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.
Zullian C, Menozzi A, Pozzoli C, Poli E, Bertini S.The effects of selective α(2)-agonists (xylazine, detomidine and medetomidine) and antagonists (yohimbine and atipamezole) on in vitro small intestine motility in the horse were evaluated. Samples of equine jejunum were placed in isolated organ baths and drug-induced modifications of motility were measured by means of an isotonic transducer. All tested α(2)-agonists dose-dependently reduced both spontaneous and electrically-evoked phasic contractions. Conversely, α(2)-antagonists were ineffective when tested alone, and showed a heterogeneous and dose-independent ability to inhibit agonist a...
Kwok WH, Leung DK, Leung GN, Wan TS, Wong CH, Wong JK.A rapid liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed for the simultaneous screening of 19 drugs of different classes in equine plasma using automated on-line solid-phase extraction (SPE) coupled with a triple quadrupole mass spectrometer. Plasma samples were first protein precipitated using acetonitrile. After centrifugation, the supernatant was directly injected into the on-line SPE system and analysed by a triple quadrupole LC-MS-MS in positive electrospray ionisation (+ESI) mode with selected reaction monitoring (SRM) scan function. On-line extraction and c...
Rojer H, Aurich C.Recently, successful treatment of mares with a history of persistent mating-induced endometritis (PMIE) with dexamethasone has been reported. As systemic treatment of horses with glucocorticoids should be handled with caution, we tested the hypothesis that treatment with the non-steroid anti-inflammatory drug (NSAID) vedaprofen, an inhibitor of cyclooxygenase-2, may have comparative, positive effects on fertility. Barren mares with a history of repeated PMIE were treated with vedaprofen (n = 8; initially 2 mg/kg bodyweight followed by 1 mg/kg orally twice daily) from 1 day before the first ins...
Levionnois OL, Mevissen M, Thormann W, Spadavecchia C.The objective of this study was to assess a pharmacokinetic algorithm to predict ketamine plasma concentration and drive a target-controlled infusion (TCI) in ponies. Firstly, the algorithm was used to simulate the course of ketamine enantiomers plasma concentrations after the administration of an intravenous bolus in six ponies based on individual pharmacokinetic parameters obtained from a previous experiment. Using the same pharmacokinetic parameters, a TCI of S-ketamine was then performed over 120 min to maintain a concentration of 1 microg/mL in plasma. The actual plasma concentrations of ...
Boscan P, Rezende ML, Grimsrud K, Stanley SD, Mama KR, Steffey EP.To define the pharmacokinetic profile of propofol 5% microemulsion formulation in horses. Methods: First, propofol was administered as bolus injection (2 mg kg(-1)) to six xylazine-sedated horses. Secondly, after sedation and bolus injection, propofol was maintained with continuous infusion for 3 h [8.1 (sd 3.2) mg kg(-1) h(-1)] to the same six horses. Thirdly, in two horses, a commercial propofol was used for comparison. Response to noxious stimulation was used to evaluate analgesia. Venous blood samples were obtained to measure propofol plasma concentration using liquid chromatography-mass s...
Houghton E, Maynard S.This chapter reviews drug and medication control in equestrian sports and addresses the rules of racing, the technological advances that have been made in drug detection and the importance of metabolism studies in the development of effective drug surveillance programmes. Typical approaches to screening and confirmatory analysis are discussed, as are the quality processes that underpin these procedures. The chapter also addresses four specific topics relevant to equestrian sports: substances controlled by threshold values, the approach adopted recently by European racing authorities to control...
Tsujimura K, Yamada M, Nagata S, Yamanaka T, Nemoto M, Kondo T, Kurosawa M, Matsumura T.We investigated the pharmacokinetics of penciclovir after oral administration of its prodrug famciclovir to horses. Following an oral dose of famciclovir at 20 mg/kg, maximum plasma concentrations of penciclovir occurred between 0.75 and 1.5 hr (mean 0.94 + or - 0.38 hr) after dosing and were in the range 2.22 to 3.56 microg/ml (mean 2.87 + or - 0.61 microg/ml). The concentrations of penciclovir declined in a biphasic manner after the peak concentration was attained. The mean half-life of the rapid elimination phase was 1.73 + or - 0.34 hr whereas that of the slow elimination phase was 34.34 +...
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...
Frost AB, Larsen F, Larsen SW, Østergaard J, Thomsen MH, Stürup S, Andersen PH, Larsen C.To establish a pharmacokinetic model for the model drug, sodium diatrizoate (DTZ), allowing joint disappearance kinetics to be estimated from serum appearance kinetics following intra-articular administration, and to calculate the relative joint exposure after intravenous and intra-articular DTZ administration (F(iv/IA)). Methods: Each of five horses received an aqueous solution of 3.9 mg/kg sodium diatrizoate both intravenously and intra-articularly separated by a one-week wash out period. Serum and synovial samples were collected over 7 h and analyzed for content of model compound using indu...
Kelmer G, Catasus CT, Saxton AM, Elliot SB.The feasibility of maintaining indwelling intravenous catheters in the saphenous, cephalic or palmar digital vein of horses for seven days to infuse antimicrobial drugs was investigated in 18 horses. The horses were randomly assigned to six groups according to the vein catheterised and whether they received amikacin or erythromycin. None of the catheters was replaced more than once, and 11 of the 18 catheters remained patent for all seven days. Neither the drug administered nor the vein catheterised significantly affected the survival of the catheter. In all but three cases, complications, inc...
Dhanjal JK, Wilson DV, Robinson E, Tobin TT, Dirikolu L, Dirokulu L.To determine the optimal dose, serum concentrations and analgesic effects of intravenous (IV) tramadol in the horse. Two-phase blinded, randomized, prospective crossover trial. Seven horses (median age 22.5 years and mean weight 565 kg). Horses were treated every 20 minutes with incremental doses of tramadol HCl (0.1-1.6 mg kg(-1)) or with saline. Heart rate, respiratory rate, step frequency, head height, and sweating, trembling, borborygmus and head nodding scores were recorded before and up to 6 hours after treatment. In a second study, hoof withdrawal and skin twitch reflex latencies (HWRL ...
Chuang MS, Huang HH, Dixon KM, Chen KS, Mao CL, Chen CL.The pharmacokinetics of clenbuterol in equine urine and blood was investigated. Methods: Urine and blood samples were collected following 3-day multiple oral administrations. The samples were examined using enzyme-linked immunosorbent assay and further confirmed by solid phase extraction and capillary electrophoresis. Results: Urinary clenbuterol was detectable until day 14 after the last dose. The urinary excretion of clenbuterol was characterized by a biphasic pattern. The half-lives of the bi-exponential elimination (t(1/2alpha) and t(1/2beta)) for urinary clenbuterol were about 12.1 and 48...
Ferrante M, Andreeta A, Landoni MF.Diclofenac is a hydrophilic non-steroidal anti-inflammatory drug widely used in humans and animals. Previous reports have shown that this compound has low percutaneous absorption in horses. The effect of five penetration enhancers (10% urea, 15% and 20% oleic acid and 5% and 10% d-limonene) on the percutaneous absorption of diclofenac diethylamine through horse skin was evaluated in vitro using Franz-type diffusion cells. All tested penetration enhancers induced a significant increase in diclofenac diethylamine permeation, with limonene showing the highest enhancing effect at the lowest concen...
Muir WW, Lerche P, Erichson D.Studies have demonstrated the clinical usefulness of propofol for anaesthesia in horses but the use of a concentrated solution requires further investigation. Objective: To determine the anaesthetic and cardiorespiratory responses to a bolus injection of 10% propofol solution in mature horses. Methods: Three randomised crossover experimental trials were completed. Trial 1: 6 horses were selected randomly to receive 10% propofol (2, 4 or 8 mg/kg bwt i.v.). Trial 2: 6 horses received 1.1 mg/kg bwt i.v. xylazine before being assigned at random to receive one of 5 different doses (1-5 mg/kg bwt) o...
Nielsen MK.Given the increasing levels of anthelmintic resistance in equine parasites, parasitologists now recommend traditional treatment approaches to be abandoned and replaced by more sustainable strategies. It is of crucial importance to facilitate veterinary involvement to ensure that treatment decisions are based on parasitic knowledge. Despite recommendations given for the past two decades, strategies based on the selective therapy principle have not yet been implemented on a larger scale in equine establishments. In contrast, treatment regimens appear to be derived from recommendations originally...
Cobb R, Boeckh A.This article reviews the current knowledge of the use of moxidectin (MOX) in horses, including its mode of action, pharmacokinetic and pharmacodynamic properties, efficacy, safety and resistance profile.Moxidectin is a second generation macrocyclic lactone (ML) with potent endectocide activity. It is used for parasite control in horses in an oral gel formulation. The principal mode of action of MOX and of other MLs is binding to gamma-aminobutyric (GABA) and glutamate-gated chloride channels. Moxidectin is different from other MLs in that it is a poor substrate for P-glycoproteins (P-gps) and ...
Linardi RL, Stokes AM, Barker SA, Short C, Hosgood G, Natalini CC.Methadone hydrochloride is a synthetic mu-opioid receptor agonist with potent analgesic properties. Oral methadone has been successfully used in human medicine and may overcome some limitations of other analgesics in equine species for producing analgesia with minimal adverse effects. However, there are no studies describing the pharmacokinetics (PK) of oral opioids in horses. The aim of this study was to describe the PK of orally administered methadone (0.1, 0.2 and 0.4 mg/kg) and physical effects in 12 healthy adult horses. Serum methadone concentrations were measured by gas chromatography/m...
Pearce JW, Giuliano EA, Moore CP.To evaluate and compare the in vitro susceptibility of Aspergillus and Fusarium spp. isolated from horses with ulcerative keratomycosis, address regional differences in equine keratomycosis isolates, and provide susceptibility data to update prior studies. Methods: Fourteen horses with ulcerative keratomycosis. Methods: Banked fungal isolates from equine corneal ulcers (eight Aspergillus spp. and six Fusarium spp.) were identified at The University of Texas Health Science Center at San Antonio. In vitro minimum inhibitory concentration and susceptibility to natamycin, fluconazole, itraconazole...
Vonaparti A, Lyris E, Panderi I, Koupparis M, Georgakopoulos C.In equine sport, salicylic acid is prohibited with a threshold level of 750 microg mL(-1) in urine; hence, doping control laboratories have to establish quantitative and qualitative methods for its determination. A simple and rapid liquid chromatographic/mass spectrometric method was developed and validated for the quantification and identification of salicylic acid. Urine samples after 900-fold dilution and addition of the internal standard (4-methylsalicylic acid) were directly injected to the liquid chromatography/quadrupole time-of-flight mass spectrometry system. Electrospray ionization i...
Singh BR.Vancomycin resistant and multi-drug-resistant enterococci are the major emerging pathogens in surgical, neonatal, and tertiary care units. Methods: In this study, 267 enterococci from different clinical and non-clinical samples of equine origin were tested for their antimicrobial drug sensitivity against 19 antimicrobials using disc diffusion method. Results: A total of 80.2% enterococci tested were resistant to vancomycin and 99.6% to multiple-drugs. There was a significant association between haemolytic potential and vancomycin resistance (chi(2), 0.00). Enterococci isolates from healthy equ...
Brosnan RJ, Steffey EP.We hypothesized that propofol can produce rapidly-reversible, dose-dependent standing sedation in horses. Methods: Prospective randomized, blinded, experimental trial. Methods: Twelve healthy horses aged 12 +/- 6 years (mean +/- SD), weighing 565 +/- 20 kg, and with an equal distribution of mares and geldings. Methods: Propofol was administered as an intravenous bolus at one of three randomized doses (0.20, 0.35 and 0.50 mg kg(-1)). Cardiovascular and behavioral measurements were made by a single investigator, who was blinded to treatment dose, at 3 minute intervals until subjective behavior s...
Steffey EP, Mama KR, Brosnan RJ, Imai A, Maxwell LK, Cole CA, Stanley SD.To compare characteristics of horses recovering from 4 hours of desflurane anesthesia with and without immediate postanesthetic IV administration of propofol and xylazine. Animals-8 healthy horses (mean +/- SEM age, 6.6 +/- 1.0 years; mean body weight, 551 +/- 50 kg). Methods: Horses were anesthetized twice. Both times, anesthesia was induced with a combination of xylazine hydrochloride, diazepam, and ketamine hydrochloride and then maintained for 4 hours with desflurane in oxygen. Choice of postanesthetic treatment was randomly assigned via a crossover design such that each horse received an ...
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...
Dirikolu L, Karpiesiuk W, Lehner AF, Hughes C, Granstrom DE, Tobin T.Triazine-based antiprotozoal agents are known for their lipophylic characteristics and may therefore be expected to be well absorbed following oral administration. However, although an increase in lipid solubility generally increases the absorption of chemicals, extremely lipid-soluble chemicals may dissolve poorly in gastrointestinal (GI) fluids, and their corresponding absorption and bioavailability would be low. Also, if the compound is administered in solid form and is relatively insoluble in GI fluids, it is likely to have limited contact with the GI mucosa, and therefore, its rate of abs...
Doherty TJ.Surgical manipulation of the intestines activates intestinal macrophages that release cytokines and nitric oxide, which results in inhibition of intestinal motility. Subsequent infiltration of circulating leukocytes into the intestinal wall contributes to cytokine and nitric oxide release and exacerbates ileus. Other factors contributing to ileus are endotoxemia; edema of the intestine wall subsequent to excessive fluid therapy; hypocalcemia; and long abdominal incisions. Because treatment of ileus with prokinetic drugs has not proven to be very effective, efforts should be directed at reducin...
Larenza MP, Peterbauer C, Landoni MF, Levionnois OL, Schatzmann U, Spadavecchia C, Thormann W.To evaluate pharmacokinetics of ketamine and norketamine enantiomers after constant rate infusion (CRI) of a subanesthetic dose of racemic ketamine or S-ketamine in ponies. Methods: Five 6-year-old Shetland pony geldings that weighed between 101 and 152 kg. Methods: In a crossover study, each pony received a CRI of racemic ketamine (loading dose, 0.6 mg/kg; CRI, 0.02 mg/kg/min) and S-ketamine (loading dose, 0.3 mg/kg; CRI, 0.01 mg/kg/min), with a 1-month interval between treatments. Arterial blood samples were collected before and at 5, 15, 30, 45, and 60 minutes during drug administration and...
Grimsrud KN, Mama KR, Thomasy SM, Stanley SD.Detomidine is commonly used i.v. for sedation and analgesia in horses, but the pharmacokinetics and metabolism of this drug have not been well described. Objective: To describe the pharmacokinetics of detomidine and its metabolites, 3-hydroxy-detomidine (OH-detomidine) and detomidine 3-carboxylic acid (COOH-detomidine), after i.v. and i.m. administration of a single dose to horses. Methods: Eight horses were used in a balanced crossover design study. In Phase 1, 4 horses received a single dose of i.v. detomidine, administered 30 microg/kg bwt and 4 a single dose i.m. 30 microg/kg bwt. In Phase...
McKinney AR.Control of the use of performance-affecting substances in the horse is critical to the integrity of a wide range of equine sports, with major implications for both animal welfare and revenue streams. One class of medications enjoying particular public notoriety is the anabolic-androgenic steroid group, as highlighted by the recent 'Big Brown' affair and Congressional inquiries into the use of steroids in professional sports, including horse racing, in the USA. This review examines the latest developments pertaining to the analytical detection of these substances in equine biological samples an...
Rohrbach H, Korpivaara T, Schatzmann U, Spadavecchia C.To evaluate and compare the antinociceptive effects of the three alpha-2 agonists, detomidine, romifidine and xylazine at doses considered equipotent for sedation, using the nociceptive withdrawal reflex (NWR) and temporal summation model in standing horses. Methods: Prospective, blinded, randomized cross-over study. Methods: Ten healthy adult horses weighing 527-645 kg and aged 11-21 years old. Methods: Electrical stimulation was applied to the digital nerves to evoke NWR and temporal summation in the left thoracic limb and pelvic limb of each horse. Electromyographic reflex activity was reco...
Nourian AR, Mills PC, Pollitt CC.Intraosseous (i.o.) infusion of the distal phalanx (IOIDP) as a delivery route targeting hoof lamellar tissue of standing, conscious horses was evaluated. Following sedation and regional nerve blockade in six Standardbred horses, a microdialysis (MD) probe was implanted into the hoof lamellar tissue of one forelimb. A purpose designed cannulated bone screw was introduced into the body of the distal phalanx, approximately 6 cm from the MD probe. Gentamicin solution (25 mg/mL) was infused at 20 microL/min through the bone screw for 2 h without the application of a tourniquet. MD and blood sample...
Wieder ME, Paine SW, Hincks PR, Pearce CM, Scarth J, Hillyer L.Salbutamol sulphate (Ventolin Evohaler) was administrated via the inhalation route to six horses at a dose of 0.5 mg every 4 h during the day for 2 days (total dose 4 mg). Urine and blood samples were taken up to 92 h postadministration. Hydrolyzed plasma and urine were extracted using solid phase extraction (SPE). A sensitive tandem mass spectrometric method was developed in this study, achieving a lower limit of quantification (LLOQ) for salbutamol of 10 pg/mL in plasma and urine. The parent drug was identified using UPLC-MS/MS. Most of the determined salbutamol plasma concentrations, post l...
Shane SE, Langston VC, Wills RW, Denney WS, Knych H, Fontenot RL, Meyer RE, Natalini CC.An ideal dexmedetomidine protocol has yet to be determined for standing sedation in horses. It was hypothesized that an IV bolus followed by CRI dexmedetomidine would have a quicker increase in plasma concentrations compared with repeated IM injections. In a crossover design, eight adult, female horses were randomly placed into two groups: the CRI group (IV bolus dexmedetomidine at 0.005 mg/kg followed by a CRI at 0.01 mg/kg/h for 15 min then 0.005 mg/kg/h for 60 min) and the IM group (dexmedetomidine at 0.01 mg/kg, followed by 0.005 mg/kg in 30-min intervals for 60 min). Clearance and...
Clarke A, Scarth J, Teale P, Pearce C, Hillyer L.Detection of androgenic-anabolic steroid abuse in equine sports requires knowledge of the drug's metabolism in order to target appropriate metabolites, especially where urine is the matrix of choice. Studying 'designer' steroid metabolism is problematic since it is difficult to obtain ethical approval for in vivo metabolism studies due to a lack of toxicological data. In this study, the equine in vitro metabolism of eight steroids available for purchase on the Internet is reported; including androsta-1,4,6-triene-3,17-dione, 4-chloro,17α-methyl-androsta-1,4-diene-3,17β-diol, estra-4,9-diene-...
De Clercq D, Baert K, Croubels S, van Loon G, Maes A, Tavernier R, Deprez P, De Backer P.To determine the clinical effects and pharmacokinetics of amiodarone after single doses of 5 mg/kg administered orally or intravenously. Methods: 6 healthy adult horses. Methods: In a cross over study, clinical signs and electrocardiographic variables were monitored and plasma and urine samples were collected. A liquid chromatography-mass spectrometry method was used to determine the percentage of protein binding and to measure plasma and urine concentrations of amiodarone and the active metabolite desethylamiodarone. Results: No adverse clinical signs were observed. After IV administration, m...
van Duijkeren E, Vulto AG, Sloet van Oldruitenborgh-Oosterbaan MM, Kessels BG, van Miert AS, Breukink HJ.In the present study, the pharmacokinetic parameters of a trimethoprim/sulphachlorpyridazine preparation following intravenous administration, administration by nasogastric tube and administration with concentrate were determined in the horse. Eight adult horses were dosed at 1 week intervals in a sequentially designed study at a dose of 5 mg/kg trimethoprim (TMP) and 25 mg/kg sulphachlorpyridazine (SCP) on all occasions. Plasma concentrations of both drugs were measured serially for 48 h. Pharmacokinetic parameters of clinical importance (distribution and elimination half-lives, clearance, bi...
Ensink JM, Vulto AG, van Miert AS, Tukker JJ, Winkel MB, Fluitman MA.To determine the oral bioavailabilities of 3 ampicillin esters (pivampicillin, bacampicillin, and talampicillin) and ampicillin sodium, and to determine in vitro stability of the ampicillin esters in ileal contents (pH 8.3 to 8.5). Methods: A crossover design to administer the 4 drugs orally, and ampicillin i.v. to all horses in the study. Methods: 4 healthy adult horses. Methods: The drugs were administered intragastrically to the horses at a dosage equimolar to 15 mg of ampicillin/kg of body weight. Also, ampicillin sodium was administered i.v. at the same dosage. Blood samples were taken up...
Winther L, Baptiste KE, Friis C.Ampicillin concentrations in pulmonary epithelial lining fluid (PELF) and plasma was studied after single intravenous ampicillin administration (15mg/kg) or single intragastric administration of its prodrug, pivampicillin (19.9mg/kg) to horses and discussed in relation to minimum inhibitory concentrations (MIC) of common equine respiratory pathogens. After intravenous administration, elimination of ampicillin was fast and not detectable in plasma after 12h in three out of six horses. Pivampicillin was absorbed well in non-fasted horses with an oral bioavailability of 36%. The degree of penetra...
Knych HK, Harrison LM, White A, McKemie DS.The use of isoflupredone acetate in performance horses and the scarcity of published pharmacokinetic data necessitate further study. The objective of the current study was to describe the plasma pharmacokinetics of isoflupredone acetate as well as time-related urine and synovial fluid concentrations following intra-articular administration to horses. Twelve racing-fit adult Thoroughbred horses received a single intra-articular administration (8 mg) of isoflupredone acetate into the right antebrachiocarpal joint. Blood, urine and synovial fluid samples were collected prior to and at various tim...
Ingvast-Larsson C, Appelgren LE, Nyman G.After intravenous administration of theophylline, microdialysis has been used for studying the non protein bound theophylline concentration in blood and in lung tissue in the rat as well as in two horses. The distribution pattern of 14C-theophylline in the rat was also investigated. When the distribution of theophylline was completed the time course of free drug in the interstitial fluid in lung tissue was in good agreement with the total concentration-time profile in plasma in both species. In the rat the free concentration of theophylline in the lung was slightly lower than the free concentr...
Serrano-Rodríguez JM, Gómez-Díez M, Esgueva M, Castejón-Riber C, Mena-Bravo A, Priego-Capote F, Ayala N, Caballero JMS, Muñoz A.Pharmacokinetic and pharmacodynamic (PK/PD) properties of the angiotensin-converting enzyme inhibitor (ACEI) benazeprilat have not been evaluated in horses. This study was designed to establish PK profiles for benazepril and benazeprilat after intravenous (IV) and oral (PO) administration of benazepril using a PK/PD model. This study also aims to determine the effects of benazeprilat on serum angiotensin converting enzyme (ACE), selecting the most appropriate dose that suppresses ACE activity. Six healthy horses in a crossover design received IV benazepril at 0.50mg/kg and PO at doses 0 (place...
Current drug metabolismAugust 27, 2022
Volume 23, Issue 10 850-865 doi: 10.2174/1389200223666220825093945
Ishii H, Shibuya M, Kusano K, Sone Y, Kamiya T, Wakuno A, Ito H, Miyata K, Sato F, Kuroda T, Yamada M, Leung GN.Vadadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitor, is a substance which carries a lifetime ban in both horse racing and equestrian competition. A comprehensive metabolic study of vadadustat in horses has not been previously reported. Objective: Metabolism and elimination profiles of vadadustat in equine plasma and urine were studied for the purpose of doping control. Methods: A nasoesophageal administration of vadadustat (3 g/day for 3 days) was conducted on three thoroughbred mares. Potential metabolites were comprehensively detected by differential analysis of ful...
Kwok WH, Choi TL, So PK, Yao ZP, Wan TS.Xenon can activate the hypoxia-inducible factors (HIFs). As such, it has been allegedly used in human sports for increasing erythropoiesis. Krypton, another noble gas with reported narcosis effect, can also be expected to be a potential and less expensive erythropoiesis stimulating agent. This has raised concern about the misuse of noble gases as doping agents in equine sports. The aim of the present study is to establish a method for the simultaneous detection of xenon and krypton in equine plasma for the purpose of doping control. Xenon- or krypton-fortified equine plasma samples were prepar...
Elsener J, Villeneuve A.The impact of a late fall treatment on the spring rise of fecal egg counts was evaluated in a controlled study with Canadian horses treated with 2 different dewormers immediately after removal from pasture for winter housing. The horses were stabled until the end of the trial period. Seventeen weanlings, 20 yearlings, and 15 2-year-old horses located in Ontario, which were presumed to be naturally infected with cyathostomins after pasture grazing, were randomly allocated to either a group treated with 0.4 mg/kg of moxidectin and 2.5 mg/kg of praziquantel or a group treated with 0.2 mg/kg of iv...
Soma LR, Robinson MA, You Y, Boston RC, Rudy J.Compartmental models were used to investigate the pharmacokinetics of intravenous (i.v.), oral (p.o.), and topical (TOP) administration of dimethyl sulfoxide (DMSO). The plasma concentration-time curve following a 15-min i.v. infusion of DMSO was described by a two-compartment model. Median and range of alpha (t ) and beta (t ) half-lives were 0.029 (0.026-0.093) and 14.1 (6.6-16.4) hr, respectively. Plasma concentration-time curves of DMSO following p.o. and TOP administration were best described by one-compartment absorption and elimination models. Following the p.o. administration, median a...
Kuroda T, Nagata S, Takizawa Y, Tamura N, Kusano K, Mizobe F, Hariu K.The pharmacokinetics of d-chlorpheniramine (CPM), a histamine H1-receptor antagonist, and its ability to inhibit of histamine-induced cutaneous wheal formation, were studied in healthy Thoroughbred horses (n=5). Following an intravenous (IV) dose of 0.5mg/kg bodyweight (BW), plasma drug disposition was very rapid, with the mean terminal half-life and total body clearance calculated as 2.7h and 0.7 L/h/kg, respectively. The observed maximal inhibition of wheal formation following IV doses of 0.1 and 0.5mg/kg BW were 37.8% and 60.6% at 0.5h, respectively. Oral administration of CPM (0.5mg/kg BW)...
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...
Marchiondo AA, White GW, Smith LL, Reinemeyer CR, Dascanio JJ, Johnson EG, Shugart JI.Clinical field trials were conducted at five geographical locations in the USA (Oklahoma, Wisconsin, Tennessee, Virginia and Idaho) to evaluate the efficacy and safety of pyrantel pamoate paste (19.13%, w/w, pyrantel base) administered at the recommended dosage of 13.2 mg pyrantel base/kg (6.0 mg pyrantel base/lb) body weight (b.w.) against tapeworm infections of Anoplocephala spp. in naturally infected horses. Horses at each study site were allocated by restricted randomization based on the cestode status (positive or negative) of pre-treatment fecal egg counts to complete sets of four animal...
Habershon-Butcher J, Cutler C, Viljanto M, Hincks PR, Biddle S, Paine SW.Xylazine is widely used worldwide as a short-acting sedative in general equine and racing practice. In the UK, although it has a legitimate use during training, equine anti-doping rules state it is a prohibited substance on race day. The aim of the study was to produce a detection time (DT) to better inform European veterinary surgeons so that xylazine can be used appropriately under regulatory rules. Previous publications have various limitations pertaining to analysis method, particularly for plasma and limited length of time of sample collection. In this study, pharmacokinetic data were pro...
González G, Ventura R, Smith AK, de la Torre R, Segura J.A gas chromatographic-mass spectrometric (GC-MS) procedure for the detection of seventeen non-steroidal anti-inflammatory drugs (NSAIDs) in equine plasma and urine samples is described. The extraction of the compounds from the biological matrix was performed at acidic pH (2-3) with diethyl ether. Ethereal extracts were washed with a saturated solution of sodium hydrogencarbonate (urine) or treated with a solid mixture of sodium carbonate and sodium hydrogencarbonate (plasma). The ethereal extracts were dried and derivatized by incubation at 60 degrees C with methyl iodide in acetone in the pre...
The ultra long-acting β -adrenoceptor agonist olodaterol plus the ultra long-acting muscarinic antagonist tiotropium bromide are known to relax equine airways. In human bronchi combining these drugs elicits a positive interaction, thus we aimed to characterize this information further in equine isolated airways stimulated by electrical field stimulation (EFS) and using the Concentration-Reduction Index (CRI) and Combination Index (CI) equations. The drugs were administered alone and together by reproducing ex vivo the concentration-ratio delivered by the currently available fixed-dose combina...
Serrano L, Lees P.The butyrophenone tranquilliser, azaperone, was administered intramuscularly to ponies in five series of experiments, using a dose level of 0-4 mg/kg once and 0-8 mg/kg four times. An excellent or good sedative effect was usually obtained with both dose levels, but the response was more consistent with the higher dose. The onset of sedation was apparent within 10 min of administration, the maximal effect usually occurring between 20 and 60 min while sedation was no longer apparent after 2 to 6 h. Body temperature was reduced in all animals for at least 2 h and respiratory rate was increased in...
Garcia P, Pinètre J, Morel S, Jaubert M, Deruy X, Perot I, Delcourt V, Loup B, Popot MA, Bailly-Chouriberry L.Bisphosphonates are prohibited drugs according to Article 6 of the International Agreement on Breeding, Racing and Wagering of the International Federation of Horseracing Authorities (IFHA) and the International Equestrian Federation (FEI). These compounds are used for the treatment of lameness, navicular and bone diseases in horses and are divided into two groups: non-nitrogen-containing bisphosphonate drugs (e.g. clodronic acid) and nitrogen-containing bisphosphonate drugs (e.g. zoledronic acid). Their hydrophilic properties and the high affinity for the bone matrix make the control of their...
Burrows GE, MacAllister CG, Beckstrom DA, Nick JT.The plasma concentrations and pharmacokinetics of rifampin disposition were determined after a single IV, IM, or oral dose of 10 mg/kg of body weight and an oral dose of 25 mg/kg. The overall elimination rate constants per minute were similar for the 10 mg/kg dose (0.0021 +/- 0.0004, IV; 0.0017 +/- 0.0002, IM; and 0.0023 +/- 0.0006, orally). The apparent bioavailability was moderate to low for IM and oral administrations (59.8% +/- 3.2% and 39.5% +/- 5.0%, respectively). The rate of absorption was most rapid for oral administration with an absorption half-life of 249.7 +/- 71.6 minutes as comp...
Sams R, Gerken DF, Ashcraft SM.The pharmacokinetics and urinary excretion of ketoprofen in six healthy mares after the first and last of five daily intravenous doses of 2.2 mg of ketoprofen per kg body weight were investigated using a high-performance liquid chromatographic (HPLC) method for determining plasma and urinary ketoprofen concentrations. Plasma ketoprofen concentrations declined triexponentially after each dose with no significant differences in plasma concentrations or pharmacokinetic parameter values between the first and last doses. The harmonic mean of the terminal elimination half-life of ketoprofen after th...
Garcia Lascurain AA, Sumano Lopez H, Steffey EP, Santillán Doherty P, Hernandez EN.To characterize behavioral and physiological responses to short-term, unsupplemented intravenous (IV) anesthesia in healthy horses at high altitude (2240 m), and to test the hypothesis that the dose of butorphanol modifies the response of the horse to propofol anesthesia following xylazine pre-medication. Methods: Randomized prospective butorphanol dose cross-over experimental design. Animals Eight healthy horses, 13 +/- 6 (mean +/- SD) years of age, and weighing 523 +/- 26 kg. Methods: Each horse was anesthetized three times with at least 3 weeks between each anesthesia. After collecting pre-...
Ganeshpurkar A, Singh R, Kumar D, Gutti G, Sardana D, Shivhare S, Singh RB, Kumar A, Singh SK.Machine learning (ML), an emerging field in drug design, has the potential to predict toxicity, shape-based analysis of inhibitors, scoring function (SF) etc. In the present study, a homology model, docking protocol, and a dedicated SF have been developed to identify the inhibitors of horse butyrylcholinesterase (BChE) enzyme. Horse BChE enzyme has homology with human BChE and is a substitute for the screening of inhibitors. The developed homology model was validated and the active site residues were identified from Cavityplus to generate grid box for docking. The validation of docking invol...
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...
Morris DL, Taylor DH, Daniels D, Riley EM, Richards KS.Ovine and equine protoscoleces of Echinococcus granulosus were cultured for 26 days with our without praziquantel and viability assessed, by eosin exclusion, for cultures in various drug concentrations (50, 250 and 500 micrograms/l) and periods of exposure (1, 3 or 7 days (d] before removing/'rescuing' to drug-free medium. Drug efficacy was proportional to drug concentration and to length of exposure. At higher drug concentrations shorter exposures were required to produce the effect of continuous drug treatment, 1d therapy at 500 micrograms/l killing 96% ovine protoscoleces by day 14 whereas ...
Peck KE, Matthews NS, Taylor TS, Mealey KL.To compare serum disposition of sulfamethoxazole and trimethoprim after IV administration to donkeys, mules, and horses. Methods: 5 donkeys, 5 mules, and 3 horses. Methods: Blood samples were collected before (time 0) and 5, 15, 30, and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 24 hours after IV administration of sulfamethoxazole (12.5 mg/kg) and trimethoprim (2.5 mg/kg). Serum was analyzed in triplicate with high-performance liquid chromatography for determination of sulfamethoxazole and trimethoprim concentrations. Serum concentration-time curve for each ani...
Pass MA, Mogg TD.Amitraz and its active metabolite BTS27271 were given intravenously to ponies and sheep at equimolar doses of 1 mg/kg and 0.68 mg/kg, respectively, and the plasma concentrations of amitraz and BTS27271 estimated at various times thereafter. Amitraz was hydrolysed to BTS27271 in both species. Amitraz was undetectable in sheep plasma after approximately 5 min but persisted in the plasma of ponies for at least 90 min. The persistence of unmetabolized amitraz in ponies may have implications for the toxicity of amitraz in that species. The primary and secondary disposition half-lives of amitraz in ...
