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.
Bupivacaine in combination with sildenafil (Viagra) and vitamin D3 have anti-inflammatory effects in osteoarthritic chondrocytes. To treat osteoarthritic chondrocytes and thereby reduce the inflammation with a drug combination that primarily affects 5-HT- and ATP-evoked Ca2+ signaling. In osteoarthritic chondrocytes, Ca2+ signaling is elevated, resulting in increased production of ATP and inflammatory mediators. The expression of TLR4 and Na+/K+-ATPase was used to evaluate the inflammatory status of the cells. Methods: Equine chondrocytes were collected from joints with mild structural osteoarthritic changes and cultured in monolayers. The cells were treated with a combination of bupivacaine (1 pM) and sildenafil (1 ...
The equine metabolism of the catechol-O-methyltransferase enzyme inhibitor nitecapone. The abuse of performance-enhancing catecholamine-based stimulants, such as levodopa, is controlled in horse racing through the application of a regulatory threshold for the common major metabolite. However, catechol-O-methyltransferase (COMT) enzyme inhibitors can be used to restrict the catalysis of the stimulant, and so the concurrent administration of both substances would be a viable strategy to enhance racing performance while removing the risk of exceeding the threshold. A 200 mg dose of nitecapone, a COMT inhibitor, was administered to a Thoroughbred horse, and we have analysed the bl...
Pharmacokinetics of paracetamol in the Thoroughbred horse following an oral multi-dose administration. Paracetamol is a widely used, non-opioid analgesic and antipyretic drug. Scientific evidence suggests that it is an effective pain treatment in equine medicine. However, there is very little published information about the pharmacokinetics of the drug in the horse. The aim of the research was to determine the pharmacokinetics of paracetamol in equine plasma and urine to inform treatment of Thoroughbred racehorses. In this multi-dose study, paracetamol was administered orally at 20 mg/kg to six Thoroughbred horses. Pre- and post-administration urine and plasma samples were collected and analys...
Molecular Identification of Selected Tick-Borne Protozoan and Bacterial Pathogens in Thoroughbred Racehorses in Cavite, Philippines. Tick-borne diseases (TBDs) considerably impair equine health and productivity. Moreover, TBDs, particularly equine piroplasmosis, impede international movement and trade of equids, which is a vital component of the global horse racing industry. In the Philippines, horse racing is a lucrative industry generating millions of USD annually. However, information on equine TBDs is scarce. This study intended to describe molecularly the equine tick-borne infections in a racehorse park in Cavite, Philippines and identify the risk factors associated with the infections. One hundred twenty-four (n = 124...
Effect of Fentanyl Infusion on Heart Rate Variability and Anaesthetic Requirements in Isoflurane-Anaesthetized Horses. Controversy continues to surround the use of opioids in equine anaesthesia, with variable effects reported. This blinded clinical study aimed to investigate the influence of a low-dose fentanyl continuous rate infusion (CRI) on isoflurane requirements, parasympathetic tone activity (PTA), and anaesthetic parameters in horses during general anaesthesia. All of the twenty-two horses included in the research underwent a standard anaesthetic protocol. Eleven horses in the fentanyl group (Group F) received a loading dose of fentanyl at 6 µg/kg, followed by a CRI of 0.1 µg/kg/min during anaesthesi...
Kinematic Patterns in Horses Sedated With Low Doses of Detomidine: An Accelerometric Evaluation. Alpha-2-adrenergic drugs, such as detomidine, are commonly used to sedate lame horses during examination. However, the use of these drugs should be minimized, as they have numerous side-effects, like ataxia. Therefore, we wanted to test the effects, on the locomotor pattern, of low doses of detomidine (0.003 mg/kg). Six horses were sedated with 0.003 mg/kg of detomidine and compared with the same horses administered a saline solution. Using a triaxial accelerometer, data of kinetic, coordination and energetic locomotor parameters and the degree of sedation were collected. The effects were moni...
Preliminary study on the effects of pergolide on left ventricular function in the horses with pituitary pars intermedia dysfunction. Pituitary pars intermedia dysfunction (PPID), a neurodegenerative disease leading to reduced dopamine production, is a common disease in aged horses. The treatment is based on administration of the dopamine agonist pergolide. This drug has been related to valvular fibrosis in humans, but the cardiovascular effect of this drug has not yet been investigated in horses. Objective: To determine whether pergolide induces valvular disease in horses or affects the cardiac function. Methods: Standard, tissue Doppler (TDE) and two-dimensional speckle tracking (STE) echocardiography were performed in hor...
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...
Intra-articular administration of antibiotics in horses: Justifications, risks, reconsideration of use and outcomes. Antibiotics have been injected intra-articularly by equine veterinarians for decades, either prophylactically when other drugs are administered for osteoarthritis or therapeutically to treat septic arthritis. This route of administration has also more recently gained attention in human orthopaedic clinical practice, particularly as an alternative to systemic antibiotic administration to treat infections following prosthetic arthroplasty. While the rationale for injecting antibiotics intra-articularly has been largely focused on achieving high local drug concentrations, there has been relativel...
Efficacy and Side Effects of Low Single Doses of Cloprostenol Sodium or Dinoprost Tromethamine to Induce Luteolysis in Donkeys. Due to the limited literature available evaluating doses of Prostaglandin F2α in donkeys, doses for horses have been extrapolated and used as guidelines. This study aimed to assess the efficacy and side effects of four different cloprostenol sodium and dinoprost tromethamine doses to induce luteolysis in jennies. Sixty-three cycles of seven Jennies (nine cycles per jenny) were used in this study. Seven days after ovulation, jennies randomly received one of the treatments in a crossover design as follows: Control, no treatment was administered; C1, 250 µg of cloprostenol sodium (CS, Estrumate...
Sustained Intra-Articular Release and Biocompatibility of Tacrolimus (FK506) Loaded Monospheres Composed of [PDLA-PEG1000]-b-[PLLA] Multi-Block Copolymers in Healthy Horse Joints. There is an increasing interest in controlled release systems for local therapy in the treatment of human and equine joint diseases, aiming for optimal intra-articular concentrations with no systemic side effects. In this study, the intra-articular tolerability and suitability for local and sustained release of tacrolimus (FK506) from monospheres composed of [PDLA-PEG1000]-b-PLLA multiblock copolymers were investigated. Unloaded and tacrolimus-loaded (18.4 mg tacrolimus/joint) monospheres were injected into the joints of six healthy horses, with saline and hyaluronic acid (HA) in the contralat...
Synergistic combinations of clarithromycin with doxycycline or minocycline reduce the emergence of antimicrobial resistance in Rhodococcus equi. The alarming increase in rifampin and macrolide resistance among Rhodococcus equi isolates highlights the need to identify alternative therapeutic options that can effectively control rhodococcosis in foals while limiting the further development of drug resistance. Objective: To evaluate bacterial killing, antibiotic synergism and mutant prevention concentrations (MPCs) of clarithromycin alone and in combination with doxycycline, minocycline or rifampin against clinical isolates of R equi. Methods: In vitro experiments. Methods: Bacterial time-kill, fractional inhibitory concentration (checker...
Plasma and urine pharmacokinetics of hydroxyzine and cetirizine following repeated oral administrations to exercised horses. Hydroxyzine and cetirizine are first- and second-generation oral antihistamine drugs, respectively, used to treat allergic reactions in horses. Cetirizine is also a metabolite of hydroxyzine, which may lead to complexities in regulating their use in equine sporting events. The aim of the research was to be able to provide detection times (DT) from pharmacokinetic studies in thoroughbred horses to better inform trainers, and their veterinary surgeons, prescribing these substances for treatment of Thoroughbred racehorses. Six and two horses were given 9 repeated administrations of hydroxyzine HC...
In vitro and in vivo metabolism of the anabolic-androgenic steroid oxandrolone in the horse. Oxandrolone is an anabolic-androgenic steroid with favourable anabolic to androgenic ratio, making it an effective anabolic agent with less androgenic side effects. Although its metabolism has been studied in humans, its phase I and II metabolism has not been previously reported in the horse. The purpose of this study was to investigate the in vitro metabolism of oxandrolone (using both equine liver microsomes and S9) and in vivo metabolism following oral administration (three daily doses of 50 mg of oxandrolone to a single Thoroughbred horse), using both gas and liquid chromatography-mass s...
Detection and confirmation of zilpaterol in equine hair using liquid chromatography-mass spectrometry. Zilpaterol is a β -adrenergic agonist and a repartitioning agent that has a high potential for abuse in equine performance athletes. Analysis of zilpaterol in hair is an alternative sampling matrix that extends detection time periods beyond those found in urine or blood samples. Our laboratory has been screening for zilpaterol in hair for many years and recently detected and confirmed its presence in official samples. Accordingly, a liquid chromatography-mass spectrometry method was developed and validated to detect and confirm zilpaterol in equine hair. Briefly, equine hair was decontaminate...
Comparison of Recovery Quality Following Medetomidine versus Xylazine Balanced Isoflurane Anaesthesia in Horses: A Retrospective Analysis. Medetomidine partial intravenous anaesthesia (PIVA) has not been compared to xylazine PIVA regarding quality of recovery. This clinical retrospective study compared recoveries following isoflurane anaesthesia balanced with medetomidine or xylazine. The following standard protocol was used: sedation with 7 µg·kg medetomidine or 1.1 mg·kg xylazine, anaesthesia induction with ketamine/diazepam, maintenance with isoflurane and 3.5 µg·kg·h medetomidine or 0.7 mg·kg·h xylazine, and sedation after anaesthesia with 2 µg·kg medetomidine or 0.3 mg·kg xylazine. Recovery was timed and, using vi...
Species Differences in Metabolism of Soluble Epoxide Hydrolase Inhibitor, EC1728, Highlight the Importance of Clinically Relevant Screening Mechanisms in Drug Development. There are few novel therapeutic options available for companion animals, and medications rely heavily on repurposed drugs developed for other species. Considering the diversity of species and breeds in companion animal medicine, comprehensive PK exposures in the companion animal patient is often lacking. The purpose of this paper was to assess the pharmacokinetics after oral and intravenous dosing in domesticated animal species (dogs, cats, and horses) of a novel soluble epoxide hydrolase inhibitor, EC1728, being developed for the treatment of pain in animals. Results: Intravenous and oral adm...
Increase of Adverse Events After Intravenous Injection of Gentamicin in Horses Between 2015 and 2017-From Marketing Authorization Holder’s Point of View. Between 2015 and 2017, a marked increase of anaphylactic-like reactions after intravenous administration of gentamicin was observed first in horses and, later, also in humans. This worldwide issue led to safety measures including product recalls and safety warnings. Here, a German Marketing Authorization Holder (MAH) of an early and intensely affected veterinary product containing gentamicin describes the clinical approach of the company to analyze the root cause and identify the causative agent in the active pharmaceutical ingredient (API). The pharmacovigilance data of the MAH are presented,...
Gentamicin-induced sensorineural auditory loss in healthy adult horses. Irreversible sensorineural auditory loss has been reported in humans treated with aminoglycosides but not in horses. Objective: Investigate if auditory loss occurs in horses treated using the recommended IV daily dosage of gentamicin for 7 consecutive days. Methods: Ten healthy adult horses (7-15 years; females and males, 5 each). Methods: Prospective study. Physical and neurological examinations and renal function tests were performed. Gentamicin sulfate was administered at a dosage of 6.6 mg/kg via the jugular vein on alternating sides for 7 days. Gentamicin peak and trough concentratio...
Constitutive and differential expression of transport protein genes in Parascaris univalens larvae and adult tissues after in vitro exposure to anthelmintic drugs. The equine roundworm Parascaris univalens has developed resistance to the three anthelmintic substances most commonly used in horses. The mechanisms responsible for resistance are believed to be multi-genic, and transport proteins such as the P-glycoprotein (Pgp) family have been suggested to be involved in resistance in several parasites including P. univlaens. To facilitate further research into the mechanisms behind drug metabolism and resistance development in P. univalens we aimed to develop an in vitro model based on larvae. We developed a fast and easy protocol for hatching P. univalens...
Evaluation of corneal anaesthesia after the application of topical 0.5% bupivacaine, 2% lidocaine and 0.4% oxybuprocaine in normal horses. To compare the corneal anaesthetic effect of 0.5% bupivacaine, 2% lidocaine and 0.4% oxybuprocaine on normal equine eyes. Methods: Prospective, blinded crossover study. Methods: A group of 10 clinically healthy horses. Methods: Corneal sensitivity was determined in each eye by measuring corneal touch threshold (CTT). The study had three phases. Each subject was randomly given one of the three treatments followed by a 72 hour washout period. Every horse received all treatments. Baseline CTT was recorded prior to anaesthetic instillation (T0) then CTT was measured 5 and 10 minutes after (T1 and ...
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 ...
Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing Horses. The aim of this study was to investigate the safety and pharmacokinetics of trimethoprim-sulphadiazine administered via intravenous regional limb perfusion (IVRLP) into the cephalic vein. According to the hypothesis, the drug could be administered without adverse effects and the synovial concentrations would remain above the minimum inhibitory concentration (MIC) for trimethoprim-sulphadiazine (0.5 and 9.5 µg/mL) for 24 h. Ten ( = 10) horses underwent cephalic vein IVRLP with an Esmarch tourniquet applied for 30 min. Four grams (4 g) of trimethoprim-sulphadiazine (TMP-SDZ) were diluted at 0.9...
Cardiorespiratory, Sedative and Antinociceptive Effects of a Medetomidine Constant Rate Infusion with Morphine, Ketamine or Both. Standing surgery under sedation reduces anesthetic-related mortality in horses. Medetomidine, alone and combined with morphine in a constant rate infusion (CRI), has been described for standing surgery but their cardiorespiratory, sedative and antinociceptive effects have never been compared. The addition of ketamine could improve analgesia in these procedures with minimal cardiorespiratory consequences. The objectives were to compare the cardiorespiratory effects, quality of sedation, antinociception and ataxia produced by administration of a medetomidine-based CRI with morphine, ketamine or ...
Nonlinear Mixed-Effect Pharmacokinetic Modeling and Distribution of Doxycycline in Healthy Female Donkeys after Multiple Intragastric Dosing-Preliminary Investigation. Doxycycline (DXC) is a broad-spectrum antibacterial antimicrobial administered to horses for the treatment of bacterial infections which may also affect donkeys. Donkeys have a different metabolism than horses, leading to differences in the pharmacokinetics of drugs compared to horses. This study aimed to describe the population pharmacokinetics of DXC in donkeys. Five doses of DXC hyclate (10 mg/kg) were administered via a nasogastric tube, q12 h, to eight non-fasted, healthy, adult jennies. Serum, urine, synovial fluid and endometrium were collected for 72 h following the first administratio...
The Rho kinase (ROCK) inhibitor Y-27632 reduces the β2-adrenoceptor density but enhance cAMP formation in primary equine bronchial epithelial cells. The present study addresses the effect of the Rho-kinase (ROCK) inhibitor Y-27632 on the β-adrenoceptor density and β-agonist-stimulated intracellular second messenger cAMP formation in primary equine bronchial epithelial cells (EBEC). Y-27632 significantly decreased the β-adrenoceptor number (B) without markedly affecting the receptor affinity (dissociation constant, K) to the radioligand [I]-iodocyanopindolol (ICYP). In contrast, Y-27632 augmented the β-agonist-stimulated intracellular cAMP production. Herein, Y-27632 markedly increased the maximal cAMP responses (E) (isoproterenol >...
Pharmacokinetics of dipyrone in horses: A multi-dose, dose escalation study. Dipyrone is a non-opioid, nonsteroidal anti-inflammatory drug with antipyretic and analgesic properties commonly used in horses. Dipyrone is rapidly hydrolyzed to the primary active metabolite 4-methylaminoantipyrine (4-MAA). The purpose of this study was to determine the pharmacokinetic profile of 4-MAA following repeated and escalating doses of intravenously administered dipyrone. Twenty-six horses were randomly allocated to five treatment groups (one placebo group and four dipyrone groups [30 mg/kg q8h, 30 mg/kg q12h, 60 mg/kg q8h, and 90 mg/kg q12h]) and treated for nine consecutive da...
Ivermectin treatment in lactating mares results in suboptimal ivermectin exposure in their suckling foals. The management of equine strongyles has become problematic over the last decade because of an increased prevalence of drug-resistant isolates worldwide. Therapeutic options are therefore limited, leaving macrocyclic lactones as the most often effective drug class. However, their lipophilic properties result in a long-lasting elimination that could favour drug resistance selection. As a result, ivermectin treatment in lactating mares could promote suboptimal exposure of their foal parasites to ivermectin, thereby selecting for more resistant worms. To test for this putative transfer, we selecte...
Accelerometric Evaluation of the Locomotor Pattern After Administration of Morphine in Conscious Healthy Horses. The objective of the present study was to compare, using accelerometry, the gait changes produced after administration of a dose of 0.2 mg/kg of morphine at the walk in healthy horses. Six mature horses were used, and all animals received two different treatments with, at least, two weeks interval in between. Treatments administered consisted of a single dose of 10 ml of saline solution or a total of 0.2 mg/kg of morphine diluted in 10 ml of saline solution. A three-dimensional accelerometric device was used to collect data continuously while horses were walking. The walking test was performed...
Evaluation of intramuscular anesthetic protocols in healthy domestic horses. To assess anesthetic induction, recovery quality and cardiopulmonary variables after intramuscular (IM) injection of three drug combinations for immobilization of horses. Methods: Randomized, blinded, three-way crossover prospective design. Methods: A total of eight healthy adult horses weighing 470-575 kg. Methods: Horses were administered three treatments IM separated by ≥1 week. Combinations were tiletamine-zolazepam (1.2 mg kg), ketamine (1 mg kg) and detomidine (0.04 mg kg) (treatment TKD); ketamine (3 mg kg) and detomidine (0.04 mg kg) (treatment KD); and tiletamine-zolazepam (2.4 mg ...