, and on the improvement of performances. In this work, we describe two reliable techniques based on surface plasmon resonance biosensor immunoassay (SPR-BIA)...
Sundra T, Kelty E, Rendle D.An extended-release injectable omeprazole formulation (ERIO) has become a popular treatment for equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD) where it is available; however, published data are limited and optimal treatment regimens have not been determined. Objective: To compare effects of treatment on ESGD and EGGD when an ERIO formulation is administered at either 5- or 7-day intervals. Methods: Retrospective clinical study. Methods: Case records and gastroscopy images of horses with ESGD or EGGD treated with ERIO were reviewed. Images were anonymised and...
Bailey DN.The relative binding of acetaminophen, lidocaine, phenobarbital, procainamide, quinidine, and theophylline to sera of seven mammalian species was studied. Pooled commercial sera from cow, goat, horse, human, pig, rabbit, and sheep were supplemented with 5 and 10 mM concentrations of each drug. For each serum, each drug, and each drug concentration, equilibrium dialysis was performed in duplicate against phosphate buffer (pH 7.4, 0.1 M, 4 degrees C). Percent drug bound to serum was calculated. Phenobarbital demonstrated more than 20% binding to goat, horse, human, and sheep serum at both 5 and ...
Burton AJ, Giguère S, Warner L, Alhamhoom Y, Arnold RD.Therapeutic drug monitoring in a small number of foals of various ages indicates that the standard adult dose of 6.6 mg/kg bwt q. 24 h for gentamicin is too low and a dose of 12 mg/kg bwt has been proposed. The pharmacokinetics of this dosage in foals and the ages at which this higher dose should be used have not previously been investigated. Objective: To determine the effect of age on the pharmacokinetics of a single 12 mg/kg bwt i.v. dose of gentamicin in foals. Methods: Six healthy foals were given a single i.v. dose of gentamicin at 1-3 days, 2, 4, 8 and 12 weeks of age. Plasma concentrat...
Ramirez S, Wolfsheimer KJ, Moore RM, Mora F, Bueno AC, Mirza T.The objectives of this study were to determine if phenylbutazone decreased serum thyroxine (TT4) and free thyroxine (FT4) concentrations using radioimmunoassay and equilibrium dialysis techniques in horses, and, if so, an additional objective was to determine the duration of this decreased concentration once phenylbutazone administration was discontinued. Serum TT4 and FT4 concentrations were determined before and after administration of 4.4 mg/kg of phenylbutazone i.v. bid for 5 days. Treatment with phenylbutazone caused a significant decrease in TT4 and FT4 concentrations (P < .05). Serum...
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...
Eysker M, Boersema JH, Kooyman FN.The effect of three albendazole treatments at 5-week intervals, beginning at turnout in April, on cyathostome infections in Shetland ponies was compared with the effect of sequential treatments with albendazole, oxfendazole and oxibendazole. The results showed a substantial reduction in faecal egg output after the first albendazole treatment. Since faecal egg counts remained very low, no estimation of the effect of the second treatment was possible. The third treatment with albendazole and oxibendazole was followed by an increase in faecal egg counts to values of greater than 100 eggs g-1 with...
Lucas Castillo JA, Gozalo-Marcilla M, Werneck Fonseca M, Possebon FS, da Rosa AC, de Araujo Aguiar AJ.Information on appropriate protocols for sedation of Nordestino donkeys is scarce. Objective: To evaluate the sedative and cardiorespiratory effects of low doses of intravenous (i.v.) xylazine with and without acepromazine in 'Nordestino' donkeys. Methods: Seven healthy female Nordestino donkeys (150 ± 18 kg) were included in this blinded, randomised, crossover experiment. Methods: Four treatments were administered, consisting of two i.v. injections, at baseline (T0, 1st injection) and 15 min later (T15, 2nd injection). Treatments included acepromazine 0.05 mg/kg bwt + saline (AS), saline + x...
Kondampati KD, Saini SPS, Sidhu PK, Anand A, Kumar D, Beesam S, Bedi JS, Kaur R, Bhardwaj R.The pharmacokinetics of ampicillin-cloxacillin, given as single intravenously dose of 10 mg.kg-1 (5 mg.kg-1 of ampicillin plus 5 mg.kg-1 of cloxacillin) was examined in clinically presented Indian thoroughbred horses (n = 6) in order to design appropriate dosing strategies. Drug concentrations in plasma were determined by high performance liquid chromatography (HPLC) and pharmacokinetic parameters were derived by non-compartmental analysis using WinNonlin software. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of ampicillin-cloxacillin against qualit...
Mason ME, Voris ND, Ortis HA, Geeding AA, Kaplan RM.To compare larvicidal regimens of fenbendazole and moxidectin for reduction and suppression of cyathostomin fecal egg counts (FEC) in a transient herd of embryo transfer-recipient mares. Methods: Randomized, complete block, clinical trial. Methods: 120 mares from 21 states, residing on 1 farm. Methods: An initial fecal sample was collected from each mare; mares with an FEC ≥ 200 eggs/g were assigned to treatment groups. Eighty-two horses received fenbendazole (10.0 mg/kg [4.5 mg/lb], PO, q 24 h for 5 days) or moxidectin (0.4 mg/kg [0.18 mg/lb], PO, once); FEC data were analyzed 14, 45, and 9...
Törneke MK, Ingvast-Larsson JC, Johansson JM, Appelgren LE.To determine pharmacokinetics of terbutaline in healthy horses and to relate serum terbutaline concentrations with the drug's pharmacodynamic effects. Methods: 6 healthy horses. Methods: Horses were given terbutaline i.v. (10 microg/kg of body weight) and, 1 week later, p.o. (100 microg/kg). Responses to drug administration (eg, heart rate and serum lactate concentration) were measured. Serum terbutaline concentration was measured by means of gas chromatography with mass spectrometry. Protein binding was determined in vitro. Results: Following i.v. administration, median maximum serum terbutal...
Troya-Portillo L, López-Sanromán J, Villalba-Orero M, Santiago-Llorente I.Standing surgery under sedation reduces anesthetic-related mortality in horses. Medetomidine, alone and combined with morphine in a constant rate infusion (CRI), has been described for standing surgery but their cardiorespiratory, sedative and antinociceptive effects have never been compared. The addition of ketamine could improve analgesia in these procedures with minimal cardiorespiratory consequences. The objectives were to compare the cardiorespiratory effects, quality of sedation, antinociception and ataxia produced by administration of a medetomidine-based CRI with morphine, ketamine or ...
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...
You Y, Proctor RM, Guo K, Li X, Xue E, Guan F, Robinson MA.High-resolution mass spectrometry (HRMS) is a very powerful technology for equine doping control analysis. The more recently developed hybrid type of Orbitrap-based HRMS instrument allows for both targeted and non-targeted screening analyses in a single liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS) run. In the present study, an LC-HRMS/MS method was developed and validated to detect prohibited substances in equine sports. The substances were recovered from equine plasma by liquid-liquid extraction (LLE) using methyl tert-butyl ether and were separated on a C18 rev...
Jaussaud P, Courtot D, Guyot JL, Paris J.The main metabolite of flunixin, a hydroxylated product, has been identified by gas chromatography-mass spectrometry and 1H NMR spectroscopy in equine urine and plasma. The method also permits the qualitative monitoring of the urinary elimination of the drug and its metabolite. The two products are detected up to 175 and 54 h, respectively, after a single intravenous administration at the dose of 1 mg/kg. Simultaneous detection of the two compounds increases the reliability of anti-doping control analysis.
Green SL, Conlon PD.The pharmacokinetics of amikacin, administered iv at 7 mg/kg, every 8 h, were evaluated over the first 48 h of hospitalisation in 7 critically ill hypoxic premature foals and compared with those in 8 full-term nonhypoxic critically ill neonatal foals. The pharmacokinetic data were used to calculate dosage schedules that would maintain the plasma amikacin concentrations in individual foals within a target range of > or = 15 micrograms/ml but < 30 micrograms/ml for peak values and < or = 3 micrograms/ml for trough values. The results indicated a statistically significant increase in the amikacin...
Harkins JD, Queiroz-Neto A, Mundy GD, West D, Tobin T.This report describes the development of a behaviour chamber and the validation of the chamber of measure locomotor activity of a horse. Locomotor activity was detected by four Mini-beam sensors and recorded on a data logger every 5 min for 22 h. Horses were more active during daytime than in the evening, which was at least partially related to human activity in their surroundings. To validate the ability of the chambers to detect changes in activity, fentanyl citrate and xylazine HCl, agents well-characterized as a stimulant and a depressant, respectively, were administered to five horses. Fe...
Shelver WL, Thorson JF, Hammer CJ, Smith DJ.Three horses were dosed with dietary zilpaterol and the urine concentrations measured from withdrawal day 0 to withdrawal day 21. The analyses were carried out using both enzyme-linked immunosorbent assay (ELISA) and an ultraperformance liquid chromatography with triple-quadrupole-tandem mass spectrometric detection (UPLC-MS/MS). The UPLC-MS/MS method was developed to provide rapid analysis with positive analyte identification by following three product ions and computing the two independent ion ratios. When urinary zilpaterol concentrations were between 0.2 and 2 ng/mL, the ELISA had interday...
Leiberich M, Marais HJ, Naidoo V.The plight of the white rhinoceros () and the increasing need of treatment options for injured poaching victims led to the necessity to expand the knowledge on applicable drugs in this endangered species. With very little information available on drug pharmacokinetics in rhino, veterinarians have to rely on information generated from other species. The horse being a closely related species, has served as the model for dose extrapolations. However, from recent research on enrofloxacin and carprofen, the white rhino showed considerable differences in the pharmacokinetic properties of these drugs...
Yuen KY, Gibson JS, Hinrichsen S, Medina-Torres CE, Bertin FR, Stewart AJ.Prudent use of antimicrobials is paramount to slow the development of resistance and for successful treatment. The use of cumulative antibiograms will allow evidence-based antimicrobial selection with consideration of local resistance patterns. We generated a "first-isolate-per-patient" cumulative antibiogram for a regional equine referral hospital. Bacterial organisms cultured from horses between 2011 and 2018, sample origin, antimicrobial susceptibilities, and multidrug-resistant (MDR) status were tabulated. Of 1,176 samples, 50% were culture positive. Overall, 93 of 374 (25%) were MDR. Of t...
Daunt DA, Dunlop CI, Chapman PL, Shafer SL, Ruskoaho H, Vakkuri O, Hodgson DS, Tyler LM, Maze M.Cardiopulmonary and behavioral responses to detomidine, a potent alpha 2-adrenergic agonist, were determined at 4 plasma concentrations in standing horses. After instrumentation and baseline measurements in 7 horses (mean +/- SD for age and body weight, 6 +/- 2 years, and 531 +/- 48.5 kg, respectively), detomidine was infused to maintain 4 plasma concentrations: 2.1 +/- 0.5 (infusion 1), 7.2 +/- 3.5 (infusion 2), 19.1 +/- 5.1. (infusion 3), and 42.9 +/- 10 (infusion 4) ng/ml, by use of a computer-controlled infusion system. Detomidine caused concentration-dependent sedation and somnolence. The...
Cox S, Villarino N, Doherty T.The determination of the pharmacokinetic parameters of tramadol in plasma and a better characterization of its metabolites after oral administration to horses is necessary to design dosage regimens to achieve target plasma concentrations that are associated with analgesia. The purpose of this study was to determine the pharmacokinetics and elimination pattern in urine of tramadol and its metabolites after oral administration to horses. Tramadol was administered orally to six horses and its half-life, T(max) and C(max) in plasma were 10.1, 0.59 h, and 132.7 ng/mL, respectively. The half-life, T...
Webster JH, Baird JD, Gunawan M, Martin IC, Kelly JD.The susceptibility of a known thiabendazole-resistant population of small strongyles to anthelmintics of both benzimidazole and non-benzimidazole groups, was determined. In the first study, 42 horses infected with thiabendazole-resistant small strongyles were allocated to 6 groups. Treatment groups received one of the following anthelmintics: mebendazole, febantel, febantel plus trichlorphon, morantel tartrate, or a combination of thiabendazole, piperazine and trichlorphon. Morantel tartrate and the thiabendazole/piperazine/trichlorphon combination produced highly significant (p less than 0.00...
Prades M, Brown MP, Gronwall R, Houston AE.After single oral administration of ketoconazole (30 mg/kg bodyweight [bwt]) in 50 ml of corn syrup to a healthy mare, the drug was not detected in serum. Ketoconazole in 0.2 N HC1 was administered intragastrically to six healthy adult horses in five consecutive doses of 30 mg/kg bwt at 12 h intervals. Ketoconazole concentrations were measured in serum, synovial fluid, peritoneal fluid, cerebrospinal fluid (CSF), urine and endometrium. Mean peak serum ketoconazole concentration was 3.76 micrograms/ml at 1.5 to 2 h after intragastric administration. Mean peak synovial concentration was 0.87 mic...
Greene SA, Thurmon JC, Tranquilli WJ, Benson GJ.Serum insulin and plasma glucose concentrations were determined in 8 mares. Four IV treatments were studied: xylazine (1.1 mg/kg of body weight); yohimbine (0.125 mg/kg); yohimbine (0.125 mg/kg) followed 5 minutes later by xylazine (1.1 mg/kg); and 5 ml of isotonic saline solution as a control. Blood samples were collected before (time 0) and at 5, 15, 30, 60, 120, and 180 minutes after drug administration. Serum insulin concentration decreased and plasma glucose concentration increased in mares given xylazine. Plasma glucose concentration was unchanged in control mares and in mares given yohi...
Dumasia MC, Houghton E.A method for the screening and confirmatory analysis of beta-agonists and -antagonists in equine urine is described. Following initial enzymic hydrolysis, the basic drugs and metabolites are extracted using Clean Screen DAU or Bond Elut Certify cartridges, and analysed as their trimethylsilyl ether or 2-(dimethyl) silamorpholine derivatives by capillary gas chromatography-mass spectrometry. The method proved to be very sensitive and selective for basic drugs. After administration of therapeutic doses of propranolol, metoprolol, timolol, isoxsuprine and clenbuterol to thoroughbred horses, the p...
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...
Bauquier JR, Tennent-Brown BS, Tudor E, Bailey SR.Doramapimod (BIRB-796-BS), is an anti-inflammatory compound, acting through p38 MAPK inhibition, but its anti-inflammatory effects have not previously been studied in the horse. Whole blood aliquots from healthy horses diluted 1:1 with cell culture medium were incubated for 21 h with 1 μg/ml of lipopolysaccharide (LPS), lipoteichoic acid (LTA) or peptidoglycan (PGN) in the presence of increasing concentrations of doramapimod (3 × 10 M to 10 M). Cell bioassays were used to measure TNF-α and IL-1β activity. Doramapimod significantly and potently inhibited TNF-α and IL-1β activity induced b...
Knych HK, Corado CR, McKemie DS, Scholtz E, Sams R.Tramadol is a synthetic opioid used in human medicine, and to a lesser extent in veterinary medicine, for the treatment of both acute and chronic pain. In humans, the analgesic effects are owing to the actions of both the parent compound and an active metabolite (M1). The goal of the current study was to extend current knowledge of the pharmacokinetics of tramadol and M1 following oral administration of three doses of tramadol to horses. A total of nine healthy adult horses received a single oral administration of 3, 6, and 9 mg/kg of tramadol via nasogastric tube. Blood samples were collected...
Eberspächer E, Stanley SD, Rezende M, Steffey EP.To characterize the pharmacokinetics of fentanyl and the tolerance of foals to the drug following a single application of a commercially available transdermal system (TS). Methods: Prospective experimental study. Methods: Six (two male, four female) foals aged 4-8 days, weighing 56-74 kg. Methods: After placement of a jugular sampling catheter, one fentanyl TS (FTS) containing 10.2 mg fentanyl, released at 100 microg hour(-1), was applied for 72 hours. Blood samples were withdrawn over the course of 90 hours for fentanyl plasma analysis. Before and after the study, weight, complete blood count...
Gronert GA, Fung DL, Jones JH, Shafer SL, Hildebrand SV, Disbrow EA.We investigated the effects of body size on the pharmacokinetics and pharmacodynamics of the renally cleared muscle relaxant metocurine. We hypothesized that pharmacokinetics of the drug would change allometrically in proportion to physiological time [infinity Mb0.25, where Mb is body mass] and that pharmacodynamics would be independent of size because of the highly conserved structure of the acetylcholine receptor. Metocurine effects during general anesthesia were examined in 17 rats, 8 cats, 6 dogs, 5 pigs, 7 sheep, and 12 horses. Allometric analysis demonstrated size dependence for pharmaco...
