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.
Ringer SK, Portier K, Torgerson PR, Castagno R, Bettschart-Wolfensberger R.To compare xylazine and romifidine constant rate infusion (CRI) protocols regarding degree of sedation, and effects on postural instability (PI), ataxia during motion (A) and reaction to different stimuli. Methods: Blinded randomized experimental cross-over study. Methods: Ten adult horses. Methods: Degree of sedation was assessed by head height above ground (HHAG). Effects on PI, A and reaction to visual, tactile and acoustic stimulation were assessed by numerical rating scale (NRS) and by visual analogue scale (VAS). After baseline measurements, horses were sedated by intravenous loading dos...
Casella S, Giannetto C, Giudice E, Marafioti S, Fazio F, Assenza A, Piccione G.Adenosine diphosphate (ADP)-induced platelet aggregation in fed and fasted horses after addition of tramadol hydrochloride was evaluated in vitro. On 10 horses citrated blood samples were collected 2h after feeding (fed animals) and 21 h after feeding (fasted animals). Final concentrations of ADP 1 and 0.5 μM, and tramadol hydrochloride (1, 15, 30, 45 and 60 min after the addition of tramadol) were used to determine the maximum degree and initial velocity of platelet aggregation. Repeated measures multifactor analysis of variance (MANOVA) was used to evaluate the effect of feeding/fasting con...
Duesterdieck-Zellmer KF, Driscoll N, Ott JF.To determine concentration-dependent effects of tiludronate on cartilage explants incubated with or without recombinant equine interleukin-1β (rEq IL-1). Methods: Articular cartilage explants from the femorotibial joints of 3 young adult horses. Methods: Cartilage explants were incubated with 1 of 6 concentrations (0, 0.19, 1.9, 19, 190, or 1,900 mg/L) of tiludronate and with or without rEq IL-1 (0.01 ng/mL) for 96 hours. Prostaglandin E(2) (PGE(2)) concentrations in culture medium and explant digests were analyzed via PGE(2) enzyme immunoassay. Sulfated glycosaminoglycan (sGAG) concentration...
Ho EN, Kwok WH, Lau MY, Wong AS, Wan TS, Lam KK, Schiff PJ, Stewart BD.A veterinary preparation known as TB-500 and containing a synthetic version of the naturally occurring peptide LKKTETQ has emerged. The peptide segment (17)LKKTETQ(23) is the active site within the protein thymosin β(4) responsible for actin binding, cell migration and wound healing. The key ingredient of TB-500 is the peptide LKKTETQ with artificial acetylation of the N-terminus. TB-500 is claimed to promote endothelial cell differentiation, angiogenesis in dermal tissues, keratinocyte migration, collagen deposition and decrease inflammation. In order to control the misuse of TB-500 in equin...
Hughes LA, Pinchbeck G, Callaby R, Dawson S, Clegg P, Williams N.Antimicrobial use is known to select for the emergence of resistant strains of bacteria; therefore prudent use in both human and veterinary medicine is essential to preserve their efficacy. Objective: To characterise antimicrobial prescribing patterns in UK equine practice and evaluate factors associated with prescribing. Methods: A postal questionnaire including 4 clinical scenarios was sent to 740 veterinary surgeons that treat horses. Data were collected on the clinician, their practice and sources of information regarding antimicrobials and their use. Multivariable logistic regression anal...
Naylor RJ, Luis-Fuentes V, Livesey L, Mobley CB, Henke N, Brock K, Fernandez-Fuente M, Piercy RJ.Type 1 polysaccharide storage myopathy (PSSM1), an equine glycogen storage disorder caused by a gain of function mutation (R309H) in the gene encoding glycogen synthase (GYS1), is associated with the accumulation of amylase-resistant alpha-crystalline polysaccharide inclusions within skeletal muscle. Several glycogenoses in humans have a cardiac phenotype, and reports exist of horses with PSSM and polysaccharide inclusions in cardiac muscle. Objective: To investigate the hypothesis that horses with PSSM1 display a cardiac phenotype. Our objectives were to compare plasma cardiac troponin I (cTn...
Möller I, Thomas A, Wingender A, Machnik M, Schänzer W, Thevis M.Erythropoietin (EPO) and its recombinant analogues are suspected to be illicitly administered to horses for performance enhancing purposes and, consequently, prohibited in equine sports. Recently, a new erythropoiesis-stimulating agent, peginesatide (Omontys, formerly referred to as Hematide), belonging to the upcoming class of EPO-mimetic peptides, received approval for the treatment of anaemia in humans with chronic kidney disease on dialysis. As the pegylated dimeric peptide of approximately 45 kDa without sequence homology to EPO is not detectable by conventional EPO detection assays, spec...
Vudathala D, Murphy L.A simple and highly sensitive LC/MS method was developed for the simultaneous determination of six ionophores--lasalocid, monensin, laidlomycin, maduramycin, salinomycin, and narasin--in feed. The procedure involved extraction of 1 g of feed with 4 mL of methanol-water (9 + 1, v/v) by shaking on a platform shaker for 45 min. After centrifugation, the extracts were diluted with methanol-water (75 + 25, v/v) and analyzed without any cleanup. The analysis was performed on a Betasil C18 column (150 x 4.6 mm id, 5 pm particle size) connected to an LC/MS system operated in the atmospheric pressure c...
Lyons ET, Tolliver SC.Critical tests were performed in 2011 in four weanling horses (L-1, L-2, L-29, and L-30) treated with ivermectin paste at 200 μg/kg. They were born in 2011 and raised together on a farm (MC) in Central Kentucky. The horses had not been treated previously with an antiparasitic drug. However, ivermectin had been administered repeatedly to the horse herd for several years and strongyle eggs per gram of feces (EPGs) returned sooner posttreatment than after initial usage. Critical tests in a recent previous study in this horse herd indicated that the reason for the early return of strongyle EPGs a...
Ho EN, Kwok WH, Wong AS, Wan TS.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 due to significant improvement in high resolution mass spectrometry in terms of sensitivity, mass accuracy, mass resolution, and mass stability. A number of HRAMS methods have been reported for the detection of multi-drug residues in human or equine urine. As blood has become a common matrix for doping control analysis, especially in equine sports, a sensitive, fast and wide coverage screening method for detecting a large number of drugs in equine ...
DeRossi R, Maciel FB, Módolo TJ, Pagliosa RC.To evaluate perineal analgesic effects of 3 doses of neostigmine coadministered epidurally with lidocaine to geldings. Methods: 6 healthy geldings. Methods: A few days before each treatment, a catheter was inserted between the first and second coccygeal vertebrae via the caudal approach in each gelding; the catheter tip was threaded approximately 10 cm cranial into the midsacral region. Each horse received 4 epidural treatments: 2% lidocaine (0.2 mg/kg) alone and 3 doses of neostigmine (0.5, 1, or 2 μg/kg) coadministered with that same dose of lidocaine. Horses were restrained in stocks in a ...
Ambrisko TD, Coppens P, Kabes R, Moens Y.This study compares cardiac output (CO) measurements obtained by lithium dilution (LiDCO), pulse power analysis (PulseCO), and continuous thermodilution (CTD) with bolus thermodilution (BTD) in ponies. Methods: Eight isoflurane-anaesthetized Shetland ponies received xylazine, ketamine, and midazolam infusions (0.3, 1.2, and 0.018 mg kg(-1) h(-1), respectively). CO was measured with BTD, CTD, LiDCO, and PulseCO. Lithium was injected into the jugular vein and blood was sampled from the facial artery for lithium detection and this artery was also used for PulseCO. Measurements were obtained durin...
Czerwinski SL, Lyon AW, Skorobohach B, Léguillette R.Ophthalmic antibiotic therapy in large animals is often used empirically because of the lack of pharmacokinetics studies. The purpose of the study was to determine the pharmacokinetics of topical tobramycin 0.3% ophthalmic solution in the tears of normal horses using an automated immunoassay analysis. Results: The mean tobramycin concentrations in the tears at 5, 10, 15, 30 minutes and 1, 2, 4, 6 hours after administration were 759 (±414), 489 (±237), 346 (±227), 147 (±264), 27.6 (±28.4), 14.8 (±66.6), 6.7 (±18.6), and 23.4 (±73.4) mg/L. Mean tobramycin concentration was maintained abo...
Noble G, Edwards S, Lievaart J, Pippia J, Boston R, Raidal SL.Safety of meloxicam, a potent NSAID with selective COX-2 inhibition, has not been evaluated in horses. Objective: To evaluate pharmacokinetics and safety of single and repeated oral doses of meloxicam in adult horses. Methods: Forty-nine healthy, university-owned adult lightbreed horses. Methods: Study conducted in 2 parts. Part I addressed pharmacokinetics of single oral dose meloxicam (0.6 mg/kg) in 16 horses. Part II, 33 horses were randomly assigned to 5 treatment groups to assess prolonged administration (0.6 mg/kg PO q24h for 6 weeks, n = 7) or higher doses (1.8 mg/kg, n = 7, or 3.0 mg/k...
Gozalo-Marcilla M, Hopster K, Gasthuys F, Hatz L, Krajewski AE, Schauvliege S.Dexmedetomidine has been administered in the equine as a constant-rate infusion (CRI) during inhalation anaesthesia, preserving optimal cardiopulmonary function with calm and coordinated recoveries. Inhalant anaesthetic sparing effects have been demonstrated in other species, but not in horses. Objective: To determine the effects of a CRI of dexmedetomidine on the minimal alveolar concentration (MAC) of sevoflurane in ponies. Methods: Six healthy adult ponies were involved in this prospective, randomised, crossover, blinded, experimental study. Each pony was anaesthetised twice (3 weeks washou...
McGorum BC, Nicholas DR, Foster AP, Shaw DJ, Pirie RS.Bronchodilators are frequently used to attenuate airway obstruction in equine heaves (or recurrent airway obstruction). This study evaluated the selective (M(3) and M(1)) muscarinic antagonist revatropate, which offers potential advantages over non-specific antimuscarinic agents such as ipratropium. Protocol 1 assessed the response to inhaled revatropate (1, 2 and 7 mg) using a blinded, negative (inhaled saline) and positive (inhaled ipratropium bromide; 0.3, 0.7 and 2mg) controlled, dose escalation study, with six heaves horses. The lowest doses of revatropate and ipratropium induced a rapid ...
Ringer SK, Schwarzwald CC, Portier KG, Ritter A, Bettschart-Wolfensberger R.The objective of this study was to compare the cardiopulmonary effects of a xylazine or romifidine loading-dose, followed by a constant rate infusion (CRI) of the same α(2)-agonist. Nine research horses were treated in a randomized, blinded, crossover design with xylazine or romifidine. After instrumentation, a loading dose of intravenous xylazine (1mg/kg) or romifidine (80μg/kg) was administered, immediately followed by a CRI of xylazine (0.69mg/kg/h) or romifidine (30μg/kg/h) for a duration of 2h. Cardiopulmonary variables were recorded before bolus administration, during CRI, and for 1h ...
Kwan C, Bell R, Koenig T, Bischofberger A, Horadagoda N, Perkins NR, Jeffcott LB, Dart AJ.Evaluate synovial fluid cytology, total protein concentration and viscosity after intra-articular administration of combined pentosan polysulfate and glucosamine in horses. Methods: Ten adult Standardbred horses had each carpal joint (n = 20) randomly assigned to one of two treatments: control (5 mL saline) or treated (pentosan polysulfate and glucosamine). All horses received an intra-articular injection every 7 days for 3 weeks and synovial fluid samples were collected on days 1 (baseline), 2, 3, 7, 8, 9, 14, 15, 16 and 21. Synovial fluid variables measured included total protein concentrati...
Brophy PM, MacKintosh N, Morphew RM.Anthelmintics are the cornerstone of parasitic helminth control. Surprisingly, understanding of the biochemical pathways used by parasitic helminths to detoxify anthelmintics is fragmented, despite the increasing global threat of anthelmintic resistance within the ruminant and equine industries. Reductionist biochemistry has likely over-estimated the enzymatic role of glutathione transferases in anthelmintic metabolism and neglected the potential role of the cytochrome P-450 superfamily (CYPs). Proteomic technologies offers the opportunity to support genomics, reverse genetics and pharmacokine...
Kwok WH, Ho EN, Leung GN, Tang FP, Wan TS, Wong HN, Yeung JH.1-Testosterone (17β-hydroxy-5α-androst-1-en-3-one), a synthetic anabolic steroid, has been described as one of the most effective muscle-building supplements currently on the market. It has an anabolic potency of 200 as compared to 26 for testosterone. Apart from its abuse in human sports, it can also be a doping agent in racehorses. Metabolic studies on 1-testosterone have only been reported for human in the early seventies, whereas little is known about its metabolic fate in horses. This paper describes the studies of in vitro and in vivo metabolism of 1-testosterone in horses, with the ai...
Sundra TM, Harrison JL, Lester GD, Raidal SL, Phillips JK.The effects of hyoscine-N-butylbromide (hyoscine) and propantheline-bromide (propantheline) on heart rate (HR), HR variability (HRV) and gastrointestinal tract (GIT) contractions in the normal horse were determined. Five adult horses had ECG recordings for 180 min after treatment with propantheline (100mg), hyoscine (120 mg) or saline. Both propantheline and hyoscine reduced GIT sounds, with propantheline having a longer duration of effect (≥120 min). Both drugs elevated HR relative to the control baseline period (P<0.05), with the effects of propantheline again being of longer duration. ...
Soma LR, Uboh CE, Liu Y, Li X, Robinson MA, Boston RC, Colahan PT.This study investigated and compared the pharmacokinetics of intra-articular (IA) administration of dexamethasone sodium phosphate (DSP) into three equine joints, femoropatellar (IAS), radiocarpal (IAC), and metacarpophalangeal (IAF), and the intramuscular (IM), oral (PO) and intravenous (IV) administrations. No significant differences in the pharmacokinetic estimates between the three joints were observed with the exception of maximum concentration (Cmax ) and time to maximum concentration (Tmax ). Median (range) Cmax for the IAC, IAF, and IAS were 16.9 (14.6-35.4), 23.4 (13.5-73.0), and 46.9...
Smiet E, Haritova A, Heil BA, Fink-Gremmels J, Wijnberg ID.To compare the pharmacokinetics of the fourth generation cephalosporin, cefquinome, in neonatal foals, 6-week-old foals and mature New Forest ponies in order to recommend appropriate dosage regimens for use of this drug. Methods: Cefquinome was administered i.v. at 1 mg/kg bwt twice a day (q. 12 h), 1 mg/kg bwt 3 times a day (q. 8 h) or 4.5 mg/kg bwt q. 12 h to each age group (n = 6). Plasma cefquinome concentrations were analysed using high-performance liquid chromatography combined with electrospray tandem mass spectrometry. Results: Both foal age groups had comparable pharmacokinetic data e...
Wang CC, Hartmann-Fischbach P, Krueger TR, Wells TL, Feineman AR, Compton JC.3,4-Methylenedioxypyrovalerone (MDPV) is a psychoactive drug with potent stimulant properties and potential for abuse and drug dependency. MDPV was recently classified as a Class I drug by Racing Commissioners International, indicating that it is a banned substance in equine athletes because it lacks therapeutic value in horses. To enforce this ban, a sensitive and fast liquid chromatography-tandem mass spectrometry method was needed. It is for this reason that this method was developed for quantification and confirmation of MDPV in equine plasma. Sample preparation involved liquid-liquid extr...
Lizarraga I, Beths T.To compare the effects of xylazine on mechanical nociceptive thresholds in donkeys and horses. Methods: Randomized, controlled, crossover, Latin-square, operator-blinded design. Methods: Six 3.1 ± 0.89 year old standard donkeys weighing 145.0 ± 30.5 kg and six 9.6 ± 4.4 year old Thoroughbred horses weighing 456.0 ± 69.0 kg. Methods: Each animal received one of four doses of xylazine (0.5, 0.7, 0.9, and 1.1 mg kg(-1) ), or acepromazine (0.05 mg kg(-1) ) or saline solution (0.9%) intravenously and mechanical nociceptive thresholds were assessed over 90 minutes. The areas under the threshold ...
Rydevik A, Bondesson U, Hedeland M.Bupivacaine is a local anaesthetic prohibited in equine sports. It is highly metabolized in the horse but a thorough description of its metabolite profile is lacking. An administration study should find appropriate analytical targets for doping control. Furthermore, knowledge of an in vitro system for production of metabolites would be beneficial. Methods: Marcain® (bupivacaine hydrochloride) was administered subcutaneously to a horse and urine samples were collected. In vitro metabolic systems consisting of the fungi Cunninghamella elegans and Cunninghamella blakesleeana were incubated with ...
Steckler D, Naidoo V, Gerber D, Kähn W.To determine the intercyclic effect of oxytocin and carbetocin on equine myometrial tissue, the effect of the drugs was evaluated through pharmacokinetic and pharmacodynamic studies. The complete pharmacokinetic profile for oxytocin was unknown and had to be established. To do so, 25 IU of oxytocin were administered intravenously to six cycling mares and blood samples were collected before and 2, 4, 8, and 15 min after administration. The half-life of oxytocin was determined to be 5.89 min, the clearance rate 11.67 L/min, mean residence time (MRT) 7.78 min. The effective plasma concentration w...
Schneiders FI, Noble GK, Boston RC, Dunstan AJ, Sillence MN, McKinney AR.Acepromazine (ACP) is a useful therapeutic drug, but is a prohibited substance in competition horses. The illicit use of ACP is difficult to detect due to its rapid metabolism, so this study investigated the ACP metabolite 2-(1-hydroxyethyl)promazine sulphoxide (HEPS) as a potential forensic marker. Acepromazine maleate, equivalent to 30mg of ACP, was given IV to 12 racing-bred geldings. Blood and urine were collected for 7days post-administration and analysed for ACP and HEPS by liquid chromatography-mass spectrometry (LC-MS). Acepromazine was quantifiable in plasma for up to 3h with little r...
Gray BP, Biddle S, Pearce CM, Hillyer L.Fluticasone propionate (FP) is an anti-inflammatory agent with topical and inhaled applications commonly used in the treatment of asthma in steroid-dependent individuals. The drug is used in racehorses to treat Inflammatory Airway Disease; this work was performed in order to advise on its use and detect potential misuse close to racing. Methods were developed for the extraction and analysis of FP from horse plasma and a carboxylic acid metabolite (FP-17βCOOH) from horse urine. The methods utilize ultra high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) in ...
Johns I, Verheyen K, Good L, Rycroft A.The objective of this study was to examine the emergence and persistence of antimicrobial resistant faecal Escherichia coli in horses treated with antimicrobial drugs in a hospital and community setting. Faecal samples were collected from hospitalised (n=56) and non-hospitalised (n=14) horses treated with antimicrobials, and 10 non-treated hospitalised controls. Samples were obtained pre-treatment and 5 days later in all horses, and 2 weeks and 2 months after treatment in treated horses. Susceptibility to 15 antimicrobials was tested via disc diffusion on up to 3 E. coli isolates per sample. P...
Fenwick SJ, Scarth JP.Within horseracing, the detection of prohibited substance doping often requires urine analysis; hence, it is necessary to understand the metabolism of the drugs in question. Here, the previously unknown equine metabolism of eight sedatives is reported in order to provide information on target metabolites for use in doping control. Phase I metabolite information was provided by incubation with equine liver S9 fraction. In vitro techniques were chosen in order to reduce the ethical and financial issues surrounding the study of so many compounds, none of which are licensed for use in horses in th...
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)...
Souza C, Villarino NF, Farnsworth K, Black ME.Electroporation is a method used to deliver poorly permeant chemotherapeutic drugs to tumor cells, potentiating the cytotoxic effects of drugs and overall clinical response. Despite existing evidence of the potential benefits of electroporation to enhance the antitumoral effects of drugs, there is a lack of understanding about the effects of electroporation on equine tumor cells. This study investigated the combined effects of electroporation and bleomycin, cisplatin, and carboplatin on an equine sarcoid cell line (EqS04b). The use of electroporation increases the cytotoxic effects of bleomyci...
Mosing M, Auer U, Bardell D, Jones RS, Hunter JM.This clinical study evaluated the speed of reversal of profound rocuronium block in ponies using sugammadex and investigated the differences in onset and recovery from block in three different muscle groups. Methods: Anaesthesia was induced and maintained with isoflurane in oxygen 100% in eight ponies. Neuromuscular monitoring was performed at each site using acceleromyography: in the extensor muscles of the pelvic limb (peroneal nerve) and thoracic limb (radial nerve), and in the orbicularis oris muscle (OOM; facial nerve). Rocuronium 0.6 mg kg(-1) i.v. was administered, followed 5 min later ...
Kamerling SG, Cravens WM, Bagwell CA.The effects of detomidine, a veterinary sedative analgesic, were studied in the horse. Novel objective techniques were employed to assess the analgesic and sedative potency of this compound. Intravenous doses of 0.010, 0.020 and 0.040 mg/kg were administered to eight adult Thoroughbred racehorses according to a double-blind crossover design. Analgesia was measured by determining the latency to onset of the skin twitch and hoof withdrawal reflexes following noxious thermal stimulation of the withers and fetlock, respectively. Sedation was assessed by quantifying spontaneous locomotor activity i...
Fadel C, Giorgi M.According to in vitro and in vivo investigations, firocoxib (FX), a second-generation coxib, is a highly selective COX-2 inhibitor in horses. With a COX-1/COX-2 IC50 ratio of 643 in horses, FX spares the COX-1 inhibitory effects. It is approved for the treatment of musculoskeletal problems and lameness in horses and dogs with osteoarthritis (OA). For the treatment of OA in horses, both an injectable formulation for IV administration at a dose of 0.09 mg/kg for five days and an oral paste formulation at a dose of 0.1 mg/kg for 14 days are licensed. Numerous analytical methods were reported in...
Belloli C, Carcano R, Arioli F, Beretta C.We used isolated equine digital arteries to study the vasodilatory mechanism of isoxsuprine, and fowl caecum preparations to investigate the affinity of the drug for beta-adrenoceptors. Isoxsuprine is a potent vasodilator of arterial smooth muscle that has been precontracted by an alpha-adrenoceptor agonist such as noradrenaline (log EC50 = -6.33 [-5.98; -6.68]). The present study indicates that its effect is due to alpha-adrenoceptor blockade since: (1) after a long lasting exposure to cumulative doses of isoxsuprine the vasoconstricting action of noradrenaline cannot be restored; (2) isoxsup...
Derochette S, Serteyn D, Mouithys-Mickalad A, Ceusters J, Deby-Dupont G, Neven P, Franck T.Excessive neutrophil stimulation and reactive oxygen species (ROS) production are involved in numerous human or horse pathologies. The modulation of the neutrophil NADPH oxidase (NOX) has a great therapeutic potential since this enzyme produces superoxide anion whose most of the other ROS derive. The measurement of NOX activity by cell-free systems is often used to test potential inhibitors of the enzyme. A major drawback of this technique is the possible interferences between inhibitors and the probe, ferricytochrome c, used to measure the activity. We designed the "EquiNox2", a new pharmacol...
Ellis KE, Council-Troche RM, Von Dollen KA, Beachler TM, Bailey CS, Davis JL, Lyle SK.Hospitalized pregnant mares being held nil per os (PO) because of medical or surgical events present a dilemma for pregnancy maintenance therapy, which commonly includes oral altrenogest. Rectal administration of medications is a recognized route for achieving systemic concentrations, but there are no data on the pharmacokinetics of rectal altrenogest administration in horses. The purpose of this study was to determine the pharmacokinetics of altrenogest following PO or per rectum (PR) administration in mares. Using a randomized two-way crossover study design, six horses received altrenogest (...
Haddad NS, Pedersoli WM, Ravis WR, Fazeli MH, Carson RL.Healthy mature pony mares (n = 6) were given a single dose of gentamicin (5 mg/kg of body weight) IV or IM 8 days apart. Venous blood samples were collected at 0, 5, 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, 30, 36, 40, and 48 hours after IV injection of gentamicin, and at 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, and 30 hours after IM injection of gentamicin. Gentamicin serum concentration was determined by a liquid-phase radioimmunoassay. The combined data of IV and IM treatments were analyzed by a nonlinear least-square...
Haddad NS, Pedersoli WM, Ravis WR, Fazeli MH, Carson RL.Gentamicin (GT) was administered IM to 6 healthy mature mare ponies at a dosage of 5 mg/kg of body weight every 8 hours for 7 consecutive days (total, 21 doses). Two venous blood samples were collected before (trough) and at 1 hour (peak) after the 5th, 10th, 14th, and 19th doses. An endometrial biopsy was done of each mare on days 4 and 7. On the 7th day, just before the 21st administration of GT, base-line blood samples were collected, and 22 blood samples were collected over a period of 48 hours after GT was given. The mares were catheterized on the 7th day, and urine was collected for 24 h...
Thevis M, Opfermann G, Schänzer W.Electrospray ionization (ESI) mass spectra of 19 common beta(2)-agonists were investigated in terms of fragmentation pattern and dissociation behavior of the analytes, proving the origin of fragment ions and indicating mechanisms of charge-driven and charge-remote fragmentation. Based on these data, liquid chromatographic/ESI tandem mass spectrometric (LC/ESI-MS/MS) screening and confirmation methods were developed for doping control purposes. These procedures employ established sample preparation steps including either acidic or enzymatic hydrolysis, alkaline extraction and, in the case of eq...
Young LE, Blissitt KJ, Clutton RE, Molony V.To evaluate temporal hemodynamic effects of dobutamine in horses anesthetized with halothane. Methods: 8 adult Thoroughbreds. Methods: Anesthesia was induced by i.v. administration of romifidine and ketamine and maintained using halothane in oxygen. After 60 minutes, dobutamine was administered i.v. for 60 minutes at 4 micrograms/kg of body weight/min. Measurements of left ventricular function were obtained by transesophageal echocardiography and cardiac catheterization. Results: Mean, systolic, diastolic, aortic, pulmonary arterial, and left and right ventricular end-diastolic and systolic pr...
Oreff GL, Tatz AJ, Dahan R, Segev G, Haberman S, Britzi M, Kelmer G.To determine the metacarpophalangeal joint fluid concentrations of ceftazidime administered via regional limb perfusion (RLP). Methods: Eight healthy horses. Methods: RLP was performed by injecting 2 g of ceftazidime and 60 mL of perfusate volume in the cephalic vein of standing, sedated horses. Serum and synovial fluid from the metacarpophalangeal joint were collected before perfusion and at 0.5, 2, 6, 12, 24 hours postperfusion. Ceftazidime concentrations were measured via liquid chromatography. Maximal concentration (C ), area under the curve (AUC), half-life of the drug (T ½), and the tim...
Thevis M, Opfermann G, Krug O, Schänzer W.Isotope-dilution mass spectrometry has been employed successfully in numerous fields of analytical chemistry enabling the establishment of fast and reliable procedures. In equine sports, xanthine derivatives such as caffeine and theobromine are prohibited, and doping control laboratories analyze horse urine specimens regarding these illicit performance-enhancing drugs. Theobromine has to exceed a threshold level of 2 microg/mL, hence a robust and reliable quantitation is required. Stably deuterated theobromine and caffeine were synthesized by the reaction of xanthine or theobromine with iodome...
Bailly-Chouriberry L, Noguier F, Manchon L, Piquemal D, Garcia P, Popot MA, Bonnaire Y.Recombinant human erythropoietins (rHuEPOs) are glycoproteins drugs, produced by the pharmaceutical industry to restore production of red blood cells by stimulating human bone marrow for which this pathology has been diagnosed. It is suspected that these molecules are diverted as doping agents in horseracing to enhance oxygen transport and aerobic power in racehorses. Although indirect double-blotting or direct liquid chromatography-mass spectrometry (LC-MS) methods have been developed to confirm the presence of rHuEPO in a sample, the short detection time (48 h) is still a problem for doping ...
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...
Knych HK, Mama KR, Moore CE, Hill AE, McKEMIE DS.The use of intra-articular (IA) local anaesthetics has proven to be an effective means to treat post-operative pain. The effects of local anaesthetics on equine chondrocytes are mixed with some studies reporting chondrodestruction and others no adverse effects. A liposomal formulation of bupivacaine is used in people and dogs by intra- and peri-articular administration to provide up to 72 h of analgesia. The potential uses, side effects including chondrotoxicity, and likelihood of abuse (long-term analgesic effects) has not been evaluated in horses. Objective: Describe bupivacaine concentrati...
Jöchle W.In this uncontrolled clinical study 12 investigators cooperated to evaluate the analgesic and sedative effect of detomidine (DORMOSEDAN; Farmos Group Ltd; Finland) in 234 horses with abdominal pain caused by colic. The study was designed to use each animal as its own control and to evaluate its response to the drug over a 60 min period. Detomidine was given intravenously (i.v.) once in 169 cases (167 horses, 1 mule, 1 donkey) at a dose of 20 micrograms/kg bodyweight (bwt), and to 65 horses at 40 micrograms/kg bwt. The higher dose was used predominantly in horses with severe pain which were mor...
Kutscha J, Sutton DG, Preston T, Guthrie AJ.Imidocarb dipropionate is the drug of choice for equine piroplasmosis but its administration causes severe colic and diarrhoea. An imidocarb protocol that reduces these effects is needed. Objective: 1) Quantification of the effects of imidocarb dipropionate on equine orocaecal transit time (OCTT), with and without atropine or glycopyrrolate premedication and 2) investigation of an improved pretreatment regimen for imidocarb administration. Objective: Treatment with imidocarb dipropionate will result in colic and reduced OCTT as demonstrated by the lactose 13C-ureide breath test which will be a...
Prescott JF, Hoover DJ, Dohoo IR.The pharmacokinetic parameters of erythromycin in foals were determined following intravenous administration of 5.0 mg/kg to animals aged 1, 3, 5 and 7 weeks. The distribution of the drug was described by a two-compartment open model, and no significant differences were observed between coefficients on which the parameters were based. Pharmacokinetic values were also determined for four mares given 5.0 mg/kg intravenously and for six 10-12-week-old foals given 20.0 mg/kg intravenously. The half-life of erythromycin for all groups of animals (foals less than 7 weeks, mares, foals 10-12 weeks) w...
Hubbell JA, Muir WW, Sams RA.We determined the cardiopulmonary changes in horses given guaifenesin alone and in the same horses given xylazine (IV) immediately before administration of guaifenesin. In addition, plasma guaifenesin concentrations were determined in horses and 2 pregnant mares and compared with previously published values in ponies. The dose of guaifenesin necessary to produce lateral recumbency in adult horses was 134 +/- 34 mg/kg (mean +/- SD). The administration of guaifenesin caused insignificant (P less than 0.05) changes in heart rate, respiratory rate, right atrial pressure, pulmonary arterial pressur...
Zantingh AJ, Schwark WS, Fubini SL, Watts AE.To determine the effect of regional limb perfusion (RLP) with amikacin sulfate alone and in combination with ticarcillin/clavulanate on synovial fluid concentration and antimicrobial activity of amikacin. Methods: Experimental study. Methods: RLP with amikacin alone (A; 2.5 g) or amikacin and ticarcillin/clavulanate (AT; 2.5 g amikacin, 7 g ticarcillin/clavulanate) was performed with a tourniquet placed at mid-antebrachium in standing, sedated horses. Perfusate blood was collected immediately after injection and again before tourniquet release. Blood from the jugular vein was collected before ...
Loganathan D, Yi R, Patel B, Zhang J, Kong N.Resolution of cathinone enantiomers in equine anti-doping analysis is becoming more important to distinguish the inadvertent ingestion of plant-based products from those of deliberate administration of designer synthetic analogs. With this in mind, a rapid and sensitive method was developed and validated for the detection, resolution and quantitative determination of cathinone enantiomers in horse blood plasma and urine. The analytes were recovered from the blood plasma and urine matrices by using a liquid-liquid extraction after adjusting the pH to 9. The recovered analytes were derivatized w...
Boscan P, Van Hoogmoed LM, Pypendop BH, Farver TB, Snyder JR.To determine the pharmacokinetics and effects of the morphine antagonist N-methylnaltrexone (MNTX) on gastrointestinal tract function in horses when administered alone and in combination with morphine. Methods: 5 healthy adult horses. Methods: Horses were treated with MNTX (1 mg/kg, IV), and serial blood samples were collected for determination of drug pharmacokinetics. For evaluation of effects on the gastrointestinal tract when administered alone, MNTX was administered at a dosage of 0.75 mg/kg, IV, twice daily for 4 days. For evaluation of effects when administered concurrently with morphin...
Riggs CM, Thompson SL, So YM, Wong JKY, Wan TSM, Robinson P, Stewart BD, Ho ENM.Administration of bisphosphonates, including tiludronic acid, to Thoroughbred racehorses below 3 and a half years of age is prohibited in most racing jurisdictions. Objective: To determine if evidence of administration of tiludronic acid could be obtained from analysis of blood and urine samples beyond 40 days after administration. Methods: Retrospective cohort. Methods: Horses maintained in a highly controlled environment and treated with Tildren®a were selected from clinical records. Twenty-four horses were identified, 21 of which were still in race training. Blood and urine samples were c...
Spehar AM, Hill MR, Mayhew IG, Hendeles L.Pharmacokinetic characteristics of the anticonvulsant phenobarbital were studied in seven pony and two Thoroughbred foals aged between four and 10 days. A single, 20 mg/kg bodyweight (bwt) dose of phenobarbital was given intravenously over 25 mins and the serum concentrations of the drug were measured using an EMIT AED assay (coefficient of variation 1.37 per cent at 30 micrograms/ml, n = 7). Phenobarbital elimination was found to follow first order kinetics. The mean (+/- sd) peak phenobarbital serum concentration was 18.6 +/- 2.1 micrograms/ml at 1 h after initiation of infusion with a mean ...
Markell R, Saviola G, Barker EA, Conway JD, Dujardin C.There has recently been some controversy over the use of bisphosphonates in horses and some confusion regarding the different classes of bisphosphonates and the differences between the mechanism of actions and effects of each class. This review article explores the different bisphosphonate classes and their different effects and mechanisms of action based on research from both the human and equine veterinary fields. This collaborative review between veterinary surgeons and medical doctors describes the latest use of bisphosphonates in humans and horses, including safety aspects, and allows com...
Brown MP, Kelly RH, Stover SM, Gronwall R.Six healthy adult mares were given a single IV injection of trimethoprim (TMP)-sulfadiazine (SDZ) at a dosage rate of 2.5 mg of TMP/kg of body weight and 12.5 mg of SDZ/kg. Serum, synovial, peritoneal, and urine TMP-SDZ concentrations were measured serially over a 48-hour period. The highest measured mean concentrations of TMP and SDZ were found in the first (0.5 hour) sample of serum, synovial fluid, and peritoneal fluid. The mean peak concentrations of TMP and SDZ averaged 4.37 micrograms/ml and 21.81 micrograms/ml for serum, 2.95 micrograms/ml and 15.31 micrograms/ml for synovial fluid, and...
Guan F, You Y, Fay S, Li X, Robinson MA.To address the limitations of current targeted analytical methods that can only detect known doping agents, a novel methodology that permits untargeted drug detection (UDD) has been developed to help in the fight against doping in sports. Fifty-seven drugs were spiked into blank equine plasma and were treated as unknowns since their exact masses and chromatographic retention times were not utilized for detection. The spiked drugs were extracted from the plasma samples and were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). The acquired LC-HRMS raw ...
