Pharmaceuticals in equine medicine encompass a wide range of drugs and therapeutic agents used to treat various conditions in horses. These substances include analgesics, anti-inflammatories, antibiotics, sedatives, and anthelmintics, among others. Each class of pharmaceuticals is designed to address specific health issues, such as pain management, infection control, or parasitic infestations. The pharmacokinetics and pharmacodynamics of these drugs can vary significantly between horses and other species, necessitating careful consideration of dosage and administration methods. This page compiles peer-reviewed research studies and scholarly articles that explore the development, efficacy, safety, and regulatory aspects of pharmaceuticals used in equine healthcare.
Legere RM, Taylor DR, Davis JL, Bello K, Parker C, Judd RL, Wooldridge AA.Chronic insulin dysregulation is challenging to manage with pharmaceuticals in horses. Pioglitazone improves insulin sensitivity in humans, and the pharmacokinetics of pioglitazone have been evaluated in horses. The objectives of this study were to assess the pharmacodynamic effects of oral pioglitazone on morphometric parameters, hepatic enzyme activity and function, adipokines, and enteroinsular response to oral sugar. A prospective pilot study was performed using fifteen adult equids (8 ponies, 7 horses) to evaluate the effects of short-term pioglitazone administration (2 mg/kg PO q 24 hou...
Hertzsch R, Richter A.Based on their performance-enhancing potential, caffeine and theophylline are prohibited substances in equine sports. Residues in horses can be caused by wilful application or by unintended uptake of contaminated feed. The International Federation of Horseracing Authorities recently introduced international residue limits (IRLs) to facilitate the discrimination between pharmacological relevant and irrelevant concentrations in doping samples. The objective of this study was to investigate the scientific validity of these IRLs. A systematic analysis was performed to assess the IRLs by different ...
Gajardo G, López-Muñoz R, Plaza A, Uberti B, Sarmiento J, Morán G, Henríquez C.Tamoxifen (TAM), a selective modulator of estrogen receptors (SERMs) has been recently explored as a therapeutic option for the oral treatment of airway inflammation in the horse. The objective of this work was to establish pharmacokinetic parameters of TAM and its main metabolites in equines, as well as to determine its clinical safety in short-term treatments. Results: We determined TAM and its three main metabolites (4-OH tamoxifen, endoxifen, and N-desmethyl tamoxifen) in plasma after single administration of 0.25 mg/kg in healthy adult horses ( = 12). A maximum concentration of TAM w...
Berryhill EH, Knych H, Edman JM, Magdesian KG.The neurokinin-1 (NK) receptor antagonist, maropitant citrate, mitigates nausea and vomiting in dogs and cats. Nausea is poorly understood and likely under-recognized in horses. Use of NK-1 receptor antagonists in horses has not been reported. The purpose of this study was to determine the pharmacokinetic profile of maropitant in seven adult horses after single intravenous (IV; 1 mg/kg) and intragastric (IG; 2 mg/kg) doses. A randomized, crossover design was performed. Serial blood samples were collected after dosing; maropitant concentrations were measured using LC-MS/MS. Pharmacokinetic pa...
Stojiljkovic N, Leroux F, Bubanj S, Popot MA, Paris A, Tabet JC, Junot C.There is an urgent need to implement holistic and untargeted doping control protocols with improved discriminatory power, compared to conventional methods that only target doping agents. Metabolomics, which aims to characterize all metabolites present in biological matrices, could fulfill this need. In this context, the aim of this study was to evaluate the impact of environmental factors on the ability to obtain a metabolic signature of stanozolol administration in horse doping situation. Urine samples from 16 horses breeded in two different places were collected over a one-year period, befor...
Mercer MA, McKenzie HC, Davis JL, Wilson KE, Hodgson DR, Cecere TE, McIntosh BJ.There are no published studies on the pharmacokinetics of acetaminophen at the dosage used clinically (20 mg/kg), nor has the safety of multiple doses in horses been investigated. Objective: Define the pharmacokinetic parameters of oral acetaminophen at 20 mg/kg in adult horses as a single dose, and twice daily for 14 days to assess the safety of multiple dosing. Methods: Pharmacokinetic study, multiple dose safety study. Methods: Eight healthy Thoroughbred geldings were given acetaminophen (20 mg/kg; 500 mg tablets) orally as a single dose followed by doses every 12 h for 14 days. Seri...
Genangeli M, Caprioli G, Cortese M, Laus F, Petrelli R, Ricciutelli M, Sagratini G, Sartori S, Vittori S.A new fast and easy analytical procedure for the simultaneous detection and quantification of 9 anabolic steroids (deslorelin, dexamethasone sodium phosphate, prednisolone, methylprednisolone, stanozolol, boldenone, nandrolone, dexamethasone isonicotinate and altrenogest) in horse urine for doping control have been developed by using the ultra-high-performance liquid chromatography coupled with tandem mass spectrometry technique (UHPLC-MS/MS). A total amount of 400 μl of sample was evaporated, restored and injected in the UHPLC-MS/MS. The proposed method was fully validated showing a recove...
Rangel-Nava A, Ramírez-Uribe JM, Recillas-Morales S, Ibancovichi-Camarillo JA, Venebra-Muñoz A, Sánchez-Aparicio P.The objective of the study was to conduct a review of the pharmacological regulation and pharmacokinetic parameters of firocoxib when administered orally or intravenously in horses. A search for literature was done in SCOPUS and PubMed for studies that had to evaluate the pharmacological regulation as well as the pharmacokinetic parameters of firocoxib when administered in horses. The nonsteroidal anti-inflammatory drugs have analgesic, anti-inflammatory, antipyretics, and antiendotoxic effects. The newly developed is selective to COX2 characterized by less adverse effects in veterinary patien...
Di Salvo A, Chiaradia E, Della Rocca G, Giorgi M, Mancini F, Marenzoni ML, Conti MB, Nannarone S.Intra-articular administration of analgesics is performed to ensure good perioperative pain management avoiding undesirable systemic effects. To evaluate the effect of intra-articular injection of tramadol on postoperative pain after arthroscopy in horses and to determine whether tramadol had a local effect. Before the in vivo study, an in vitro test was performed aiming to evaluate the viability of equine chondrocytes after exposure to various concentrations of tramadol. The concentration identified as most appropriate was used to treat the horses' joints. Twelve horses affected by osteochond...
Mendoza FJ, Serrano-Rodriguez JM, Perez-Ecija A.Nonsteroidal anti-inflammatory drugs are administered in horses for several systemic diseases. Selective cyclooxygenase-2 inhibitors are preferred because of lower risk of adverse effects. Several meloxicam formulations have been tested in horses, but a recently marketed granule oral formulation has not been studied. Objective: To characterize the pharmacokinetics of a novel granule meloxicam formulation in fasted and fed horses, and to compare pharmacokinetic features with oral suspension and tablets. Methods: Seven healthy adult horses. Methods: Meloxicam was administered at 0.6 mg/kg in fas...
Kim Y, Seo C, Oh S, Kwak J, Jung S, Sin E, Kim H, Ji M, Lee HS, Park HJ, Lee G, Yu J, Kim M, Lee W, Paik MJ.The authors have retracted this article [1] because after publication they became aware that the equine urine samples analysed for loxoprofen in this study were in fact equine plasma samples. Therefore the results and conclusions of this article cannot be relied upon. All authors agree to this retraction.
Müntener C, Kupper J, Naegeli H, Gassner B.A total of 306 reports of adverse reactions to veterinary medicinal products were received during the year 2017 representing an increase of 21% compared to the previous year. The majority of these reports described reactions concerning companion animals (180 dogs and 59 cats) as well as cattle (38 reports) and horses (14 reports). Most of the reported reactions were linked to the use of antiparasitics (158 reports), hormone products (30 reports) and anti-inflammatory products (25 reports). 40 reports were generated from consultations with Tox Info Suisse in Zürich and mainly involved the ex...
Rudolph W, Remane D, Wissenbach DK, Peters FT.1. Ergopeptine alkaloids like ergovaline and ergotamine are suspected to be associated with fescue toxicosis and ergotism in horses. Information on the metabolism of ergot alkaloids is scarce, especially in horses, but needed for toxicological analysis of these drugs in urine/feces of affected horses. The aim of this study was to investigate the metabolism of ergovaline, ergotamine, ergocristine, and ergocryptine in horses and comparison to humans. 2. Supernatants of alkaloid incubations with equine and human liver S9 fractions were analyzed by reversed-phase liquid-chromatography coupled to h...
Kusano K, Minamijima Y, Mashita S, Kunii H, Yamashita S, Nagata S.Repeated topical application of indomethacin is common in Japanese racehorses, despite the lack of pharmacokinetic data. Objective: To determine the concentrations of indomethacin and its metabolite, desmethylindomethacin, in plasma and urine of Thoroughbreds topically treated repeatedly with indomethacin. Methods: In vivo experimental. Methods: Seven female Thoroughbreds were topically treated with 50 g of 1% indomethacin cream per horse to the back and hips (500 mg of indomethacin/head/2400 cm , 0.21 g/cm ) for 3 consecutive days. Samples were pretreated by protein precipitation for plas...
You Y, Proctor RM, Vasilko ED, Robinson MA.JWH-250 is a synthetic cannabinoid. Its use is prohibited in equine sport according to the Association of Racing Commissioners International (ARCI) and the Fédération Équestre Internationale (FEI). A doping control method to confirm the presence of four JWH-250 metabolites (JWH-250 4-OH-pentyl, JWH-250 5-OH-pentyl, JWH-250 5-OH-indole, and JWH-250 N-pentanoic acid) in equine urine was developed and validated. Urine samples were treated with acetonitrile and evaporated to concentrate the analytes prior to the analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The chromat...
Stanley S, Van den Berg K, Foo HC, Deng D.The metabolism of the masking agent tolcapone in the horse has been investigated. This substance was found to have undergone various chemical transformations that produced a large variety of phase I metabolites, as well as glucuronide and sulfate conjugation. Confirmation of the presence of tolcapone and the 3-O-methylated metabolite in the blood samples collected up to 240 minutes and in urine obtained up to 24 hours, was successfully conducted using both gas chromatography- and liquid chromatography-tandem mass spectrometry techniques. The 3-O-methyl tolcapone is the better marker to use i...
Martin F, Höglund J, Bergström TF, Karlsson Lindsjö O, Tydén E.The aims of this study were to determine the species of Parascaris present in foals in Sweden and to establish whether anthelmintic resistance to pyrantel and fenbendazole is present on Swedish stud farms. Ascarid eggs collected from different regions in Sweden were karyotyped and were all identified as Parascaris univalens, characterized by one chromosomal pair. Faecal egg count reduction tests were performed on a total of 142 foals on 9 farms between September 2016 and May 2017. Healthy foals with at least 150 eggs per gram faeces (EPG) were included in the study and treated with oral pastes...
You Y, Guan F, D'Ippolito R, Li X, Soma LR, Robinson MA.A hydrophilic interaction liquid chromatography-tandem mass spectrometry method (HILIC-MS/MS) was developed for the simultaneous determination of 28 amphetamine-type stimulants (ATSs) in equine plasma for doping control analysis. In this method, stimulants were recovered from equine plasma by liquid-liquid extraction (LLE) at pH 9.5 using methyl tert-butyl ether and detected on a Thermo Finnigan triple quadrupole mass spectrometer operating in positive-ion mode electrospray ionization. All stimulants were eluted within 7 minutes and baseline separation was achieved for isomeric and isobaric ...
Tozaki T, Karasawa K, Minamijima Y, Ishii H, Kikuchi M, Kakoi H, Hirota KI, Kusano K, Nagata SI.Clinical research on gene therapy has advanced the field of veterinary medicine, and gene doping, which is the illegal use of gene therapy, has become a major concern in horseracing. Since the International Federation of Horseracing Authorities defined the administration of oligonucleotides and its analogues as a genetic therapy in 2017, the development of therapeutic nucleotide-detection techniques has become an urgent need. Most currently marketed and developed oligonucleotide therapeutics for humans consist of modified nucleotides to increase stability, and phosphorothioate (PS) modificatio...
Düsterdieck-Zellmer KF.Systemic administration of tiludronate or clodronate decreases lameness in some horses suffering from navicular syndrome within 2-6 months of treatment. In horses that fail to respond to the first treatment, a follow-up treatment may still improve the lameness. Horses with a lameness duration of less than 6 months have better odds of experiencing improvement in lameness. Bisphosphonate (BP) treatment can result in renal damage, and it is recommended to assess renal function prior to and after treatment. Horses with pre-existing renal compromise should not be treated with BP, as this may promot...
Lee W, Ko BJ, Sim YE, Suh S, Yoon D, Kim S.Urine was most commonly used biological sample in drug test. To create a false-negative test result, some drug abusers were reported to submit animal urine instead of their own. So, the purpose of this study was to compare and differentiate human from animal urine (Rat 370, Pig 12, Horse 10, Cat 8, Dog 13, Cow 10, Monkey 10) samples through the uses of quantitative 1H-NMR and to find biomarkers that can be used for the discrimination of human urine from animal urine. The 1H-NMR spectroscopy was employed and metabolomic analysis with multivariate statistics was carried out. Human urine samples ...
Waraksa E, Woźniak MK, Kłodzińska E, Wrzesień R, Bobrowska-Korczak B, Namieśnik J.Ibuprofen is widely used in human and veterinary medicine for the treatment of chronic pain as well as rheumatic and musculoskeletal disorders. However, the analgesic and anti-inflammatory properties of Ibuprofen have contributed to frequent drug abuse in equestrian sports. A sensitive and rapid gas chromatography with tandem mass spectrometry based method with a simple liquid-liquid extraction and derivatization requiring 200 μL volume of sample and 2 mL of extraction solvent for the simultaneous determination of ibuprofen and its metabolites was developed. The proposed procedure was optim...
Duz M, Marshall JF, Parkin TD.There is little knowledge of the prescription of nonsteroidal anti-inflammatory drugs (NSAIDs) and whether their prescription varies between countries. Objective: To describe prescription practices of NSAIDs in equids in the United Kingdom (UK), United States of America (USA) and Canada. Methods: Descriptive observational study. Methods: Free-text electronic medical records from 141,543 equids from 10 equine practices in the UK, 255,777 equids from 7 equine practices with 20 branches from the USA and 2 practices with 7 branches from Canada were evaluated. A validated text-mining technique was ...
Wang J, Xue J, Kong J, Li J, Zhang S, Cao X.The pharmacokinetic properties of vitacoxib have not been established completely; current dosage recommendations are based on clinical experiences. The primary objective of this study was to describe plasma concentrations and characterize the pharmacokinetics of vitacoxib formulation following oral administrations in horses. Also, the effect of the state of stomach contents on the absorption of vitacoxib was investigated in fed/fasted horses. Blood samples were collected prior to and at various times up to 72 hr post-administration. Drug concentrations were measured using ultra high-performan...
Crotch-Harvey L, Thomas LA, Worgan HJ, Douglas JL, Gilby DE, McEwan NR.Anthelmintics are used as anti-worming agents. Although known to affect their target organisms, nothing has been published regarding their effect on other digestive tract organisms or on metabolites produced by them. The current work investigated effects of fenbendazole, a benzimidazole anthelmintic, on bacteria and ciliates in the equine digestive tract and on and their major metabolites. Animals receiving anthelmintic treatment had high faecal egg counts relative to controls. Analysis was performed over two weeks, with temporal differences detected in bacterial populations but with no other ...
Wong JKY, Choi TLS, Kwok KY, Lei ENY, Wan TSM.Equine hair is becoming an increasingly popular biological matrix for doping control of horse sports; one of the reasons for this is the significantly longer detection window hair can offer. Hair analysis opens up the opportunity for longitudinal monitoring of drug exposure which would otherwise not be possible with the more traditional and common biological matrices, such as urine and blood. As such, there is a need for more multi-target screening methods covering a broad range of prohibited substances in equine hair at the required sensitivities for equine doping control. This paper describe...
Wenzel R, Major D, Hesp K, Doble P.Regulating authorities in the racing industry have restricted the administration of potentially performance enhancing cobalt salts to horses. There are severe penalties for trainers presenting horses with elevated urine cobalt concentrations, and compliance is ensured via analysis of total urinary cobalt at thresholds of 100 μg/L. When cobalt is present as part of the cobalamin molecule it is not considered performance enhancing. This paper demonstrates that a horse can excrete a significant proportion of a commercially available vitamin B12 injection in urine without metabolic modification...
Emmerich IU.In 2017, no new active pharmaceutical ingredients were released on the German market for horses or food-producing animals. Four established veterinary active pharmaceutical ingredients became available for additional species: the ectoparasitic Fluralaner (Exzolt®) of the isoxazoline group was additionally authorized for chickens, the macrolide antibiotics Gamithromycin (Zactran®) and Tulathromycin (Draxxin®) for sheep and the nonsteroidal anti-inflammatory drug Tolfenamic Acid (Tolfedol®) from the fenamate group for cattle and pigs. Additionally, one drug with a new combination of active i...
Tevell A, Bondesson U, Törneke K, Hedeland M.The metabolism of clemastine was studied in dogs, horses, and humans after a single dose of Tavegyl. The urine collected was extracted by solid-phase extraction or hydrolyzed with beta-glucuronidase and then extracted by liquid-liquid extraction, prior to analysis for unchanged drug and phase I and II metabolites by liquid chromatography/tandem mass spectrometry. The metabolites were identified by their molecular mass and interpretation of the product ion spectra, since no standard substances were available. Unchanged drug was recovered in urine samples from dogs and humans, but not from horse...
Dunnett M, Lees P.Analysis of human hair for drug residues is being used increasingly as a diagnostic tool in the investigation of drug use and abuse. Hair analysis is complementary to urine/blood testing in that it can provide an extensive historical record of drug use, is noninvasive, impersonal and can facilitate retesting. However, the technique has not been studied in horses. Objective: That the systemic administration of drugs in horses could be identified by the detection of drug residues in hair. Objective: To evaluate hair analysis as a potential retrospective diagnostic test for drug administration in...
Broberg MN, Knych H, Bondesson U, Pettersson C, Stanley S, Thevis M, Hedeland M.Selective Androgen Receptor Modulators (SARMs) have anabolic properties but less adverse effects than anabolic androgenic steroids. They are prohibited in both equine and human sports and there have been several cases of SARMs findings reported over the last few years. The aim of this study was to investigate the metabolite profile of the SARM ACP-105 (2-chloro-4-[(3-endo)-3-hydroxy-3-methyl-8-azabicyclo[3.2.1]oct-8-yl]-3-methylbenzonitrile) in order to find analytical targets for doping control. Oral administration of ACP-105 was performed in horses, where blood and urine samples were collect...
Hunyadi L, Papich MG, Pusterla N.The purpose of this study was to determine the pharmacokinetics of the FDA-approved labeled dose of diclazuril and compare it to a low dose in plasma and CSF in adult horses. During each research period, six healthy adult horses received 0.5 mg/kg of 1.56% diclazuril pellets (Protazil(TM) , Merck Animal Health) compared to the approved labeled dose of 1 mg/kg orally once in two separate phases. A dose of 0.5 mg/kg was calculated to each horse's weight. Blood was then collected immediately before diclazuril administration and then at regular intervals up to a 168 h. After the last blood collect...
Pippi NL, Lumb WV.An equine model, subjected to three kinds of pain (superficial, deep, and visceral) was used to test effects of analgesic drugs. Two groups of ponies were used. In the first group of six ponies, six drugs (fentanyl, meperidine, methadone, oxymorphone, pentazocine, and xylazine) were given according to a Latin square experimental design, and tests were made at 30-minute intervals for 4 hours. Mean values (control) for the three kinds of pain were obtained before and after the tests and were compared with the mean values (drugs) obtained over 2- and 4-hour intervals (four and eight measurements ...
Barton AK, Heinemann H, Schenk I, Machnik M, Gehlen H.OBJECTIVE To evaluate the influence of respiratory tract disease (ie, recurrent airway obstruction [RAO]) and mode of inhalation on detectability of inhaled budesonide in equine plasma and urine samples. ANIMALS 16 horses (8 healthy control horses and 8 horses affected by RAO, as determined by results of clinical examination, blood gas analysis, bronchoscopy, and cytologic examination of bronchoalveolar lavage fluid). PROCEDURES 4 horses of each group inhaled budesonide (3 μg/kg) twice daily for 10 days while at rest, and the remaining 4 horses of each group inhaled budesonide during lunging ...
Slocombe JO, McCraw BM.Trials were conducted in ponies to evaluate the efficacy of pyrantel pamoate (Strongid-T(R)) and two newer anthelmintics not yet commercially available, nitramisole and avermectin B(1)a, against migrating Strongylus vulgaris larvae. Ponies were removed from their mares within 24-48 hr after birth and reared in isolation, worm free. Between six and 14 weeks of age they were infected with 2000 or 2500 infective S. vulgaris larvae. Subsequently, they were monitored daily for clinical signs until the experiment terminated at 28 days postinfection. All ponies showed increased body temperature and r...
Tobin T, Dirikolu L, Brewer K, Hughes CG.Equine forensic science can now detect concentrations down to 25 femtograms/mL (parts per quadrillion, ppq) or less in blood and urine. As such, horsemen are increasingly at risk of inadvertent 'positives' due to therapeutic medication 'overages' or trace identifications of dietary or environmental substances. Reviewed here are the factors which determine detection times and 'withdrawal times' for substances administered to horses. Withdrawal times are affected by many factors, including dose, formulation, route and frequency of administration, bioavailability, plasma half-life, sensitivity of...
Gokbulut C, Cirak VY, Senlik B, Yildirim F, McKellar QA.This study aimed to determine the plasma disposition and faecal excretion of netobimin (NTB) and its respective metabolites as well as the efficacy against strongyles in horses following oral administration. Netobimin (10mg/kg) was administered orally to 8 horses. Blood and faecal samples were collected from 1 to 120h post-treatment and analysed by high performance liquid chromatography (HPLC). Using a chiral phase-based HPLC, plasma disposition of ABZSO enantiomers produced was also determined. Faecal strongyle egg counts (EPG) were performed by a modified McMaster's technique before and afte...
Jaussaud P, Guieu D, Bellon C, Barbier B, Lhopital MC, Sechet R, Courtot D, Toutain PL.The pharmacokinetics of tolfenamic acid were studied in five ponies after an intravenous (iv) administration (2 mg/kg bodyweight [bwt]) and in four horses after an oral administration (30 mg/kg bwt) of tolfenamic acid. The plasma levels were determined by high pressure liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). For the iv administration, a three-compartment model was used to represent the plasma concentration-time curve of the drug. The elimination half-life of the compound was 6.1 +/- 1.5 h, the total body clearance was 72.4 +/- 16.7 ml/kg bwt/h and the ste...
Joré C, Loup B, Garcia P, Paris AC, Popot MA, Audran M, Bonnaire Y, Varlet-Marie E, Bailly-Chouriberry L.Erythropoiesis Stimulating Agents (ESAs) were developed for therapeutic purposes to stimulate red blood cell (RBC) production. Consequently, tissue oxygenation is enhanced as athlete's endurance and ESAs misuse now benefits doping. Our hypothesis is that most of ESAs should have similar mechanisms and thus have the same effects on metabolism. Studying the metabolome variations could allow suspecting the use of any ESAs with a single method by targeting their effects. In this objective, a metabolomic study was carried out on 3 thoroughbred horses with a single administration of 4.2μg/kg of Mir...
Kwok WH, Choi TLS, Kwok KY, Chan GHM, Wong JKY, Wan TSM.The high sensitivity of ultra high performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS) allows the identification of many prohibited substances without pre-concentration, leading to the development of simple and fast 'dilute-and-shoot' methods for doping control for human and equine sports. While the detection of polar drugs in plasma and urine is difficult using liquid-liquid or solid-phase extraction as these substances are poorly extracted, the 'dilute-and-shoot' approach is plausible. This paper describes a 'dilute-and-shoot' UHPLC-HRMS screening me...
Meucci V, Minunni M, Vanni M, Sgorbini M, Corazza M, Intorre L.Detection of nonsteroidal anti-inflammatory drugs (NSAIDs) in equine plasma is a significant analytical problem in veterinary anti-doping controls. Results: A new HPLC method coupled to selective extraction with molecularly imprinted polymers was developed for the simultaneous determination in equine plasma of the NSAIDs phenylbutazone, flunixin, oxyphenbutazone, ketoprofen and naproxen. The analytical performances of the method have been evaluated both in standard solutions and equine plasma samples. Recovery: Molecularly imprinted polymers solid-phase extraction for all NSAIDs was >94% with ...
Liska DA, Akucewich LH, Marsella R, Maxwell LK, Barbara JE, Cole CA.To determine serum pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite in horses after administration of a single IV dose and after single and multiple oral doses. Methods: 8 healthy adult horses. Methods: A crossover study design was used with a washout period of 6 days between treatments. Treatments were IV administration of a single dose of pentoxifylline (8.5 mg/kg) and oral administration of generic sustained-release pentoxifylline (10 mg/kg, q 12 h, for 8 days). Blood samples were collected 0, 1, 3, 6, 12, 20, 30, and 45 minutes and 1, 2, 4, 6, 8, and 12 hours after IV a...
Cutler C, Viljanto M, Hincks P, Habershon-Butcher J, Muir T, Biddle S.LGD-4033 is one of a number of selective androgen receptor modulators (SARMs) that are being developed by the pharmaceutical industry to provide the therapeutic benefits of anabolic androgenic steroids, without the less desirable side effects. Though not available therapeutically, SARMs are available for purchase online as supplement products. The potential for performance enhancing effects associated with these products makes them a significant concern with regards to doping control in sports. The purpose of this study was to investigate the metabolism of LGD-4033 in the horse following oral ...
Kwok WH, Leung GN, Wan TS, Curl P, Schiff PJ.Androsta-1,4,6-triene-3,17-dione (ATD) is an irreversible steroidal aromatase inhibitor and is marketed as a supplement. It has been reported to effectively reduce estrogen biosynthesis and significantly increase the levels of endogenous steroids such as dihydrotestosterone and testosterone in human. ATD abuses have been reported in human sports. Its metabolism in human has been studied, and the in vitro metabolic study of ATD in horses has been reported, however, little is known about its biotransformation and elimination in horses. This paper describes the in vitro and in vivo metabolism stu...
Soma LR, Behrend E, Rudy J, Sweeney RW.The disposition of flunixin meglumine administered IV at a dosage of 1.1 mg/kg was described by a 2-compartment model; the alpha and beta half-lives (t1/2) were 0.61 and 1.5 hours, respectively. When administered IV at a rate of 2.2 mg/kg, the disposition was best described by a 3-compartment model, and the alpha, beta, and lambda t1/2 were 0.16, 1.52, and 6.00 hours, respectively. The zero-time plasma concentrations after flunixin meglumine was administered at 1.1 and 2.2 mg/kg were 9.3 +/- 0.76 and 21.5 +/- 7.4 mg/L, respectively. The bioavailability after oral administration of 1.1 mg/kg wa...
Doucet MY, Vrins AA, Dionne R, Alva R, Ericsson G.The efficacy of a paste formulation of the H+, K+, -ATPase inhibitor omeprazole was evaluated in standardbred racehorses for the treatment and prevention of gastric ulcers. Twenty standardbred racehorses in training, aged 2 to 9 years, were enrolled from 2 training centres in this field trial. Endoscopic examinations confirmed the presence of gastric ulcers in all horses, prior to allocation and treatment and on day 0. Lesions were scored on a scale of 0 to 3 (intact epithelium to extensive ulceration). Replicates were formed, based on training level and location. Within replicates, 1 horse wa...
Knych HK, McKemie DS, Stanley SD.The use of performance-enhancing drugs in the horse racing industry combined with the need for more rational approaches in the use of therapeutic agents in equids necessitates additional studies on the spectrum, content, and catalytic activities of hepatic cytochrome P450 monooxygenases in this species. In this study, three cytochrome P450 (P450) monooxygenases in the 3A family were cloned from, sequenced, and expressed in a baculovirus expression system. The proteins were designated CYP3A89, CYP3A96, and CYP3A97. Expression studies produced various results among the three proteins. CYP3A89 ap...
Bermingham E, Davis JL, Whittem T.The goal of this editorial is to discuss best practice design, execution and reporting of a pharmacokinetic (PK) study in horses. Our target readers are clinicians who plan to perform this type of research, in a field, clinic or research setting but we also hope that this article might help readers of such work to appraise the articles and understand the quality of the studies. Our emphasis will be on appropriate study design and analytical method, drug and drug formulation choice and route of administration, animal choice, sample collection, storage and shipping, and reporting, rather than th...
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...
Frederick J, Giguère S, Butterworth K, Pellegrini-Masini A, Casas-Dolz R, Turpin MM.5 aged (≥ 17 years old) horses developed life-threatening Internal hemorrhage following IV administration of phenylephrine at 3 hospitals. Results: All 5 horses developed severe hemothorax, hemoabdomen, or both within minutes to hours following administration of phenylephrine. Results: Four of 5 horses died of hemorrhagic shock, and 1 horse survived with a blood transfusion. The exact source of hemorrhage was Identified In only 1 horse. Medical records of all horses with nephrosplenic entrapment of the large colon and treated with phenylephrine at the University of Florida Veterinary Medical...
De Leo M, Giorgi M, Saccomanni G, Manera C, Braca A.Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat pain in humans. The clinical response of tramadol is strictly correlated to its metabolism, because of the different analgesic activity of its metabolites. O-Desmethyltramadol (M1), its major active metabolite, is 200 times more potent at the micro-receptor than the parent drug. In recent years tramadol has been widely introduced in veterinary medicine but its use has been questioned in some species. The aim of the present study was to develop a new sensible method to detect the whole ...
Szarka S, Prokai L.We report a high-throughput chip-based nanoelectrospray ionization method coupled with Fourier transform mass spectrometry to screen for local anesthetics in samples collected by swabbing. These drugs have been used to mask pain on the limbs of walking horses after forbidden practices of soring or physical abuse. Optimized for lidocaine, the method afforded sub-ppm mass accuracy for nine local anesthetics included in the study. From doped cotton swabs, two third and all of the analytes were detected after adding 10 ng and 100 ng of each drug, respectively. Benzocaine and/or lidocaine were ...
Dyson SJ.It was hypothesised that in solar bone images of the front feet of clinically normal horses, or horses with lameness unrelated to the front feet, there would be less than a 10% difference in the ratio of uptake of radiopharmaceutical in either the region of the navicular bone, or the region of insertion of the deep digital flexor tendon (DDFT), compared to the peripheral regions of the distal phalanx. Nuclear scintigraphic examination of the front feet of 15 Grand Prix show jumping horses, all of which were free from detectable lameness, was performed using dorsal, lateral and solar images. Th...
Larsen SW, Frost AB, Ostergaard J, Thomsen MH, Jacobsen S, Skonberg C, Hansen SH, Jensen HE, Larsen C.The objective of the present study was to explore the potential of using an in situ suspension forming drug delivery system of celecoxib to provide sustained drug exposure in the joint cavity following intra-articular administration. In vitro, precipitates were formed upon addition of a 400 mg/mL solution of celecoxib in polyethylene glycol 400 (PEG 400) to phosphate buffer, pH 7.4, or synovial fluid. The in vitro release profiles of the in situ formed suspensions were characterized by an initial fast release followed by a slower constant flux. In buffer solutions, these fluxes were comparable...
Lee W, Ko BJ, Sim YE, Suh S, Yoon D, Kim S.Urine was most commonly used biological sample in drug test. To create a false-negative test result, some drug abusers were reported to submit animal urine instead of their own. So, the purpose of this study was to compare and differentiate human from animal urine (Rat 370, Pig 12, Horse 10, Cat 8, Dog 13, Cow 10, Monkey 10) samples through the uses of quantitative 1H-NMR and to find biomarkers that can be used for the discrimination of human urine from animal urine. The 1H-NMR spectroscopy was employed and metabolomic analysis with multivariate statistics was carried out. Human urine samples ...
