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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.
Detomidine reduces isoflurane anesthetic requirement (MAC) in horses. To quantitate the dose- and time-related magnitude of the anesthetic sparing effect of, and selected physiological responses to detomidine during isoflurane anesthesia in horses. Methods: Randomized cross-over study. Methods: Three, healthy, young adult horses weighing 485 ± 14 kg. Methods: Horses were anesthetized on two occasions to determine the minimum alveolar concentration (MAC) of isoflurane in O and then to measure the anesthetic sparing effect (time-related MAC reduction) following IV detomidine (0.03 and 0.06 mg kg). Selected common measures of cardiopulmonary function, blood glucos...
Serum concentrations and effects of detomidine delivered orally to horses in three different mediums. To compare the effect of orally delivered detomidine on head posture when administered alone or in combination with two different food items, and to determine the serum concentrations of detomidine after oral delivery. Methods: Prospective randomized experimental study. Methods: Fifteen adult grade mares weighing 328-537 kg. Methods: The horses were randomly assigned to one of the three treatment groups (five horses each). The groups were given detomidine (0.06 mg kg): alone; mixed with 3 mL of an apple sauce and gum mixture; or mixed with 3 mL molasses. Head droop, measured before treatment a...
Behavioral responses following eight anesthetic induction protocols in horses. To compare behavioral characteristics of induction and recovery in horses anesthetized with eight anesthetic drug protocols. Methods: Randomized prospective experimental study. Methods: Eight horses, 5.5 ± 2.4 years (mean ± SD) of age, and weighing 505 ± 31 kg. Methods: After xylazine pre-medication, each of eight horses was anesthetized on four occasions using one of eight different anesthetic induction protocols which incorporated various combinations of ketamine (KET), propofol (PRO), and thiopental (THIO): THIO 8 mg kg; THIO 6 mg kg + PRO 0.5 mg kg; THIO 4 mg kg + PRO 1 mg kg; THIO 2 mg...
Quantification of dimethylsulfoxide (DMSO) in equine plasma and urine using HILIC-MS/MS. This paper describes quantitative methods for the determination of dimethylsulfoxide (DMSO) in equine plasma and urine based on simple precipitation and dilution followed by hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry (HILIC-MS/MS). DMSO is a polar solvent with analgesic and anti-inflammatory properties. Its pharmacological features make it prohibited in horse racing. However, since DMSO is naturally present in the horses' environment, international threshold values have been implemented for plasma and urine (1 and 15 µg/mL, respectively). Previously pr...
Effects of Firocoxib, Flunixin Meglumine, and Phenylbutazone on Platelet Function and Thromboxane Synthesis in Healthy Horses. Determine the effects of nonsteroidal anti-inflammatory drugs (NSAID) on platelet function and thromboxane synthesis immediately after drug administration and following 5 days of NSAID administration in healthy horses. Methods: Randomized cross-over study. Methods: Healthy adult horses (n=9; 6 geldings and 3 mares). Methods: Horses received either flunixin meglumine (1.1 mg/kg IV every 12 hours), phenylbutazone (2.2 mg/kg IV every 12 hours), or firocoxib (loading dose of 0.27 mg/kg IV on day 1, then 0.09 mg/kg IV every 24 hours for 4 days) for a total of 5 days. Blood samples were collected pr...
Selective inhibition of Sarcocystis neurona calcium-dependent protein kinase 1 for equine protozoal myeloencephalitis therapy. Sarcocystis neurona is the most frequent cause of equine protozoal myeloencephalitis, a debilitating neurological disease of horses that can be difficult to treat. We identified SnCDPK1, the S. neurona homologue of calcium-dependent protein kinase 1 (CDPK1), a validated drug target in Toxoplasma gondii. SnCDPK1 shares the glycine "gatekeeper" residue of the well-characterized T. gondii enzyme, which allows the latter to be targeted by bumped kinase inhibitors. This study presents detailed molecular and phenotypic evidence that SnCDPK1 can be targeted for rational drug development. Recombinant ...
Doping control analysis of anabolic steroids in equine urine by gas chromatography-tandem mass spectrometry. Anabolic steroids are banned substances in equine sports. Gas chromatography-mass spectrometry (GC-MS) has been the traditional technique for doping control analysis of anabolic steroids in biological samples. Although liquid chromatography-mass spectrometry (LC/MS) has become an important technique in doping control, the detection of saturated hydroxysteroids by LC-MS remains a problem due to their low ionization efficiency under electrospray. The recent development in fast-scanning gas-chromatography-triple-quadrupole mass spectrometry (GC-MS/MS) has provided a better alternative with a sign...
Use of large-scale veterinary data for the investigation of antimicrobial prescribing practices in equine medicine. As antimicrobial resistant bacterial strains continue to emerge and spread in human and animal populations, understanding prescription practices is key in benchmarking current performance and setting goals. Antimicrobial prescription (AP) in companion veterinary species is widespread, but is neither monitored nor restricted in the USA and Canada. The veterinary use of certain antimicrobial classes is discouraged in some countries, in the hope of preserving efficacy for serious human infections. Objective: The aim of this study was to ascertain the rate of prescription of a number of 'reserved'...
Confirmatory analysis of etanercept in equine plasma by LC-MS for doping control. Etanercept is a protein-based medication for the treatment of human patients with rheumatoid arthritis and other autoimmune-based diseases; its pharmacological action is to inhibit and antagonize tumour necrosis factor alpha. Etanercept was rumoured to be used in horse racing in North America. To detect such use, the aim of this study was to develop a liquid chromatography-mass spectrometry (LC-MS) method for confirmation of etanercept in equine plasma. Etanercept was extracted from plasma by anti-human IgG antibody linked to magnetic beads. The analyte was reduced and alkylated, and then dige...
The effects of dose and diet on the pharmacodynamics of omeprazole in the horse. Conflicting data are presented in the current literature regarding the efficacy of omeprazole for suppressing gastric acidity in the horse. Objective: The objective of this study was to investigate the duration of intraday acid suppression achieved with two doses of omeprazole under two different dietary conditions. Methods: A four-way crossover design. Methods: Six adult Thoroughbred horses instrumented with percutaneous gastrotomy tubes were used. Intragastric pH was measured for continuous 23 h periods (08.00-07.00 h) for six consecutive days (Days 0-5). Baseline data was recorded on Day 0 ...
Pharmacokinetics of dextromethorphan and its metabolites in horses following a single oral administration. Dextromethorphan is an N-methyl-D-aspartate (NMDA) non-competitive antagonist commonly used in human medicine as an antitussive. Dextromethorphan is metabolized in humans by cytochrome P450 2D6 into dextrorphan, which is reported to be more potent than the parent compound. The goal of this study is to describe the metabolism of and determine the pharmacokinetics of dextromethorphan and its major metabolites following oral administration to horses. A total of 23 horses received a single oral dose of 2 mg/kg. Blood samples were collected at time 0 and at various times up to 96 h post drug ad...
Equine hepatocytes: isolation, cryopreservation, and applications to in vitro drug metabolism studies. Despite reports of the successful isolation of primary equine hepatocytes, there are no published data regarding the successful cryopreservation of these isolated cells. In this study, a detailed description of the procedures for isolation, cryopreservation, and recovery of equine hepatocytes are presented. Furthermore, the intrinsic clearance (Cl) and production of metabolites for three drugs were compared between freshly isolated and recovered cryopreserved hepatocytes. Primary equine hepatocytes were isolated using a two-step collagenase perfusion method, with an average cell yield of 2.47Â...
Comparative pharmacokinetics of minocycline in foals and adult horses. The objective of this study was to compare the pharmacokinetics of minocycline in foals vs. adult horses. Minocycline was administered to six healthy 6-Â to 9-week-old foals and six adult horses at a dose of 4Â mg/kg intragastrically (IG) and 2Â mg/kg intravenously (i.v.) in a cross-over design. Five additional oral doses were administered at 12-h intervals in foals. A microbiologic assay was used to measure minocycline concentration in plasma, urine, synovial fluid, and cerebrospinal fluid (CSF). Liquid chromatography-tandem mass spectrometry was used to measure minocycline concentrations in ...
Ivermectin failure in the control of Oxyuris equi in a herd of ponies in France. Drug resistance in equine gastro-intestinal parasitic nematodes has been reported throughout the world. While the focus is usually put on cyathostomins, observations of macrocylic lactone failure against Oxyuris equi have accumulated over the last decade. Here we report the failure of ivermectin in the control of O. equi in an experimental Welsh pony herd. In a first trial, 6 ponies previously drenched with moxidectin and showing patent O. equi infections were administered ivermectin and subsequently monitored for O. equi egg excretion over one month. This trial demonstrated a failure of iverm...
Comparison of the pharmacokinetics of two formulations of hydroxyethyl starch in healthy horses. A lower molecular weight and molar substitution formulation (130/0.4) of hydroxyethyl starch solution has been shown to have a more sustained effect on COP and similar hemodynamic effects as a higher molecular weight and molar substitution formulation (600/0.75) in healthy horses. In humans, these pharmacodynamic characteristics are coupled with more rapid clearance and decreased adverse coagulation effects and accumulation. The objective of this study was to determine and compare the pharmacokinetics of these two formulations in horses. Eight healthy horses were given a 10Â mL/kg bolus of eac...
Plasma and synovial fluid pharmacokinetics of cefquinome following the administration of multiple doses in horses. The plasma and synovial fluid pharmacokinetics and safety of cefquinome, a 2-amino-5-thiazolyl cephalosporin, were determined after multiple intravenous administrations in sixteen healthy horses. Cefquinome was administered to each horse through a slow i.v. injection over 20 min at 1, 2, 4, and 6 mg/kg (n = 4 horses per dose) every 12 h for 7 days (a total of 13 injections). Serial blood and synovial fluid samples were collected during the 12 h after the administration of the first and last doses and were analyzed by a high-performance liquid chromatography assay. The data were evaluate...
Pharmacokinetic and pharmacodynamics of xylazine administered to exercised thoroughbred horses. There is limited data describing xylazine serum concentrations in the horse and no reports of concentrations beyond 24 hours. The primary goal of the study reported here was to update the pharmacokinetics of xylazine following intravenous (IV) administration in order to assess the applicability of current regulatory recommendations. Pharmacodynamic parameters were determined using PK-PD modeling. Sixteen exercised adult Thoroughbred horses received a single IV dose of 200 mg of xylazine. Blood and urine samples were collected at time 0 and at various times for up to 96 hours and analyzed...
Dextromethorphan and debrisoquine metabolism and polymorphism of the gene for cytochrome P450 isozyme 2D50 in Thoroughbreds. OBJECTIVE To characterize polymorphisms of the gene for cytochrome P450 isozyme 2D50 (CYP2D50) and the disposition of 2 CYP2D50 probe drugs, dextromethorphan and debrisoquine, in horses. ANIMALS 23 healthy horses (22 Thoroughbreds and 1 Standardbred). PROCEDURES Single-nucleotide polymorphisms (SNPs) in CYP2D50 were identified. Disposition of dextromethorphan (2 mg/kg) and debrisoquine (0.2 mg/kg) were determined after oral (dextromethorphan) or nasogastric (debrisoquine) administration to the horses. Metabolic ratios of plasma dextromethorphan and total dextrorphan (dextrorphan plus dextrorph...
[Historical development of drug testing in Swiss equestrian sports]. The goal of this study was to describe the development of equine drug testing in horses in Switzerland. This was achieved through evaluation of a film made by the Institute of Forensic Medicine at the University of Basel entitled 'Doping von Rennpferden' [Doping of Race Horses], toxicological detection, 1962', the analysis of doping test results of the Swiss Equestrian Federation and by interviewing individuals of various professions who were involved in equine drug testing at the time. The study compares early and modern methods of drug testing and highlights the changes in the attitude of eq...
Differential expression of skeletal muscle genes following administration of clenbuterol to exercised horses. Clenbuterol, a beta2-adrenergic receptor agonist, is used therapeutically to treat respiratory conditions in the horse. However, by virtue of its mechanism of action it has been suggested that clenbuterol may also have repartitioning affects in horses and as such the potential to affect performance. Clenbuterol decreases the percent fat and increases fat-free mass following high dose administration in combination with intense exercise in horses. In the current study, microarray analysis and real-time PCR were used to study the temporal effects of low and high dose chronic clenbuterol administr...
A cluster of trace-concentration methamphetamine identifications in racehorses associated with a methamphetamine-contaminated horse trailer: A report and analysis. Three low concentration methamphetamine "positive" tests were linked to use of a methamphetamine-contaminated trailer to transport the affected horses. This incident establishes methamphetamine as a human-use substance that can inadvertently enter the environment of racing horses, resulting in urinary methamphetamine "positives;" an interim regulatory cut-off of 15 ng/mL for methamphetamine in post-race urine is proposed. Trois tests «positifs» de faibles concentrations de méthamphétamine ont été associés à l’utilisation d’une remorque contaminée par les méthamphétamines qui é...
Ovicidal efficacy of fenbendazole after treatment of horses naturally infected with cyathostomins. The ovicidal activity of benzimidazole (BZ) anthelmintics is unique and not seen in other drug classes. Such ovicidal efficacy is not widely reported for equine cyathostomins, nor has this activity been tested in the face of BZ resistance. Although the product label states that fenbendazole is for use against BZ-susceptible cyathostomins, susceptibility testing is rarely performed. In this field-based study, the ovicidal efficacy of fenbendazole in horses (n=39) harbouring BZ-resistant cyathostomins was compared when dosed at 7.5mg/kg body weight (BW) orally, as a single dose per os (n=21) or ...
Pharmacokinetic profiles of the active metamizole metabolites in healthy horses. Metamizole (MT) is an analgesic and antipyretic drug labelled for use in humans, horses, cattle, swine and dogs. MT is rapidly hydrolysed to the active primary metabolite 4-methylaminoantipyrine (MAA). MAA is formed in much larger amounts compared with other minor metabolites. Among the other secondary metabolites, 4-aminoantipyrine (AA) is also relatively active. The aim of this research was to evaluate the pharmacokinetic profiles of MAA and AA after dose of 25Â mg/kg MT by intravenous (i.v.) and intramuscular (i.m.) routes in healthy horses. Six horses were randomly allocated to two equally...
Preliminary study of tissue concentrations of penicillin after local administration into the guttural pouches in four healthy horses. Treatment of subclinical carriers of Streptococcus equi subsp. equi with a gelatine-penicillin formulation deposited in the guttural pouch has been empirically proposed, but data on local tissue penicillin concentrations after treatment are lacking. Methods: We analysed tissue levels of penicillin after administration into the guttural pouches of four healthy horses. Two horses received local treatment with gelatine-penicillin and two horses received local treatment with an intramammary formulation of penicillin. Tissues were harvested for analysis either 12 or 24 h later. Conclusions: Resul...
Analysis of phenylbutazone residues in horse tissues with and without enzyme-hydrolysis by LC-MS/MS. Phenylbutazone (PBZ) is permitted to be used for the treatment of musculoskeletal pain and inflammation in race horses but it is not approved for use in horses destined for human consumption. In a recent study initiated in our laboratory to study the disposition of PBZ and its oxyphenbutazone (OXPBZ) metabolite in equine tissues, we compared the effect of an additional enzymatic hydrolysis step with ß-glucuronidase on the results of the analysis for PBZ without enzymatic hydrolysis. Incurred tissue samples obtained from a female horse dosed with PBZ at 8.8 mg/kg for 3 days and sacrificed ...
Evolution of in vitro antimicrobial resistance in an equine hospital over 3 decades. This study identified antimicrobial resistance patterns of commonly isolated bacteria at the Equine Hospital of the Université de Montréal between 2007 and 2013, and compared the results with the resistance patterns observed in tests performed in previous decades in the same hospital. A total of 396 antimicrobial susceptibility tests were analyzed by the Kirby-Bauer method during the period 2007 to 2013 and compared to 233 and 255 tests completed in 1986 to 1988 and 1996 to 1998, respectively. The most common bacteria were Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) and Escher...
Drug Residues after Intravenous Anesthesia and Intrathecal Lidocaine Hydrochloride Euthanasia in Horses. Intrathecal lidocaine hydrochloride under general anesthesia has been used as an alternative method of euthanasia in equids. Carnivore, scavenger, and even human consumption of horse meat from carcasses have been anecdotally reported in rural areas after this method of euthanasia. The presence of drug residues in horse meat has not been investigated. Objective: To investigate if drug residues are found in horse tissues and determine their concentrations. Methods: Of 11 horses requiring euthanasia for medical reasons. Methods: Prospective descriptive study. Horses were anesthetized with total I...
Studies of the pharmacokinetic profile, in vivo efficacy and safety of injectable altrenogest for the suppression of oestrus in mares. To investigate the efficacy and safety of the long-acting altrenogest injection (NV Readyserve® injection) for horses. Methods: A single-dose pharmacokinetic (PK) study was conducted. The in vivo efficacy study was a blinded, repeated measures design evaluating behaviour scores. The safety study was a non-blinded, controlled, parallel-group, randomised-block design as per the VICH protocol. Methods: In the PK study, serial blood samples were obtained for analysis of plasma altrenogest for 150 h following the injection and a non-compartmental PK analysis was performed. For the efficacy study, ...
Influence of commonly used pharmaceutical agents on equine bone marrow-derived mesenchymal stem cell viability. To provide evidence to support recommendations regarding the co-administration of drugs with mesenchymal stem cell (MSC) therapy. Objective: To determine the influence of sedatives, local anaesthetic and corticosteroids on MSC viability and proliferation, in comparison to somatic cells derived from tendon (TDCs). Methods: In vitro cell culture. Methods: MSCs (n = 3) and TDCs (n = 2) were cultured in media containing a clinically relevant dose range of xylazine, romifidine, detomidine and butorphanol, mepivacaine, methylprednisolone, or triamcinolone acetonide. Cell viability in suspension cult...
