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.
Long-term monitoring of clodronate in equine hair using liquid chromatography-tandem mass spectrometry. Given the potential for long-term inhibition of bone remodeling/healing and detrimental effects to horses in training, bisphosphonates are tightly regulated in horseracing. Hair has proven to be an effective matrix for detection of drug administration to horses and has been particularly effective in detecting drugs for a long period of time post administration. Thus, hair may prove to be a useful matrix for detection of administration of this class of drugs. The objective of the current study was to develop an assay and assess the usefulness of hair as a matrix for long-term detection of clodr...
A randomized, triple-blinded controlled clinical study with a novel disease-modifying drug combination in equine lameness-associated osteoarthritis. This study aimed to test a novel treatment combination (TC) (equivalent to sildenafil, mepivacaine, and glucose) with disease-modifying properties compared to Celestone® bifas® (CB) in a randomized triple-blinded phase III clinical study in horses with mild osteoarthritis (OA). Joint biomarkers (reflecting the articular cartilage and subchondral bone remodelling) and clinical lameness were used as readouts to evaluate the treatment efficacy. Unassigned: Twenty horses with OA-associated lameness in the carpal joint were included in the study and received either TC (n = 10) or CB (n = ...
Pharmacokinetics, clinical efficacy and safety of acetaminophen (paracetamol) in adult horses with naturally occurring chronic lameness. Acetaminophen is used clinically in horses with musculoskeletal pain; however, no studies have been performed in horses with chronic lameness. Objective: To determine the pharmacokinetics, safety and efficacy of chronic dosing of acetaminophen in horses with naturally occurring chronic lameness. Methods: Longitudinal. Methods: Twelve adult horses with chronic lameness were treated with acetaminophen (30 mg/kg PO) every 12 h for 21 days. Plasma concentrations of acetaminophen were analysed on days 7 and 21 via LC-MS/MS and noncompartmental pharmacokinetic analysis. Lameness was evaluated ...
Effects of a 10% dimethyl sulfoxide solution on radiocarpal joint amikacin pharmacokinetics during intravenous regional limb perfusion in standing sedated horses. To determine the effect of a 10% dimethyl sulfoxide (DMSO) solution on the peak concentration (C ) of amikacin in the radiocarpal joint (RCJ) during intravenous regional limb perfusion (IVRLP) compared with 0.9% NaCl. Methods: Randomized crossover study. Methods: Seven healthy adult horses. Methods: The horses underwent IVRLP with 2 g of amikacin sulfate diluted to 60 mL using a 10% DMSO or 0.9% NaCl solution. Synovial fluid was collected from the RCJ at 5, 10, 15, 20, 25, and 30 minutes after IVRLP. The wide rubber tourniquet placed on the antebrachium was removed after the 30 min sample. A...
Detection of boldenone in the urine of female horses-ex vivo formation versus administration. Boldenone is an anabolic-androgenic steroid (AAS) that is prohibited in equine sports. However, in certain situations, it is endogenous, potentially formed by the microbes in urine. An approach to the differentiation based on the detection of the biomarkers Δ1-progesterone, 20(S)-hydroxy-Δ1-progesterone and 20(S)-hydroxyprogesterone was assessed, and their concentrations were monitored in the urine of untreated female horses (n = 291) alongside boldenone, boldienone, testosterone and androstenedione. Using an ultra-sensitive analytical method, boldenone (256 ± 236 pg/mL, n = 2...
Novel holistic pharmacokinetic model applied to plasma and urine concentrations of 2,5-dihydroxybenzene sulphonate following administrations of calcium dobesilate and etamsylate to exercised horses. Calcium dobesilate (CD) is a synthetic venoactive drug used in veterinary medicine to treat equine navicular disease. Etamsylate is a haemostatic agent used in horses for the treatment of exercise-induced pulmonary haemorrhage. Both etamsylate and CD dissociate in the circulatory system with 2,5-HBSA as the active drug. The aim of the research was to be able to provide detection time (DT) advice from pharmacokinetic (PK) studies in Thoroughbred horses to better inform trainers, and their veterinary surgeons, prescribing these substances for treatment of Thoroughbred racehorses. Two (pilot stud...
Identification of erythropoietin mimetic peptide 1 linear form in a sealed vial and its administration study in horses for doping control purpose. The erythropoietin mimetic peptide 1 linear form (EMP1-linear), GGTYSCHFGPLTWVCKPQGG-NH , was identified in an unknown preparation consisting of white crystalline powder contained in sealed glass vials using ultrahigh performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). The white crystalline powder, allegedly used for doping racehorses, was found to contain around 2% (w/w) of EMP1-linear. EMP1-linear can be cyclised in equine plasma at physiological temperature of 37°C by forming an intramolecular disulfide bond to give EMP1, which is a well-known erythropoiesis st...
[New drugs for horses and food-producing animals in 2022]. In 2022, one novel pharmaceutical agent was released on the German market for horses or food-producing animals: An injection suspension for horses containing tenogenic primed equine allogeneic peripheral blood-derived mesenchymal stem cells as the active ingredient (RenuTend®) is now available. The authorization of one established veterinary active ingredient was extended to an additional species: The synthetic prostaglandin F2α-analogue cloprostenol (Syncroprost®) received approval for goats. Additionally, for 2 active ingredients (paracetamol, suxibuzone), drugs with a higher content of t...
Equine in vivo metabolite profiling of the selective androgen receptor modulator LGD-3303 for doping control. LGD-3303 is a Selective Androgen Receptor Modulator (SARM) that is prohibited in both equine and human sports due to its anabolic properties. The aim of this study was to investigate the equine in vivo metabolite profile of LGD-3303 and identify drug metabolites that can be suitable as new and improved analytical targets for equine doping control. This was performed by an oral administration of 0.05 mg·kg LGD-3303 to horses, where blood and urine samples were collected up to 96 h after administration. The in vivo samples consisting of plasma, urine and hydrolyzed urine were analyzed utilizi...
Detection of gonadotropin-releasing hormone and its analogues in equine and canine urine by high-resolution data-independent acquisition. Gonadotropin-releasing hormone (GnRH) and its synthetic analogues are considered banned substances by the racing industry. GnRH is used as a pharmaceutical to regulate the female oestrous cycle, but the hormone is also thought to increase the production of testosterone in male animals. Using liquid chromatography in conjunction with high-resolution mass spectrometry (LC-HRMS) and data-independent acquisition (DIA), a method is presented for the detection of intact and truncated peptides of GnRH and its analogues down to the low picogram level in equine urine. The study of the catabolism of GnR...
Electrospray ionization mass spectrometry adduct formation by mobile phase additives: A case study using nitrile functional groups containing selective androgen receptor modulators. The formation of mass adducts is common during electrospray ionization mass spectrometry (ESI-MS). However, the mechanism that leads to adduct formation is poorly understood and difficult to control. Multiplication of mass adducts at once will adversely impact the sensitivity of mass analysis and cause misinterpretation of the level of detection. Prior studies on selective androgen receptor modulators (SARMs) revealed an immense mass adduct formation in both positive and negative ESI modes. Methods: In this study, additives in the mobile phases are investigated as a potential means of controll...
Review of the Mechanism of Action and Use of Bisphosphonates in Horses. Bisphosphonates are a group of drugs that can reduce bone resorption by incorporating into the crystal structure of exposed hydroxyapatite where they are taken up by osteoclasts. Bisphosphonates have several other mechanisms of action including reducing pain and inflammation and altering macrophage function. There are two types of bisphosphonates-nitrogenous and non-nitrogenous, the latter of which is used in horses. This article provides a literature-based review of the proposed mechanisms of action and therapeutic uses of bisphosphonates including a brief review of bone response to disease. ...
Transdermal drug delivery in horses: An in vitro comparison of skin structure and permeation of two model drugs at various anatomical sites. Oral and parenteral drug delivery in horses can be difficult. Equine-specific transdermal drug formulations offer improved ease of treatment; development of such formulations requires a deeper understanding of the structural and chemical tissue barrier of horse skin. Objective: To compare the structural composition and barrier properties of equine skin. Methods: Six warmblood horses (two males, four females) with no skin diseases. Methods: Routine histological and microscopic analyses were carried out with image analysis for skin from six different anatomical locations. In vitro drug permeatio...
Evidence and Molecular Characterization of Multidrug Resistant Staphylococcus aureus Isolated From Equines in Pakistan. The purpose of the current study was to investigate the nasal colonization and drug resistance profile of Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and vancomycin-resistant S. aureus (VRSA) in donkeys (n =63), mules (n = 42), and horses (n = 98). MRSA and VRSA were confirmed based on phenotypic and molecular methods, followed by phylogenetic analysis. Furthermore, the association of various animal and management-based risk factors with S. aureus colonization was also evaluated. The presence of nuc gene on polymerase chain reaction showed an overall prevalence of 42.86%...
Performance assessment of an equine metabolomics model for screening a range of anabolic agents. Despite their ban, Anabolic Androgenic Steroids (AAS) are considered as the most important threat for equine doping purposes. In the context of controlling such practices in horse racing, metabolomics has emerged as a promising alternative strategy to study the effect of a substance on metabolism and to discover new relevant biomarkers of effect. Based on the monitoring of 4 metabolomics derived candidate biomarkers in urine, a prediction model to screen for testosterone esters abuse was previously developed. The present work focuses on assessing the robustness of the associated method and def...
Pharmacokinetics and effects of codeine in combination with acetaminophen on thermal nociception in horses. Codeine and acetaminophen in combination have proven to be an effective analgesic treatment for moderate-to-severe and postoperative pain in humans. Studies have demonstrated that codeine and acetaminophen, when administered as sole agents, are well tolerated by horses. In the current study, we hypothesized that administration of the combination of codeine and acetaminophen would result in a significant thermal antinociceptive effect compared with administration of either alone. Six horses were administered oral doses of codeine (1.2 mg/kg), acetaminophen (20 mg/kg), and codeine plus aceta...
Pharmacokinetics of aminocaproic acid in thoroughbred horses. The antifibrinolytic agent aminocaproic acid (ACA) is occasionally used prior to episodes of intense training in racehorses suffering from exercise-induced pulmonary hemorrhage. Although a previous study indicated that the drug is cleared rapidly in horses, some racetrack practitioners claim that recent adverse analytical findings for ACA in postrace samples were from ACA administrations 5-7 days before the race. The purpose of this study was to re-examine the pharmacokinetics of ACA in horses to address this apparent conundrum. Eight exercise-conditioned thoroughbred horses were administere...
Five- versus seven-day dosing intervals of extended-release injectable omeprazole in the treatment of equine squamous and glandular gastric disease. An extended-release injectable omeprazole formulation (ERIO) has become a popular treatment for equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD) where it is available; however, published data are limited and optimal treatment regimens have not been determined. Objective: To compare effects of treatment on ESGD and EGGD when an ERIO formulation is administered at either 5- or 7-day intervals. Methods: Retrospective clinical study. Methods: Case records and gastroscopy images of horses with ESGD or EGGD treated with ERIO were reviewed. Images were anonymised and...
Control of a sulfadoxine/trimethoprim combination in the competition horse: Elimination, metabolism and detection following an intravenous administration. The combination of sulfadoxine (SDO) with trimethoprim (TMP) is widely used in veterinarian medicine. The aim of the present study was to compare excretion profiles and detection time windows of SDO and TMP in plasma and urine by means of a validated quantitative method. Eight horses received a single intravenous (i.v.) dose of 2.7 mg TMP and 13.4 mg SDO per kg bodyweight. Plasma and urine samples were collected up to 15 and 70 days post-administration, respectively. While urine samples underwent an enzymatic hydrolysis, plasma samples were proteolysed before further analysis. After solid-...
PLDLA/TPU Matrix Enriched with Cyclosporine A as a Therapeutic Platform for Immune-Mediated Keratitis (IMMK) in Horses. The purpose of this study was to describe the use of PLDLA/TPU matrix enriched with cyclosporine A (CsA) as a therapeutic platform in horses with immune-mediated keratitis (IMMK) with an in vitro evaluation CsA release and degradation of the blend as well as determination of the safety and efficacy of that platform used in the animal model. The kinetics of the CsA release from matrices constructed of thermoplastic polyurethane (TPU) polymer and a copolymer of L-lactide with DL-lactide (PLDLA) (80:20) in the TPU (10%) and a PLDL (90%) polymer blend were studied. Moreover, we used the STF (Simul...
Factors affecting untargeted detection of doping agents in biological samples. Doping control is essential for sports, and untargeted detection of doping agents (UDDA) is the holy grail for anti-doping strategies. The present study examined major factors impacting UDDA with metabolomic data processing, including the use of blank samples, signal-to-noise ratio thresholds, and the minimum chromatographic peak intensity. Contrary to data processing in metabolomics studies, both blank sample use (either blank solvent or plasma) and marking of background compounds were found to be unnecessary for UDDA in biological samples, the first such report to the authors' knowledge. The...
3-Methoxytyrosine as an indicator of dopaminergic manipulation in equine plasma. The use of catechol-O-methyltransferase inhibitors may mask doping agents, primarily levodopa, administered to racehorses and prolong the stimulating effects of dopaminergic compounds such as dopamine. It is known that 3-methoxytyramine is a metabolite of dopamine and 3-methoxytyrosine is a metabolite of levodopa thus these compounds are proposed to be potential biomarkers of interest. Previous research established a urinary threshold of 4,000 ng/mL for 3-methoxytyramine to monitor misuse of dopaminergic agents. However, there is no equivalent biomarker in plasma. To address this deficiency a...
Nanoformulation of a Trypanocidal Drug Isometamidium Chloride Ameliorates the Apurinic-Apyrimidinic DNA Sites/Genotoxic Effects in Horse Blood Cells. Isometamidium chloride (ISM) is a trypanocide for the prophylactic and therapeutic use against vector-borne animal trypanosomosis (mainly Surra caused by ) and African animal trypanosomosis caused by //). ISM was found to be an efficient trypanocide for therapeutic/prophylactic use against trypanosomosis; however, it produces some local and systemic detrimental effects in animals. We synthesized isometamidium chloride-loaded alginate gum acacia nanoformulation (ISM SANPS) to lessen the detrimental side effects of isometamidium chloride (ISM) while treating trypanosomal diseases. We intended to...
Pharmacokinetics of intra-articular buprenorphine in horses with lipopolysaccharide-induced synovitis. The objective of this study was to describe the pharmacokinetics of intra-articular (IA) administered buprenorphine in horses with lipopolysaccharide (LPS)-induced synovitis. Radiocarpal synovitis was induced in six healthy adult horses with the IA injection of LPS (0.5 ng/joint) on two occasions in a randomized cross-over design. Treatments (IA buprenorphine (IAB) at 5 μg/kg plus intravenous saline; and intravenous buprenorphine (IVB) at 5 μg/kg plus IA saline) were administered 4 h following LPS injection. Concentrations of buprenorphine were assessed in plasma and synovial fluid (SF) ...
Investigation of in vitro generated metabolites of GLPG0492 using equine liver microsomes for doping control. An effective alternative to testosterone therapy is selective androgen receptor modulators, a class of compounds that has a tissue-specific effect on muscle and bone. These drugs, which enhance performance, pose a severe abuse risk in competitive sports. GLPG0492 is one of the selective androgen receptor modulators discovered in recent decades. This compound has a unique tissue-specific action for muscle and bone against steroid receptors and acts as a partial agonist for androgen receptors. This study examined GLPG0492 and its metabolites in vitro using equine liver microsomes. Liquid chromat...
Ceftiofur use and antimicrobial stewardship in the horse. Equine practitioners require recommendations that support antimicrobial stewardship and avoid generating resistance to medically important antibiotics. This review examines current inadequacies in antimicrobial stewardship standards within the veterinary community, related to antimicrobial categorisation and prescribing practices. Resistance to cephalosporin antibiotics in horses is also described. Properties of cephalosporin antibiotics are outlined and equine-specific studies of ceftiofur, a third-generation cephalosporin antibiotic with medical importance, are detailed. Readers are provided...
Use of Liquid Chromatography–Tandem Mass Spectrometry to Quantify and Confirm the Fentanyl Metabolite N-[1-(2-Phenethy-4-Piperidinyl)] Maloanilinic Acid in Equine Urine for Doping Control. Fentanyl, a powerful synthetic mu opioid receptor agonist, is banned in equine sports by the Association of Racing Commissioners International and the Fédération Équestre Internationale. The presence of fentanyl in equine blood has been confirmed during routine post-race screening for doping substances in the authors' laboratory. While fentanyl can be detected and confirmed in blood, it is rapidly metabolized, and screening for the metabolite N-[1-(2-phenethy-4-piperidinyl)] maloanilinic acid (PMA) in equine urine is expected to allow for a longer detection time. In this study, a quantitati...
Inhibition of Myeloperoxidase Pro-Fibrotic Effect by Noscapine in Equine Endometrium. Myeloperoxidase is an enzyme released by neutrophils when neutrophil extracellular traps (NETs) are formed. Besides myeloperoxidase activity against pathogens, it was also linked to many diseases, including inflammatory and fibrotic ones. Endometrosis is a fibrotic disease of the mare endometrium, with a large impact on their fertility, where myeloperoxidase was shown to induce fibrosis. Noscapine is an alkaloid with a low toxicity, that has been studied as an anti-cancer drug, and more recently as an anti-fibrotic molecule. This work aims to evaluate noscapine inhibition of collagen type 1 (C...
Equine abortion and stillbirth in California: a review of 1,774 cases received at a diagnostic laboratory, 1990-2022. Reproductive failure represents an important cause of economic loss for the equine industry. We reviewed the cases of equine abortion and stillbirth submitted to the California Animal Health and Food Safety Laboratory System, University of California-Davis from 1990 to 2022. A total of 1,774 cases were reviewed. A confirmed cause of abortion was determined in 29.2% of the cases. Abortion or stillbirth was attributed to infectious agents in 18.7% of the cases, with Streptococcus spp., equine herpesvirus 1, and Leptospira spp. being the most prevalent. Noninfectious causes of abortion were estab...
Buprenorphine has a concentration-dependent cytotoxic effect on equine chondrocytes in vitro. To investigate the cytotoxic effects of 2 different concentrations of buprenorphine and compare them with bupivacaine and morphine on healthy equine chondrocytes in vitro. Methods: Primary cultured equine articular chondrocytes from 3 healthy adult horses. Methods: Chondrocytes were exposed for 0 and 2 hours to the following treatments: media (CON; negative control); bupivacaine at 2.2 mg/mL (BUPI; positive control); morphine at 2.85 mg/mL (MOR); buprenorphine at 0.12 mg/mL (HBUPRE); or buprenorphine at 0.05 mg/mL (LBUPRE). Chondrocyte viability was assessed using live/dead staining, water-sol...