Topic:Pharmaceuticals
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.
Sporadic worldwide “clusters” of feed driven Zilpaterol identifications in racing horses: a review and analysis. Zilpaterol is a β2-adrenergic agonist medication approved in certain countries as a cattle feed additive to improve carcass quality. Trace amounts of Zilpaterol can transfer to horse feed, yielding equine urinary "identifications" of Zilpaterol. These "identifications" occur because Zilpaterol is highly bioavailable in horses, resistant to biotransformation and excreted as unchanged Zilpaterol in urine, where it has a 5 day or so terminal half-life.In horses, urinary steady-state concentrations are reached 25 days (5 half-lives) after exposure to contaminated feed. Zilpaterol readily presen...
A quantitative method for the simultaneous detection of SR9009 and SR9011 in equine plasma using liquid chromatography-electrospray ionization-tandem mass spectrometry. SR9009 and SR9011 are metabolic modulators pharmacologically targeting REV-ERB receptors as synthetic agonists. A liquid chromatography-tandem mass spectrometry method for the detection of SR9009 and SR9011 in equine plasma was developed and validated. Plasma samples were pretreated by protein precipitation with methanol and were loaded onto an ACQUITY ultra performance liquid chromatography high-strength silica C18 column (2.1 × 150 mm, 1.8 μm) for chromatographic separation. The mobile phase consisted of 5-mM ammonium formate (pH 3.0) in distilled water and 0.1% formic acid in ac...
Pharmacokinetics of glaucine after intravenous and oral administrations and detection of systemic aporphine alkaloids after ingestion of tulip poplar shavings in horses. Glaucine, an aporphine alkaloid with anti-tussive, anti-inflammatory, and anti-nociceptive properties, has been identified in post-race samples from racehorses. To investigate pharmacokinetics of glaucine in horses, a three-way crossover study of intravenous and oral glaucine (0.1 mg/kg) and orally administered tulip poplar shavings (50 g shavings = 0.001 mg/kg glaucine) was performed in six horses. A two-compartment model best described IV administration with alpha ( ) and beta ( ) half-life lives of 0.3 (0.1-0.7) and 3.1 (2.4-7.8) h, respectively. The area under the curve ( ) was ...
Intelligence benefit of the 3-methoxytyramine to tyramine ratio in equine urine. Equine urine analysis has evolved over time to detect thousands of urinary compounds for doping control in the horse racing industry. The longitudinal assessment of 3-methoxytyramine to tyramine ratio (3-MT/T) values in equine urine by GC-MS profiling was investigated to support the Racing NSW Equine Biological Passport (EBP) for detection of dopaminergic manipulation in racehorses. This involved comparison of routine urine samples to administration studies of Sinemet, a common Parkinson's disease medication containing levodopa. Using an endogenous reference compound (ERC) in a urinary ratio e...
Equine metabolism of the growth hormone secretagogue MK-0677 in vitro and in urine and plasma following oral administration. Ibutamoren mesylate, or MK-0677, is an orally active, nonpeptide growth hormone secretagogue that has been developed to stimulate excretion of endogenous growth hormone. It has been evaluated for the treatment of a range of clinical conditions but is not available therapeutically. Nonetheless, MK-0677 is widely available to purchase online, sold as 'supplement' products. The mode of action and relative ease of purchase make MK-0677 a potential threat with regard to sports doping. The aim of this study was to investigate the metabolism of MK0677 in the horse following in vitro incubation and or...
Long-term monitoring of IOX4 in horse hair and its longitudinal distribution with segmental analysis using liquid chromatography/electrospray ionization Q Exactive high-resolution mass spectrometry for the purpose of doping control. IOX4, a hypoxia-inducible factor stabilizer, is classified as a banned substance for horses in both horse racing and equestrian sports. We recently reported the pharmacokinetic profiles of IOX4 in horse plasma and urine and also identified potential monitoring targets for the doping control purpose. In this study, a long-term longitudinal analysis of IOX4 in horse hair after a nasoesophageal administration of IOX4 (500 mg/day for 3 days) to three thoroughbred mares is presented for the first time for controlling the abuse/misuse of IOX4. Six bunches of mane hair were collected at 0 (pre), ...
Measurements of hydrocortisone and cortisone for longitudinal profiling of equine plasma by liquid chromatography-tandem mass spectrometry. The conventional detection of exogenous drugs in equine doping samples has been used for confirmation and subsequent prosecution of participants responsible. In recent years, alternative methods using indirect detection have been investigated due to the expanding number of pharmaceutical agents available with the potential of misuse. The monitoring of endogenous biomarkers such as hydrocortisone (HC) has been studied in equine urine with an international threshold of 1 μg/ml established; however, there is no current threshold for equine plasma. The aim of this research was to investigate pl...
Profiling Urinary Sulfate Metabolites With Mass Spectrometry. The study of urinary phase II sulfate metabolites is central to understanding the role and fate of endogenous and exogenous compounds in biological systems. This study describes a new workflow for the untargeted metabolic profiling of sulfated metabolites in a urine matrix. Analysis was performed using ultra-high-performance liquid chromatography-high resolution tandem mass spectrometry (UHPLC-HRMS/MS) with data dependent acquisition (DDA) coupled to an automated script-based data processing pipeline and differential metabolite level analysis. Sulfates were identified through -means clustering...
Acquisition and use of analgesic drugs by horse owners in the United States. Little is known about the acquisition and use of equine analgesic drugs by horse owners in the United States (US). Objective: To determine factors associated with possession of analgesic drugs by horse owners in the US or with analgesic drug acquisition from sources noncompliant with a valid veterinarian-client-patient (VCPR) relationship. Methods: Cross-sectional survey. Methods: An internet-based questionnaire included items related to experiences with horses and equine analgesic drugs. Factors associated with possession of ≥5 types of analgesic drugs and with the acquisition of drugs from...
Sucrose Acetate Isobutyrate (SAIB) as a Delivery Vehicle for Estradiol and Sulpiride: Evaluation of Endocrine Responses in Geldings and Ovarian Response in Seasonally Anovulatory Mares. Sulpiride in vegetable shortening (VS) stimulates prolactin in horses for up to 10 days. Although effective, a pharmaceutical grade vehicle is needed for clinical application of sulpiride in horses. Sucrose acetate isobutyrate (SAIB), a hydrophobic polymer, may be an alternative to VS. Four in vivo experiments assessed the efficacy of SAIB for delivery of sulpiride, estradiol cypionate (ECP), and estradiol benzoate (EB). The first three studies utilized geldings to compare prolactin and luteinizing hormone (LH) concentrations between sulpiride delivered in VS and SAIB, and ECP or EB delivered ...
Non-steroidal anti-inflammatory drugs in equine orthopaedics. Orthopaedic disorders are commonly encountered in equine veterinary medicine, and non-steroidal anti-inflammatory drugs (NSAIDs) play an important role in the management of many equine orthopaedic disorders. There are multiple NSAIDs available for use in horses, including both non-selective and selective NSAIDS, and the body of literature evaluating the efficacy of these medications, their effects on normal and inflamed musculoskeletal tissues, and their side effects is broad. This review aims to summarise the current literature on the use of NSAIDs for equine orthopaedic disorders and examine...
Therapeutic Potential of Metabolites from Lactobacillus rhamnosus and Mare’s Milk in the Treatment of Dysbiosis. Ulcerative colitis is an inflammatory bowel disease that forms ulcerations in the mucous membrane of the colon and rectum, in which gut microbiota plays a pivotal role in its pathogenesis. Agents modulating microbial dysbiosis caused by colitis can help in the remission of this disease. The current study describes the potential therapeutic effects of active metabolites from Lactobacillus rhamnosus and mare's milk which have potential therapeutic values on the intestinal microbiota and proinflammatory cytokines. The analysis of the V1-V3 16S rDNA site revealed significant changes in the intesti...
Prevalence and treatment of gastric ulcers in Thoroughbred racehorses of Korea. Gastric ulcer is one of the prevalent diseases in racehorses. However, it has not been recognized as important in Korea, and drugs used to treat gastric ulcers are included in the doping test list, so they are not allowed to be administered to racehorses in training. Objective: This study was performed 1) to investigate the prevalence and the severity of gastric ulcers in Thoroughbred racehorses in Korea, 2) to confirm the therapeutic effect of ranitidine and omeprazole, and 3) to compare the efficacy between ranitidine and omeprazole. Methods: Forty-nine horses were randomly recruited, and ga...
Pharmacokinetics and pharmacodynamics of oral and intravenous metoprolol tartrate in clinically healthy horses. Cardiac drugs with defined pharmacological parameters in horses are limited. The objective of this study was to characterize the pharmacokinetic properties and cardiovascular effects of intravenous and oral metoprolol tartrate (MET) in horses. In a 2-period randomized cross-over design, MET was administered IV (0.04 mg/kg) and PO (6 mg/kg) once to six healthy adult horses. Horses were monitored via continuous telemetry and non-invasive blood pressure (NIBP). Blood samples were serially collected for 72 h post-administration, and concentrations were determined by LC-MS/MS. Pharmacokinetics w...
Identification of equine in vitro metabolites of seven non-steroidal selective androgen receptor modulators for doping control purposes. Selective androgen receptor modulators, SARMs, are a large class of compounds developed to provide therapeutic anabolic effects with minimal androgenic side effects. A wide range of these compounds are available to purchase online and thus provide the potential for abuse in sports. Knowledge of the metabolism of these compounds is essential to aid their detection in doping control samples. In vitro models allow a quick, cost-effective response where administration studies are yet to be carried out. In this study, the equine phase I metabolism of the non-steroidal SARMs GSK2881078, LGD-2226, LG...
In vitro studies of hypoxia inducible factor-prolyl hydroxylase inhibitors daprodustat, desidustat, and vadadustat for equine doping control. Performance-enhancing substances and methods have become a serious problem in competitive sports. The hypoxia-inducible factor (HIF) stabilizers can enhance the organism's capacity for molecular oxygen transport and are likely to be abused as performance-enhancing agents in sports. This paper describes the metabolic conversion of the popular hypoxia inducible factor-prolyl hydroxylase (HIF-PH) inhibitors, namely, daprodustat, desidustat, and vadadustat using equine liver microsomes, determined on a QExactive high-resolution mass spectrometer. During this study, a total of 10 metabolites for da...
Development of a Standardized Microflow LC Gradient to Enable Sensitive and Long-Term Detection of Synthetic Anabolic-Androgenic Steroids for High-Throughput Doping Controls. Synthetic androgenic anabolic steroids (AAS) are banned compounds and considered as major threats by both racing and sports international authorities. Hence, doping control laboratories are continually looking into analytical improvements to increase their detection capabilities, notably by means of emerging technologies. To enhance analytical performances for the detection of synthetic AAS such as stanozolol, specific chromatographic procedures have been developed using recent quaternary liquid chromatography technology originally designed for high-throughput standardized proteomics connected...
Study of cobalt doping control via various routes in thoroughbred horses. Cobalt is a substance that has been abused for athletic performance enhancement and has thus been prohibited by human and animal sports doping control authorities. However, because cobalt is present in humans and animals as a trace element, a certain level of cobalt is naturally present in their excretions. In the racing industry, cobalt is a controlled substance with a threshold concentration specified by the International Agreement on Breeding, Racing and Wagering (IABRW) for international harmonization. Due to environmental and feed consumption differences among countries, regional cobalt c...
Pharmacokinetics of fluoxetine in horses following oral administration. This study aimed to investigate pharmacokinetics of fluoxetine in horses and validate a method for liquid chromatography mass spectrometry analysis of serum levels. Fluoxetine pharmacokinetics were determined using 10 healthy, adult horses. Fluoxetine pharmacokinetics following a single oral dose (0.25 mg/kg) were determined using blood samples collected prior to and at several time points over 7 days following administration. Serum concentrations of fluoxetine and its bioactive metabolite norfluoxetine were measured using liquid chromatography coupled to an accurate mass/high-resolution ma...
Comprehensive metabolic study of IOX4 in equine urine and plasma using liquid chromatography/electrospray ionization Q Exactive high-resolution mass spectrometer for the purpose of doping control. IOX4 is a hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitor, which was developed for the treatment of anemia by exerting hematopoietic effects. The administration of HIF-PHD inhibitors such as IOX4 to horses is strictly prohibited by the International Federation of Horseracing Authorities and the Fédération Équestre Internationale. To the best of our knowledge, this is the first comprehensive metabolic study of IOX4 in horse plasma and urine after a nasoesophageal administration of IOX4 (500 mg/day, 3 days). A total of four metabolites (three mono-hydroxylated IOX4 and one ...
Fundamentals of arrhythmogenic mechanisms and treatment strategies for equine atrial fibrillation. Atrial fibrillation (AF) is the most common pathological arrhythmia in horses. Although it is not usually a life-threatening condition on its own, it can cause poor performance and make the horse unsafe to ride. It is a complex multifactorial disease influenced by both genetic and environmental factors including exercise training, comorbidities or ageing. The interactions between all these factors in horses are still not completely understood and the pathophysiology of AF remains poorly defined. Exciting progress has been recently made in equine cardiac electrophysiology in terms of diagnosis ...
Pharmacology of the Equine Foot: Medical Pain Management for Laminitis. One of the biggest challenges in managing laminitis in horses remains the control of pain. The best analgesic approach is a multimodal approach, including nonsteroidal anti-inflammatory drugs, opioids, and/or constant rate infusions of α-2 agonists, ketamine, and lidocaine. Recent literature indicates that amitriptyline and soluble epoxide hydrolase inhibitor might be beneficial. Clinically oriented studies will be needed if they have a place in laminitis pain management. The systemic pain control can be combined with local techniques such as long-acting local anesthetics or epidural catheter...
Detection of Methylphenidate in Equine Hair Using Liquid Chromatography-High-Resolution Mass Spectrometry. Methylphenidate is a powerful central nervous system stimulant with a high potential for abuse in horse racing. The detection of methylphenidate use is of interest to horse racing authorities for both prior to and during competition. The use of hair as an alternative sampling matrix for equine anti-doping has increased as the number of detectable compounds has expanded. Our laboratory developed a liquid chromatography-high-resolution mass spectrometry method to detect the presence of methylphenidate in submitted samples. Briefly, hair was decontaminated, cut, and pulverized prior to liquid-liq...
Pharmacokinetics of ceftiofur in the metacarpophalangeal joint after standing intravenous regional limb perfusion in horses. This study investigated the pharmacokinetics of ceftiofur after intravenous regional limb perfusion (IVRLP). Six horses were involved in 3 IVRLP sessions. For each session, operators with varying clinical experience placed the tourniquet. A wide-rubber tourniquet was applied in the antebrachium as 2 g of ceftiofur in a total volume of 100 mL was injected into the cephalic vein. Plasma and metacarpophalangeal synovial fluid samples were obtained to evaluate perfusate leakage and synovial fluid concentrations of ceftiofur over 24 h. Overall, mean plasma concentrations were not significantly diff...
Ciprofloxacin reduces tenocyte viability and proteoglycan synthesis in short-term explant cultures of equine tendon. Fluoroquinolones are an effective, broad-spectrum antibiotic used to treat an array of bacterial infections. However, they are associated with an increased risk of tendinopathy and tendon rupture even after discontinuation of treatment. This condition is known as fluoroquinolone-associated tendinopathy, the underlying mechanisms of which are poorly understood. While many factors may be involved in the pathophysiology of tendinopathies in general, changes in tenocyte metabolism and viability, as well as alteration of proteoglycan metabolism are prominent findings in the scientific literature. T...
Pharmacokinetic Profiles of Metamizole Metabolites after Intramuscular and Intravenous Administration in Healthy Arabian Horses. Metamizole sodium (MT) is an analgesic and antipyretic drug molecule used in humans, horses, cattle, swine, and dogs. Metamizole rapidly hydrolyzes and turns into methylamino antipyrine (MAA), an active primary metabolite of MT. The present study aims to determine the pharmacokinetic (PK) profiles of MT metabolites after intravenous (IV) and intramuscular (IM) administration into sex of Arabian horses (Equus ferus caballus) using a cross-over study design. The plasma samples were extracted by solid-phase extraction (SPE) method, and plasma concentrations of MT metabolites were analyzed by high...
Pharmacokinetics of thiamine (vitamin B1) in adult horses after administration of three single intravenous doses. Thiamine is a vital co-factor for several anti-inflammatory and antioxidant processes that are critical for mitigation of sepsis-associated inflammation, but pharmacokinetic (PK) analysis has not been reported in horses. We hypothesized that IV thiamine hydrochloride (TH) at increasing dosages would result in corresponding increases in plasma thiamine concentrations without causing adverse effects. A randomized cross-over study was performed in 9 healthy horses that each received TH at 5, 10, and 20 mg/kg IV. Blood was collected immediately prior to drug administration and at several time poi...
Pharmacokinetic properties of metamizole active metabolites in Northeastern Brazilian donkeys (Equus asinus). Metamizole (MT), also known as dipyrone, is an analgesic and antipyretic drug labeled for use in humans and domestic animals in some countries. As with other drugs, the administration of MT in donkeys is based on studies carried out with horses. In the present report, we aimed to determine the pharmacokinetics of the two main metamizole active metabolites (N-methyl-4-aminoantipyrine [MAA] and 4-aminoantipyrine [AA]) following 10 (M ) and 25 mg/kg (M ) IV metamizole doses in Northeast Brazilian donkeys (n = 10). Blood was collected at predetermined times within over 48 h; MAA and AA plasma ...
In vitro metabolism of the REV-ERB agonist SR-9009 and subsequent detection of metabolites in associated routine equine plasma and urine doping control samples. SR-9009 is a synthetic compound widely available to purchase online as 'supplement' products due to its potential performance-enhancing effects, presenting a significant threat with regard to doping control in sport. In vitro metabolism with equine liver microsomes was performed to identify potential targets for detection of SR-9009. Six metabolites were identified, with the most abundant consisting of N-dealkylated metabolites (M1-M3). The addition of the identified metabolites to high-resolution accurate mass databases resulted in a positive finding for the N-dealkylated metabolite M1 of SR-...