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Topic:Pharmacology
Pharmacology in horses involves the study and application of drugs and medications to diagnose, treat, and prevent diseases and conditions in equine species. This field encompasses the understanding of pharmacokinetics and pharmacodynamics specific to horses, including how drugs are absorbed, distributed, metabolized, and excreted by the equine body. Commonly studied pharmacological agents in horses include non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, sedatives, and anthelmintics. Research in equine pharmacology focuses on determining appropriate dosages, understanding drug interactions, and minimizing adverse effects. This page compiles peer-reviewed research studies and scholarly articles that investigate the efficacy, safety, and regulatory aspects of pharmacological interventions in equine veterinary practice.
Trazodone administration does not affect platelet concentration or function in horses. To determine the effect of a clinically relevant dose of trazodone on platelet count and function in healthy horses. Methods: Prospective, controlled, cross-over study. Methods: Ten healthy horses. Methods: Horses were administered either 7 mg/kg trazodone orally in corn syrup or an equal amount of corn syrup (control), every 12 h for 2 weeks. After 2 weeks, horses underwent at least a 2-week washout period before being administered the alternate treatment (trazodone or control). Blood was collected before the first treatment administration (day 0) and after 2 weeks of treatment for ...
Investigating the TASK1 potassium channel in equine atrial myocardium as a potential treatment target for atrial fibrillation. Atrial fibrillation (AF) is the most common clinically relevant arrhythmia in horses, with limited pharmacological treatment options in both veterinary and human medicine. TASK1 potassium channels represent a promising atrial-selective antiarrhythmic target, but their relevance in horses has not been established. To characterize equine TASK1 (eqTASK1) channels regarding structural conservation, electrophysiological function, pharmacological sensitivity, cardiac expression pattern and in vivo electrophysiological effects of TASK1 inhibition. Methods: Sixteen horses killed for non-cardiovascular...
Low-dose histrelin for ovulation induction in mares: a partially randomized crossover pilot study. This partially randomized crossover pilot study evaluated reduced doses of histrelin for ovulation induction in mares and compared intramuscular (IM) administration with pharmacopuncture at the Bai-hui and Yan-chi acupoints. Eleven mares were enrolled, of which nine completed all eight protocols and were included in the analyses. The protocols comprised 250 µg histrelin IM (standard dose), 75 µg IM, 25 µg IM, no intervention, saline at Bai-hui, saline at Yan-chi, 25 µg histrelin at Bai-hui, and 25 µg histrelin at Yan-chi. Ovulation was assessed by transrectal ultrasonography at sched...
Ivermectin enhances the transcription of pro-inflammatory cytokines in equine leukocytes stimulated with LPS and nigericin. Ivermectin has been reported to exert immunomodulatory effects on the innate immune system; however, the available evidence is contradictory, with both anti-inflammatory and, paradoxically, pro-inflammatory effects described depending on species, dose, and experimental context, while data specific to horses remain scarce. We hypothesised that ivermectin would exert a context-dependent immunomodulatory effect on equine leucocytes. To test this, total leucocytes isolated from six healthy horses were incubated with ivermectin (2 and 4 µg/mL) before stimulation with lipopolysaccharide (LPS) and n...
Effect of canagliflozin treatment on β-cell responsiveness in insulin-dysregulated horses: a 4-week, multi-arm, double-blind, randomized clinical trial. The sodium-glucose co-transporter 2 (SGLT2) inhibitor canagliflozin (CAN) decreases hyperinsulinemia in insulin-dysregulated (ID) horses, but its effects on pancreatic β-cell responsiveness to glucose are unknown. Objective: Compare the effects of 2 CAN dosages (0.6 and 1.2 mg/kg) with placebo (PBO) on β-cell responsiveness to IV glucose in ID horses using a graded glucose infusion (GGI) test. Methods: Forty-two privately-owned ID horses. Methods: Randomized, multicenter, double-blind, parallel-group, multi-arm, PBO-controlled study. Horses underwent GGI testing before and after 4 weeks of...
Proof of Concept for Open Flow Microperfusion for Intratumoural Drug Administration in Equine Cutaneous Neoplasia. Intratumoural drug delivery can achieve high local therapeutic exposure while limiting systemic effects, but heterogeneous distribution may compromise treatment efficacy and precision. This proof-of-concept study investigated open flow microperfusion (OFM) as a novel platform for local delivery of tigilanol tiglate (TT), an intratumoural antineoplastic agent with immunomodulatory and vascular-disrupting effects. Four horses with histologically confirmed cutaneous neoplasia (three sarcoids and one squamous cell carcinoma) underwent OFM using TT concentrations of 0.01-0.04 mg/mL delivered at 9 ...
The effect of ertugliflozin on serum insulin and glucose in healthy horses receiving dexamethasone. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) can be used to manage insulin dysregulation (ID). Their effect on corticosteroid-induced ID is unknown. Objective: Evaluate effects of ertugliflozin on serum insulin and glucose concentrations in horses receiving dexamethasone (DEX). We hypothesized that DEX would induce ID and ertugliflozin coadministration would mitigate that effect. Methods: Seven healthy horses. Methods: Randomized crossover design; horses received DEX (0.06 mg/kg IV q48h; DEX)or ertugliflozin (0.05 mg/kg PO q24h) plus DEX (SGLT-2i group) for seven days. Oral sugar (OST...
Oral Mosapride Attenuates Gastrointestinal Dysmotility During Experimental Endotoxemia in Horses: A Randomized, Blinded Crossover Study. Endotoxemia is a major contributor to gastrointestinal hypomotility and postoperative ileus in horses. This study investigated whether oral mosapride retained prokinetic activity during acute lipopolysaccharide (LPS)-induced endotoxemia. Seven healthy adult horses were enrolled in a randomized, blinded, three-period crossover trial and received LPS alone, mosapride alone (MOSA), or LPS plus mosapride (LPS + MOSA), with a 14-day washout interval between periods. Mosapride was administered orally at 2 mg/kg, whereas endotoxemia was induced by an intravenous infusion of O55:B5 LPS (0.03 µg/kg) ...
Effects of constant rate infusion of a fixed-dose combination of medetomidine and vatinoxan on sedation, cardiorespiratory variables, and gastrointestinal activity in standing Thoroughbred horses. A fixed-dose combination of medetomidine (MED) and vatinoxan (VTX), a peripherally selective α2-adrenoceptor antagonist, is commercially available, but its constant rate infusion (CRI) has not been evaluated. Objective: To compare the sedative effects, cardiorespiratory variables, and gastrointestinal activity of MED-VTX and MED-atipamezole (ATIP) with MED alone in Thoroughbred horses. Methods: Six healthy Thoroughbreds underwent a blinded three-treatment, three-period crossover study. Horses received MED (7 μg/kg IV; 5 μg/kg/h CRI for 60 min) alone (gM), with VTX (140 μg/kg IV; 100 μg/kg...
Residual contamination in nebulization medication cups after corticosteroid administration: an in vitro assessment with implications for equine doping control. Nebulization is increasingly used to administer respiratory medications in horses. However, the potential for residual contamination in medication cups after administering regulated substances raises concerns about inadvertent doping. Objective: To evaluate whether medication cups used for nebulization of corticosteroids can subsequently be used for administration of non-regulated substances without detectable carryover. Methods: In vitro experimental study. Methods: Three corticosteroids (budesonide, dexamethasone, fluticasone propionate) were nebulized using Flexineb™ medication cups. Foll...
Millimeter‑segmental analysis of individual equine mane hairs by LC/HRMS for revealing chronological drug distribution in anti‑doping investigations. Millimeter‑segmental analysis offers substantially improved temporal resolution over conventional bulk hair testing, yet no validated workflow has been established for equine mane hair. This proof‑of‑concept study presents the first liquid chromatography/high‑resolution mass spectrometry (LC/HRMS)‑based millimeter‑segmental workflow optimized for equine anti‑doping investigations. Mane hairs collected up to six months after a single 50‑mg oral administration of osilodrostat were cut into 2‑mm segments, extracted under standard conditions, and quantified using a fully-validate...
[Determination of 33 non-steroidal anti-inflammatory drug residues in horse urine by QuEChERS-ultra performance liquid chromatography-tandem mass spectrometry]. Non-steroidal anti-inflammatory drugs （NSAIDs） are often used to treat horses' injuries and pain due to long-term training and competitions. In equestrian competitions， NSAIDs do not affect the upper limit of a horse's athletic ability， but they can enable the horse to perform close to its maximum capacity by reducing inflammation and pain. This not only affects the competition results， but also fails to ensure the health and welfare of the horses. Therefore， it has become crucial to effectively monitor and control NSAIDs residues during equestrian competition. In this study， a r...
Equine Metabolic Syndrome and Insulin Dysregulation. Equine metabolic syndrome (EMS) is defined as a collection of metabolic and clinical features that contribute to the development of hyperinsulinemia-associated laminitis (HAL). Insulin dysregulation (ID) is the hallmark feature of EMS and a risk factor for development of HAL. There are several diagnostic tests that can be used to diagnose various forms of ID in horses and ponies. Treatment of EMS/ID includes providing an appropriate diet, exercise program, and pharmacologic intervention in some severe cases.
Effects of sympathomimetic agents on heart rate variability during general anesthesia in Thoroughbred horses. Heart rate variability (HRV) is widely used as a noninvasive index of autonomic nervous system activity. The objective of this study was to determine whether the administration of sympathomimetic agents alters HRV indices during general anesthesia in Thoroughbred horses. Five healthy Thoroughbred horses were anesthetized with sevoflurane in oxygen. During 2-5 hr of general anesthesia, five treatments were administered to each horse in a randomized order. Two doses (µg·kg·min) of epinephrine (0.1 and 0.5), norepinephrine (0.5 and 1), dobutamine (1 and 5), dopamine (5 and 15), and saline (as ...
Use of Sildenafil Citrate for the Treatment of Erectile Dysfunction in Stallions: First Case Reports. Pharmacological aids can be useful alternatives to enhance penile erection and/or improve ejaculatory function, thereby prolonging the reproductive life of stallions with ejaculatory disorders. This study aimed to evaluate the effects of sildenafil citrate in the treatment of erectile dysfunction and on semen quality in two aged stallions, a Quarter Horse (18 years) and a Mangalarga Marchador (25 years), presented to the Veterinary Hospital of FMVZ-UNESP, Botucatu, SP, Brazil. The treatment consisted of oral administration of sildenafil citrate at 0.2 mg/kg. Thirty minutes after administ...
Blood pressure, electrolyte and fluid balance in horses with insulin dysregulation after short-term treatment with canagliflozin. Short-term treatment with SGLT-2 inhibitors decreases blood pressure in people with type 2 diabetes. The aim was to investigate the impact of a 3-week treatment with canagliflozin on blood pressure in insulin dysregulated (ID) horses and to study effects on fluid balance. This was a single-centre, randomised, double-blind, placebo-controlled, parallel design study. The primary study evaluated glucose and insulin responses during an oral sugar test, and these results have been published previously. Here we report the effect of canagliflozin treatment on blood pressure, PCV, serum proteins and e...
Pituitary Pars Intermedia Dysfunction. Pituitary pars intermedia dysfunction (PPID) is one of the most common equine endocrine disorders. It is caused by oxidative damage to dopaminergic neurons in the hypothalamus and results in loss of inhibition of the pituitary pars intermedia. This leads to increased circulating concentrations of adrenocorticotropic hormone (ACTH) and related peptides. Diagnosis is based on increased resting and/or thyrotropin releasing hormone-stimulated ACTH concentrations. Assessment of insulin regulation is also important, as insulin dysregulation occurs in at least one-third of PPID cases and is associate...
Synthesis and Characterization of 2-(1-Hydroxyethyl)Promazine Sulfoxide-d4 HCl as an Internal Standard for the Accurate Quantitation of 2-(1-Hydroxyethyl)Promazine Sulfoxide in Equine Urine. Acetylpromazine, 1-{10-[3-(dimethylamino)propyl]-10H-phenothiazin-2-yl}ethenone, CHNOS, 326.46 g·mol is a phenothiazine derivative at one time used in human medicine as an antipsychotic medication but now predominantly used in veterinary medicine as a sedative/tranquilizer and referred to as acepromazine. In performance horses its use is regulated by using a 10 ng/mL threshold for the major urinary metabolite 2-(1-hydroxyethyl) promazine-sulfoxide (HEPS) in equine urine. To enable accurate quantitation of HEPS in equine urine we have synthesized and purified hydroxyethylpromazine sulfoxid...
Analgesic use, safety and pharmacokinetics of acetaminophen in equids: A structured scoping review. Despite its frequent use in equine clinical practice, scientific data on the use of acetaminophen in horses remain limited. Objective: To map and critically appraise the available evidence on the analgesic use, safety and pharmacokinetics of acetaminophen in horses. Methods: Structured scoping review. Methods: A comprehensive search was performed in accordance with the PRISMA Extension for Scoping Reviews using the terms '(paracetamol OR acetaminophen) AND (pain OR safety OR toxicosis OR pharmacokinetics) AND (horse OR pony OR donkey OR mule)' across Web of Science, Scopus, and PubMed from dat...
In Vivo Metabolite Formation and In Vitro Cytochrome P450-Mediated Metabolism of Vonoprazan in Horses. Vonoprazan is a potassium-competitive acid blocker with potential for the treatment of equine gastric ulcer syndrome. Vonoprazan metabolic pathways in horses have not been characterized. This study aimed to identify vonoprazan metabolites following oral administration and to determine the metabolic enzymes responsible for their metabolism using in vitro models. Six healthy adult Thoroughbred horses received vonoprazan (0.5 and 1 mg/kg PO) in a randomized crossover design. Plasma concentrations of vonoprazan-N-oxide (M-I) and vonoprazan-nitrone (M-III) were quantified using a validated liquid...
Epidural 0.125% ropivacaine is safe but insufficient for induced tibiotarsal joint pain. Epidural injection of a low concentration of the local anaesthetic ropivacaine produces analgesia without neurological deficits or ileus in people. Objective: To determine if epidural 0.125% ropivacaine mitigates induced hindlimb lameness in horses while preserving neurological function and gastrointestinal (GI) motility. Methods: Randomised, blinded, controlled, crossover study. Methods: Eight healthy, sound horses underwent two treatments in random order, separated by at least 3 weeks: epidural saline or epidural ropivacaine. For each treatment, an epidural catheter was inserted at the fir...
Quantifying the Equine Pain Response to Paracetamol Administration in Horses With Chronic Lameness Already Receiving Non-Steroidal Anti-Inflammatories. Paracetamol is used in horses alongside non-steroidal anti-inflammatories (NSAIDs) for multi-modal analgesia; however to date there are few studies published which have investigated its analgesic effect in the horse. Horses were recruited to this study from a population of geriatric horses at The Horse Trust. Horses were selected based on the following inclusion criteria; documented naturally occurring chronic lameness and being treated with an NSAID at the licensed dose and dosing interval. This population was assessed with a five-point subjective lameness grading system performed live by two...
Effects of omeprazole therapy administered via different routes on urinary parameters and selected interleukins in horses with equine gastric ulcer syndrome. Equine gastric ulcer syndrome (EGUS) is commonly treated with proton pump inhibitors such as omeprazole, administered orally or by injection. In humans, omeprazole has been associated with acute interstitial nephritis (AIN) and acute kidney injury (AKI), potentially linked to oxidative stress, and urinary interleukins may serve as early non-invasive markers. However, this association has not been established in horses. Objective: To evaluate the effects of oral and injectable omeprazole on basic urinary parameters and selected interleukin levels, with particular emphasis on the potential risk ...
Pharmacokinetic/Pharmacodynamic Analysis of Quinidine-Induced Dominant Frequency Reduction in Thoroughbred Horses With Atrial Fibrillation. Quinidine has long been used for the pharmacological treatment of atrial fibrillation (AF) in horses; however, the plasma concentration required for conversion to sinus rhythm remains unclear. Dominant frequency (DF), derived from surface electrocardiograms, reflects atrial activation rate during AF. This study aimed to quantify the relationship between plasma quinidine concentration and DF using a pharmacokinetic/pharmacodynamic (PK/PD) approach. Ten Thoroughbred horses with naturally occurring AF received quinidine sulfate via a nasogastric tube. Plasma quinidine concentrations and DF values...
Detection of Cyclosporine in Horse Hair After Ocular Implant Administration. This study describes the detection and temporal distribution of cyclosporine in equine hair following ocular implant administration in a Thoroughbred gelding. Mane hair samples were collected at 172- and 217-day post-implantation and analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after alkaline hydrolysis and liquid-liquid extraction. The method achieved an estimated limit of detection of 0.1 pg/mg. Cyclosporine was detected in hair at both sampling time points, with segmental analysis revealing distribution patterns consistent with systemic exposure and incorporation ...
Horses undergoing supramaximal fixed-speed treadmill exercise after administration of furosemide experience less severe acidosis and slower onset of fatigue. To document changes in acid-base and ion balance during exercise following furosemide administration and to relate them to performance. Unassigned: 6 fit Thoroughbred horses received 0.5 mg/kg IV furosemide (F) or a placebo (C) in randomized crossover order 4 hours before galloping to fatigue on a treadmill at the speed equated with an oxygen demand of 1.15 X maximum oxygen consumption (V˙o2max). Arterial and mixed venous blood was sampled before treatment, preexercise, after 2-minute warm-up, at fatigue, and 1 minute postexercise. The pH, temperature-corrected Pco2, total CO2, and sodium, po...
Detection and confirmation of hypoxia-inducible factor activating agents in equine plasma and urine by liquid chromatography coupled to mass spectrometry. Hypoxia-inducible factor (HIF) activating agents can promote the transcription of the erythropoietin gene, enhancing an athlete's performance, and are therefore prohibited in sports. A liquid chromatography coupled to high-resolution mass spectrometry (LCHRMS) method was developed for the detection and confirmation of 11 HIF-activating substances in equine plasma and urine. Ammonium formate added to the mobile phase system suppressed the responses of all the analytes in either positive or negative ion mode and thus was not used. The starting organic percentage in the mobile phase gradient and ...
The effect of fenugreek (Trigonella foenum-graecum) on stallion spermatozoa motility and vitality in vitro. This study evaluated the effects of Trigonella foenum-graecum L. (fenugreek) seed extract on stallion spermatozoa quality in vitro, focusing on motility, vitality, and functional competence. In vitro spermatozoa analyses showed that fenugreek seed extract did not demonstrate overt cytotoxicity under the tested conditions: S1 = 1562 µg/mL; S2 = 781 µg/mL; S3 = 390.5 µg/mL; S4 = 195.25 µg/mL; S5 = 97.62 µg/mL; S6 = 48.81 µg/mL; S7 = 24.40 µg/mL. Computer-assisted semen analysis (CASA) revealed a concentration- and time-dependent Treatment × Time interac...
Canagliflozin treatment of a horse with hyperinsulinemia, including pharmacokinetic analysis of different dosing protocols: a case report. Laminitis is a complex and painful disease of the equine foot. Insulin dysregulation (ID) resulting in hyperinsulinemia is responsible for more than 90% of cases in the general horse and pony population. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a relatively new class of drug that has gained considerable popularity as an off-label treatment of hyperinsulinemia-associated laminitis (HAL) in horses when traditional management changes and treatments are unsuccessful. In Canada, canagliflozin is the SGLT2i most available to equine veterinarians; although no dosing protocols have been ...
Simple and efficient HPLC-MS/MS method for simultaneous extraction and quantification of anthelmintics in equine manure. Anthelmintic treatment is a common practice in horses. The presence of pharmaceutical residues in fields and pastures is well-documented affecting various organisms, like nematodes. This study describes the development and validation of a high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method using multiple reaction monitoring (MRM) for extracting and determining the concentrations of four commonly used anthelmintics in horse manure. Manure was initially dried, then spiked with various concentrations (10-10,000 ng) of anthelmintics and extracted using an acetonit...
