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Topic:Drug

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.
The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes.
Scientific reports    March 21, 2016   Volume 6 23121 doi: 10.1038/srep23121
Chindera K, Mahato M, Sharma AK, Horsley H, Kloc-Muniak K, Kamaruzzaman NF, Kumar S, McFarlane A, Stach J, Bentin T, Good L.To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles whe...
Investigation of the selective androgen receptor modulators S1, S4 and S22 and their metabolites in equine plasma using high-resolution mass spectrometry.
Rapid communications in mass spectrometry : RCM    March 13, 2016   Volume 30, Issue 7 833-842 doi: 10.1002/rcm.7512
Hansson A, Knych H, Stanley S, Thevis M, Bondesson U, Hedeland M.Selective androgen receptor modulators (SARMs) are prohibited in sports due to their performance enhancing ability. It is important to investigate the metabolism to determine appropriate targets for doping control. This is the first study where the equine metabolites of SARMs S1, S4 (Andarine) and S22 (Ostarine) have been studied in plasma. Methods: Each SARM was administered to three horses as an intravenous bolus dose and plasma samples were collected. The samples were pretreated with protein precipitation using cold acetonitrile before separation by liquid chromatography. The mass spectrome...
Characterization of equine cytochrome P450: role of CYP3A in the metabolism of diazepam.
Journal of veterinary pharmacology and therapeutics    March 11, 2016   Volume 39, Issue 5 478-487 doi: 10.1111/jvp.12303
Nakayama SM, Ikenaka Y, Hayami A, Mizukawa H, Darwish WS, Watanabe KP, Kawai YK, Ishizuka M.Research on drug metabolism and pharmacokinetics in large animal species including the horse is scarce because of the challenges in conducting in vivo studies. The metabolic reactions catalyzed by cytochrome P450s (CYPs) are central to drug pharmacokinetics. This study elucidated the characteristics of equine CYPs using diazepam (DZP) as a model compound as this drug is widely used as an anesthetic and sedative in horses, and is principally metabolized by CYPs. Diazepam metabolic activities were measured in vitro using horse and rat liver microsomes to clarify the species differences in enzy...
Anthelmintics efficacy against intestinal strongyles in horses of Sardinia, Italy.
Parasite epidemiology and control    March 8, 2016   Volume 1, Issue 2 15-19 doi: 10.1016/j.parepi.2016.01.001
Sanna G, Pipia AP, Tamponi C, Manca R, Varcasia A, Traversa D, Scala A.Intestinal strongyles (IS) are the most important parasites of equids, due to their high prevalence worldwide, pathogenicity and the spread of drug-resistant populations. Despite the large number of horses bred in Sardinia Island, Italy, no data are available on the efficacy of anthelmintic compounds in the control of horse strongylosis. Therefore the aim of the present study was to evaluate the efficacy of five commercial anthelmintic formulations containing fenbendazole (FBZ), pyrantel (PYR), moxidectin (MOX) and two ivermectin formulations (IVM1 and IVM2) against IS in Sardinia by performin...
Pharmacokinetics of methocarbamol and phenylbutazone in exercised Thoroughbred horses.
Journal of veterinary pharmacology and therapeutics    February 29, 2016   Volume 39, Issue 5 469-477 doi: 10.1111/jvp.12298
Knych HK, Stanley SD, Seminoff KN, McKemie DS, Kass PH.Methocarbamol (MCBL) is commonly used in performance horses for the treatment of skeletal muscle disorders. Current regulatory recommendations for show horses and racehorses are based on a single oral dose of 5 g, although doses in excess of this are often administered. The goal of the current study was to characterize the disposition of MCBL following higher dose administration and administration in combination with another commonly used drug in performance horses, phenylbutazone (PBZ). Exercised Thoroughbred horses were administered various doses of MCBL as a sole agent and MCBL in combinat...
Clinical effects and pharmacokinetic variables of romifidine and the peripheral α2 -adrenoceptor antagonist MK-467 in horses.
Veterinary anaesthesia and analgesia    February 26, 2016   Volume 43, Issue 6 599-610 doi: 10.1111/vaa.12354
de Vries A, Pakkanen SA, Raekallio MR, Ekiri A, Scheinin M, Taylor PM, Vainio OM.To investigate the effects of MK-467 on sedation quality, and cardiopulmonary and pharmacokinetic variables in horses sedated intravenously (IV) with romifidine. Methods: Experimental, randomized, crossover design. Methods: Seven healthy mares. Methods: Romifidine (80 μg kg-1 ; R) and MK-467 (200 μg kg-1 ; MK) were administered IV alone and in combination (R + MK). Levels of sedation and borborygmi were scored. Heart rate (HR), direct arterial blood pressure (ABP) and respiratory rate (fR ) were recorded. Arterial and venous blood gas analyses were performed and venous plasma drug conc...
Crystal structure of equine serum albumin in complex with cetirizine reveals a novel drug binding site.
Molecular immunology    February 17, 2016   Volume 71 143-151 doi: 10.1016/j.molimm.2016.02.003
Handing KB, Shabalin IG, Szlachta K, Majorek KA, Minor W.Serum albumin (SA) is the main transporter of drugs in mammalian blood plasma. Here, we report the first crystal structure of equine serum albumin (ESA) in complex with antihistamine drug cetirizine at a resolution of 2.1Å. Cetirizine is bound in two sites--a novel drug binding site (CBS1) and the fatty acid binding site 6 (CBS2). Both sites differ from those that have been proposed in multiple reports based on equilibrium dialysis and fluorescence studies for mammalian albumins as cetirizine binding sites. We show that the residues forming the binding pockets in ESA are highly conserved in h...
Differential expression of β-tubulin isotypes in different life stages of Parascaris spp after exposure to thiabendazole.
Molecular and biochemical parasitology    February 12, 2016   Volume 205, Issue 1-2 22-28 doi: 10.1016/j.molbiopara.2016.02.004
Tydén E, Skarin M, Andersson-Franko M, Sjöblom M, Höglund J.Anthelmintic resistance (AR) to macrocyclic lactones (ML) has been described in Parascaris of horses world-wide. In contrast, benzimidazoles (BZ) are still effective, although reduced efficacy to this drug class was recently reported. The mode of action of BZ is binding to β-tubulin, which prevents polymerisation of microtubules. In this study, β-tubulin gene expression of isotypes 1 and 2 was investigated at seven time points (0, 6, 24, 72, 96 and 120 h) during embryogenesis and in adult worms. In addition, an in ovo larval developmental test was developed to study β-tubulin gene expressio...
Pharmacokinetics and Pulmonary Distribution of Clarithromycin and Rifampicin after Concomitant and Consecutive Administration in Foals.
Molecular pharmaceutics    February 11, 2016   Volume 13, Issue 3 1089-1099 doi: 10.1021/acs.molpharmaceut.5b00907
Berlin S, Spieckermann L, Oswald S, Keiser M, Lumpe S, Ullrich A, Grube M, Hasan M, Venner M, Siegmund W.Drug interactions often result from multiple pharmacokinetic changes, such as after rifampicin (RIF) and clarithromycin (CLA) in the treatment of abscessing lung diseases. Comedication of RIF may interact with CLA disposition by either induction of presystemic elimination processes and/or inhibition of uptake mechanisms because it regulates gene transcription and modulates function of various CYP enzymes, multidrug efflux and uptake transporters for which CLA is a substrate. To distinguish the transcriptional changes from the modulating interaction components upon CLA absorption and pulmonary ...
Label-free proteomic analysis of the hydrophobic membrane protein complement in articular chondrocytes: a technique for identification of membrane biomarkers.
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals    February 10, 2016   Volume 20, Issue 8 572-589 doi: 10.3109/1354750X.2015.1130191
Matta C, Zhang X, Liddell S, Smith JR, Mobasheri A.There is insufficient knowledge about the chondrocyte membranome and its molecular composition. Objective: To develop a Triton X-114 based separation technique using nanoLC-MS/MS combined with shotgun proteomics to identify chondrocyte membrane proteins. Methods: Articular chondrocytes from equine metacarpophalangeal joints were separated into hydrophobic and hydrophilic fractions; trypsin-digested proteins were analysed by nanoLC-MS/MS. Results: A total of 315 proteins were identified. The phase extraction method yielded a high proportion of membrane proteins (56%) including CD276, S100-A6 an...
Quantification of horse plasma proteins altered by xylazine using the fluorogenic derivatization-liquid chromatography-tandem mass spectrometry.
Journal of equine science    February 3, 2016   Volume 26, Issue 4 141-146 doi: 10.1294/jes.26.141
Mori M, Ichibangase T, Yamashita S, Kijima-Suda I, Kawahara M, Imai K.In the doping tests currently used in horse racing, prohibited substances or their metabolites are usually directly detected in urine or blood samples. However, despite their lasting pharmaceutical effects, some prohibited substances are rapidly eliminated from horse urine and blood, making them difficult to detect. Therefore, new indirect biomarkers for doping, such as plasma proteins that are increased by the prohibited substances, have recently attracted much attention. Here, a fluorogenic derivatization-liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS) method was adopted for hor...
Commentary on Paper: “Controlling the misuse of cobalt in horses”.
Drug testing and analysis    January 15, 2016   Volume 8, Issue 8 880-881 doi: 10.1002/dta.1901
Major D, Wenzel R.No abstract available
Pharmacokinetics of guaifenesin following administration of multiple doses to exercised Thoroughbred horses.
Journal of veterinary pharmacology and therapeutics    January 14, 2016   Volume 39, Issue 4 416-419 doi: 10.1111/jvp.12287
Knych HK, Stanley SD, Benson D, Arthur RM.Guaifenesin is an expectorant commonly used in performance horses to aid in the clearance of mucus from the airways. Guaifenesin is also a centrally acting skeletal muscle relaxant and as such is a prohibited drug with withdrawal necessary prior to competition. To the authors' knowledge, there are no reports in the literature describing single or multiple oral administrations of guaifenesin in the horse to determine a regulatory threshold and related withdrawal time. Therefore, the objective of the current study was to describe the pharmacokinetics of guaifenesin following oral administration ...
Cytokine, catabolic enzyme and structural matrix gene expression in synovial fluid following intra-articular administration of triamcinolone acetonide in exercised horses.
Equine veterinary journal    January 8, 2016   Volume 49, Issue 1 107-115 doi: 10.1111/evj.12531
Knych HK, Vidal MA, Chouicha N, Mitchell M, Kass PH.The frequent use of intra-articular triamcinolone acetonide (TA) in performance horses warrants further study of the duration of as well as the beneficial and detrimental effects on gene expression associated with administration. Objective: To assess the effects of intra-articular administration of TA on the expression of selected anti- and proinflammatory and structural matrix genes following its administration into joints of exercised Thoroughbred horses and to correlate these effects with plasma and synovial fluid drug concentrations. Methods: Block design experiment. Methods: Eight exercis...
Plasma disposition, milk excretion and parasitological efficacy of mebendazole in donkeys naturally infected by Cyathostominae.
Veterinary parasitology    January 2, 2016   Volume 217 95-100 doi: 10.1016/j.vetpar.2015.12.031
Gokbulut C, Aksit D, Santoro M, Roncoroni C, Mariani U, Buono F, Rufrano D, Fagiolo A, Veneziano V.Mebendazole (MBZ) has been licensed for use in horses and donkeys, however there are no data available in the literature regarding its pharmacokinetic disposition and efficacy in donkeys. This study was designed to determine the plasma disposition, milk excretion and anthelmintic efficacy of MBZ in donkeys naturally infected by Cyathostominae. The animals were allocated to three groups, each of six donkeys. One group was untreated control (C-group) and the others were treated using a paste formulation of MBZ administered per os at the manufacturer's recommended horse dosage of 10 mg/kg body we...
Qualitative and Quantitative Characteristics of the Electroencephalogram in Normal Horses during Administration of Inhaled Anesthesia.
Journal of veterinary internal medicine    December 30, 2015   Volume 30, Issue 1 289-303 doi: 10.1111/jvim.13813
Williams DC, Brosnan RJ, Fletcher DJ, Aleman M, Holliday TA, Tharp B, Kass PH, LeCouteur RA, Steffey EP.The effects of anesthesia on the equine electroencephalogram (EEG) after administration of various drugs for sedation, induction, and maintenance are known, but not that the effect of inhaled anesthetics alone for EEG recording. Objective: To determine the effects of isoflurane and halothane, administered as single agents at multiple levels, on the EEG and quantitative EEG (qEEG) of normal horses. Methods: Six healthy horses. Methods: Prospective study. Digital EEG with video and quantitative EEG (qEEG) were recorded after the administration of one of the 2 anesthetics, isoflurane or halothane...
In vitro growth inhibitory efficacy of some target specific novel drug molecules against Theileria equi.
Veterinary parasitology    December 29, 2015   Volume 217 1-6 doi: 10.1016/j.vetpar.2015.12.024
Gopalakrishnan A, Maji C, Dahiya RK, Suthar A, Kumar R, Gupta AK, Dimri U, Kumar S.The in vitro growth inhibitory efficacies of five drug molecules against Theileria equi were evaluated in in vitro cultured parasites. A continuous microaerophilic stationary-phase culture (MASP) system was established for propagation of T. equi parasites. This in vitro culture system was used to assess the growth inhibitory effect of harmaline hydrochloride dihydrate (HHD), hexadecyltrimethylammonium bromide (HDTAB), hesparidin methyl chalcone (HMC), andrographolide and imidocarb dipropionate against T. equi. The 50% inhibitory concentration value of HHD, HDTAB, HMC, and imidocarb dipropionat...
Targeted Metabolomics Approach To Detect the Misuse of Steroidal Aromatase Inhibitors in Equine Sports by Biomarker Profiling.
Analytical chemistry    December 15, 2015   Volume 88, Issue 1 764-772 doi: 10.1021/acs.analchem.5b03165
Chan GH, Ho EN, Leung DK, Wong KS, Wan TS.The use of anabolic androgenic steroids (AAS) is prohibited in both human and equine sports. The conventional approach in doping control testing for AAS (as well as other prohibited substances) is accomplished by the direct detection of target AAS or their characteristic metabolites in biological samples using hyphenated techniques such as gas chromatography or liquid chromatography coupled with mass spectrometry. Such an approach, however, falls short when dealing with unknown designer steroids where reference materials and their pharmacokinetics are not available. In addition, AASs with fast...
Anesthesia of the Equine Neonate in Health and Disease.
The Veterinary clinics of North America. Equine practice    November 28, 2015   Volume 31, Issue 3 567-585 doi: 10.1016/j.cveq.2015.09.002
Fischer B, Clark-Price S.Anesthetizing the neonatal foal presents significant challenges as a result of physiologic differences from the adult equine. This article gives the reader an overview of these differences and the impact they have on anesthetic drug selection, monitoring, and support of the equine neonate. Special emphasis is directed to the sick neonate and appropriate preparation and maintenance of anesthesia in the face of commonly presented disease conditions.
Pharmacokinetics of procaterol in thoroughbred horses.
Journal of veterinary pharmacology and therapeutics    November 5, 2015   Volume 39, Issue 3 264-270 doi: 10.1111/jvp.12272
Kusano K, Nomura M, Toju K, Ishikawa Y, Minamijima Y, Yamashita S, Nagata S.Procaterol (PCR) is a beta-2-adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 μg/kg) and oral (2.0 μg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography-mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady-state volume of the distribution was 1.21 ± 0.23 L/kg, ...
Antimicrobial use and antimicrobial resistance in horses.
Equine veterinary journal    October 18, 2015   Volume 47, Issue 6 747-749 doi: 10.1111/evj.12469
Weese JS.No abstract available
Detection of the selective androgen receptor modulator andarine (S-4) in a routine equine blood doping control sample.
Drug testing and analysis    October 12, 2015   Volume 8, Issue 2 257-261 doi: 10.1002/dta.1867
Cawley AT, Smart C, Greer C, Liu Lau M, Keledjian J.No abstract available
Rhabdomyolysis Secondary to Clenbuterol Use and Exercise.
The Journal of emergency medicine    October 9, 2015   Volume 50, Issue 2 e71-e74 doi: 10.1016/j.jemermed.2015.09.006
Grimmer NM, Gimbar RP, Bursua A, Patel M.The literature regarding rhabdomyolysis secondary to illicit drug use is sparse. Clenbuterol is a bronchodilator approved for veterinary use, which in high doses can increase protein deposition and lipolysis similarly to anabolic steroids, and is thereby abused for bodybuilding and weight loss effects. Clenbuterol has previously been described in case reports to be cardiotoxic, with patient presentations similar to overdoses of sympathomimetic substances, but reports of rhabdomyolysis are limited to a single case series in horses. Methods: We report the first case of rhabdomyolysis secondary t...
Pharmacokinetics of ketorolac tromethamine in horses after intravenous, intramuscular, and oral single-dose administration.
Journal of veterinary pharmacology and therapeutics    September 28, 2015   Volume 39, Issue 2 167-175 doi: 10.1111/jvp.12260
Bianco AW, Constable PD, Cooper BR, Taylor SD.Nonsteroidal anti-inflammatory drugs (NSAIDs) are an integral component of equine analgesia, yet currently available NSAIDs are both limited in their analgesic efficacy and have adverse effects. The NSAID ketorolac tromethamine (KT) is widely used in humans as a potent morphine-sparing analgesic drug but has not been fully evaluated in horses. The purpose of this study was to determine the pharmacokinetic profile of KT in horses after intravenous (i.v.), intramuscular (i.m.), and oral (p.o.) administration. Nine healthy adult horses received a single 0.5-mg/kg dose of KT via each route of admi...
Analysis of metronidazole in equine plasma using liquid chromatography/tandem mass spectrometry and high-resolution accurate mass spectrometry.
Rapid communications in mass spectrometry : RCM    September 26, 2015   Volume 29, Issue 8 753-763 doi: 10.1002/rcm.7158
Ilomuanya M, Uboh C, Ciallella J, Li X, Liu Y, Ifudu N, Azubuike C, Igwilo C.Treatment of racehorses with bicarbonate solutions to manage acidosis and muscle cramps prior to competition is banned in Pennsylvania (PA). Use of excess bicarbonate in horses causes diarrhea, requiring treatment with an antibiotic such as metronidazole (MTNZ). At present no method exists for detecting MTNZ in equine plasma. Thus, a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the detection, quantification and confirmation of MTNZ was developed. Methods: The analyte was recovered from plasma by liquid-liquid extraction using methyl tert-butyl ether and separated on an ...
Electroencephalogram of Healthy Horses During Inhaled Anesthesia.
Journal of veterinary internal medicine    September 16, 2015   Volume 30, Issue 1 304-308 doi: 10.1111/jvim.13613
Williams DC, Aleman MR, Brosnan RJ, Fletcher DJ, Holliday TA, Tharp B, Kass PH, Steffey EP, LeCouteur RA.Previous study of the diagnostic validity of electroencephalography (EEG) to detect abnormalities in equine cerebral cortical function relied on the administration of various drugs for sedation, induction, and maintenance of general anesthesia but used identical criteria to interpret recordings. Objective: To determine the effects of 2 inhalation anesthetics on the EEG of healthy horses. Methods: Six healthy horses. Methods: Prospective study. After the sole administration of one of either isoflurane or halothane at 1.2, 1.4, and 1.6 times the minimum alveolar concentration, EEG was recorded d...
Economic assessment of FEC-based targeted selective drenching in horses.
Veterinary parasitology    September 14, 2015   Volume 214, Issue 1-2 159-166 doi: 10.1016/j.vetpar.2015.09.006
Sallé G, Cortet J, Koch C, Reigner F, Cabaret J.In the face of an increased prevalence of drug-resistant cyathostomin populations, a targeted selective treatment (TST) strategy based on Faecal Egg Counts (FECs) has been proposed as an alternative management strategy. However, associated costs may be a barrier to the uptake of this strategy. Our study aims to provide an economic assessment of FEC-based TST. FECs were determined in a Welsh pony herd thrice a year from 2010 to 2014. This database was used to explore the impact of FEC price, sampling strategy (individual or pooled) and labour-associated costs. Drug price was set at the cheapest...
The detection of a synthetic Interleukin-1 receptor antagonist peptide in a seized product from a racing stable.
Drug testing and analysis    September 11, 2015   Volume 8, Issue 9 957-965 doi: 10.1002/dta.1869
Levina V, Timms M, Vine J, Steel R.A synthetic Interleukin-1 receptor antagonist peptide with the sequence Acetyl-Phe-Glu-Trp-Thr-Pro-Gly-Tyr-Trp-Gln-Pro-Tyr-Ala-Leu-Pro-Leu-OH has been identified in a vial seized during a stable inspection. The use of peptide-based Interleukin-1 receptor antagonists as anti-inflammatory agents has not been previously reported, making this peptide the first in a new class of sports doping peptides. The peptide has been characterized by high-resolution mass spectrometry and a detection method developed based on solid-phase extraction and liquid chromatography - triple quadrupole mass spectrometr...
Propofol protects against opioid-induced hyperresponsiveness of airway smooth muscle in a horse model of target-controlled infusion anaesthesia.
European journal of pharmacology    September 11, 2015   Volume 765 463-471 doi: 10.1016/j.ejphar.2015.09.007
General anaesthesia in horses is associated with elevated mortality rate in subjects suffering of heaves. Target-controlled infusion (TCI) of sedative-hypnotic medications and opioids represents a total intravenous anaesthesia (TIVA) method validated in veterinary medicine. Since there are no data concerning the impact of these classes of drugs in inducing bronchial hyperresponsiveness (BHR) in horses, the aim of this study was to investigate the effect propofol and remifentanil on the contractile response of equine airway smooth muscle. The influence of propofol and remifentanil on the contra...
Macrolide-induced hyperthermia in foals: Role of impaired sweat responses.
Equine veterinary journal    September 7, 2015   Volume 48, Issue 5 590-594 doi: 10.1111/evj.12481
Stieler AL, Sanchez LC, Mallicote MF, Martabano BB, Burrow JA, MacKay RJ.The mechanism of hyperthermia, a potentially fatal adverse effect of erythromycin treatment of foals, is unknown. Objective: To determine the cause of erythromycin-associated hyperthermia. It was hypothesised that the normal sweat response of foals is impaired by treatment with erythromycin. Methods: Blinded, crossover study in 10 healthy pony foals. Methods: Foals kept in stalls were given either erythromycin (25 mg/kg bwt orally, 3 times daily) or control for 10 days then turned out for a further 10 days. Quantitative intradermal terbutaline sweat tests were performed on Days 1 (baseline)...
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