Pharmacodynamics in horses refers to the study of how drugs affect the equine body, encompassing the mechanisms of action, the relationship between drug concentration and effect, and the duration of these effects. This field examines how drugs interact with biological systems in horses to produce therapeutic or adverse effects. Key aspects include receptor binding, post-receptor effects, and chemical interactions. Understanding pharmacodynamics is essential for determining appropriate dosages, predicting drug interactions, and assessing therapeutic outcomes in equine medicine. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacodynamic properties of various drugs in horses, focusing on their effects, efficacy, and safety profiles.
Medina-Torres CE, Underwood C, Pollitt CC, Castro-Olivera EM, Hodson MP, Richardson DW, van Eps AW.A suitable method for evaluating lamellar perfusion changes and their metabolic consequences is currently lacking. Objective: To examine perfusion changes in lamellar tissue using serial microdialysis measurements of urea clearance and energy metabolites. Methods: Randomised, controlled (within subject) experimental trial. Methods: Nine Standardbred horses were instrumented with microdialysis probes in the foot lamellar tissue and skin (over the tail base). Urea (20 mmol/l) was added to the perfusate and its clearance was used to estimate local perfusion. Samples were collected every 15 min fo...
Serrano-Rodríguez JM, Gómez-Díez M, Esgueva M, Castejón-Riber C, Mena-Bravo A, Priego-Capote F, Serrano Caballero JM, Muñoz A.The pharmacokinetics and pharmacodynamics (PK/PD) of the angiotensin-converting enzyme inhibitor (ACEI) ramiprilat after intravenous (IV) and oral (PO) administration of ramipril have not been evaluated in horses. This study was designed to establish PK profiles for ramipril and ramiprilat as well as to determine the effects of ramiprilat on serum angiotensin converting enzyme (ACE) and to select the most appropriate ramipril dose that suppresses ACE activity. Six healthy horses in a cross-over design received IV ramipril 0.050 mg/kg, PO at a dose of 0 (placebo), and 0.050, 0.10, 0.20, 0.40 ...
Sole A, Nieto JE, Aristizabal FA, Snyder JR.Emptying the vasculature with an Esmarch bandage before i.v. regional anaesthesia is commonly performed in human patients to prevent leakage of the solution under the tourniquet but there is no evidence for its efficacy in horses for antimicrobial i.v. regional limb perfusion (IV-RLP). Objective: To determine the effect on synovial fluid concentration of amikacin of emptying the vasculature before performing IV-RLP. Methods: Crossover experiment. Methods: Eight clinically healthy horses underwent 2 IV-RLP with amikacin in a randomised, crossover design. Horses received an IV-RLP with amikacin ...
Broux B, De Clercq D, Decloedt A, De Baere S, Devreese M, Van Der Vekens N, Ven S, Croubels S, van Loon G.Arrhythmias are common in horses. Some, such as frequent atrial or ventricular premature beats, may require long-term anti-arrhythmic therapy. In humans and small animals, sotalol hydrochloride (STL) is often used for chronic oral anti-arrhythmic therapy. STL prolongs repolarization and the effective refractory period in all cardiac tissues. No information on STL pharmacokinetics or pharmacodynamics in horses is available and the aim of this study was to evaluate the pharmacokinetics of intravenously (IV) and orally (PO) administered STL and the effects on surface electrocardiogram and left ve...
Bauquier JR, Boston RC, Sweeney RW, Wilkins PA, Nolen-Walston RD.Gentamicin is an aminoglycoside antimicrobial commonly used in horses at 6.6 mg/kg IV once daily. Therapeutic drug monitoring (TDM) can confirm desired peak concentration is reached for common bacterial isolates, and detect toxicosis associated with high trough values. Objective: Determine the relationship between gentamicin dose and plasma concentration in hospitalized horses, and identify a starting dose range to achieve peaks > 32 μg/mL. Methods: Sixty-five horses (2002-2010) receiving once-daily gentamicin with TDM performed (N = 99 sets). Methods: Retrospective study. Data from hospit...
Pedersen PJ, Thomsen KB, Olander ER, Hauser F, Tejada Mde L, Poulsen KL, Grubb S, Buhl R, Calloe K, Klaerke DA.The KCNH2 and KCNE2 genes encode the cardiac voltage-gated K+ channel KV11.1 and its auxiliary β subunit KCNE2. KV11.1 is critical for repolarization of the cardiac action potential. In humans, mutations or drug therapy affecting the KV11.1 channel are associated with prolongation of the QT intervals on the ECG and increased risk of ventricular tachyarrhythmia and sudden cardiac death--conditions known as congenital or acquired Long QT syndrome (LQTS), respectively. In horses, sudden, unexplained deaths are a well-known problem. We sequenced the cDNA of the KCNH2 and KCNE2 genes using RACE an...
General anaesthesia in horses is associated with elevated mortality rate in subjects suffering of heaves. Target-controlled infusion (TCI) of sedative-hypnotic medications and opioids represents a total intravenous anaesthesia (TIVA) method validated in veterinary medicine. Since there are no data concerning the impact of these classes of drugs in inducing bronchial hyperresponsiveness (BHR) in horses, the aim of this study was to investigate the effect propofol and remifentanil on the contractile response of equine airway smooth muscle. The influence of propofol and remifentanil on the contra...
Oyarzun-Ampuero F, Vidal A, Concha M, Morales J, Orellana S, Moreno-Villoslada I.The treatment of skin wounds represents an important research area due to the important physiological and aesthetic role of this tissue. During the last years, nanoparticles have emerged as important platforms to treat skin wounds. Silver, gold, and copper nanoparticles, as well as titanium and zinc oxide nanoparticles, have shown potential therapeutic effects on wound healing. Due to their specific characteristics, nanoparticles such as nanocapsules, polymersomes, solid lipid nanoparticles, and polymeric nanocomplexes are ideal vehicles to improve the effect of drugs (antibiotics, growth fact...
Giorgi M, De Vito V, Poapolathep A, Rychshanova R, Sgorbini M, Owen H.Flupirtine (FLU) is a non-opioid analgesic drug, with no antipyretic or anti-inflammatory effects, used in the treatment of a wide range of pain states in human beings. It does not induce the side effects associated with the classical drugs used as pain relievers. The aim of this study was to evaluate the pharmacokinetic profiles of FLU after IV and PO administration in healthy horses. Six mixed breed adult mares were randomly assigned to two treatment groups using an open, single-dose, two-treatment, two-phase, paired, cross-over design (2 × 2 Latin-square). Group 1 (n = 3) received ...
Vandeweerd JM, Zhao Y, Nisolle JF, Zhang W, Zhihong L, Clegg P, Gustin P.Intra-articular (IA) corticosteroids (CS) have been used in the treatment of osteoarthritis for many years, although their effects on articular cartilage are not fully understood. To identify whether previous animal studies have provided enough evidence about the effects of CS, we undertook a systematic review that identified 35 relevant in vivo animal experimental studies between 1965 and 2014 assessing the effects of CS on either normal cartilage, or in either induced osteoarthritis (OA) or synovitis. The quality of the methodology was assessed. Deleterious effects, both structural and bioc...
Derochette S, Serteyn D, Mouithys-Mickalad A, Ceusters J, Deby-Dupont G, Neven P, Franck T.Excessive neutrophil stimulation and reactive oxygen species (ROS) production are involved in numerous human or horse pathologies. The modulation of the neutrophil NADPH oxidase (NOX) has a great therapeutic potential since this enzyme produces superoxide anion whose most of the other ROS derive. The measurement of NOX activity by cell-free systems is often used to test potential inhibitors of the enzyme. A major drawback of this technique is the possible interferences between inhibitors and the probe, ferricytochrome c, used to measure the activity. We designed the "EquiNox2", a new pharmacol...
Hunter BG, Parker JE, Wehrman R, Stang B, Cebra CK.To determine synovial concentrations of morphine after intravenous regional limb perfusion (IVRLP) with morphine or morphine in combination with gentamicin in clinically healthy, standing sedated horses. Methods: Experimental. Methods: Adult horses (n = 6). Methods: IVRLP was performed using 0.1 mg/kg morphine (M) in standing sedated horses. After a 3-week washout period, IVRLP was performed on the same forelimb with a combination of 0.1 mg/kg morphine and 1 g gentamicin (M/G). Synovial fluid from the middle carpal joint of the perfused limb and jugular blood samples were collected i...
McArthur CL, Handel IG, Robinson A, Hodgkinson JE, Bronsvoort BM, Burden F, Kaplan RM, Matthews JB.Cyathostomins are the most prevalent parasitic pathogens of equids worldwide. These nematodes have been controlled using broad-spectrum anthelmintics; however, cyathostomin resistance to each anthelmintic class has been reported and populations insensitive to more than one class are relatively commonplace. The faecal egg count reduction test (FECRT) is considered the most suitable method for screening anthelmintic sensitivity in horses, but is subject to variation and is relatively time-consuming to perform. Here, we describe a larval migration inhibition test (LMIT) to assess ivermectin (IVM)...
Kutter AP, Bettschart-Wolfensberger R, Schwarzwald CC, Portier KG, Ringer SK.To evaluate the non-calibrated, minimally invasive cardiac output (CO) monitor FloTrac/Vigileo (FloTrac) against thermodilution (TD) CO in standing horses. Methods: Prospective, experimental trial. Methods: Nine adult horses weighing a median (range) of 535 (470-602) kg. Methods: Catheters were placed in the right atrium, pulmonary artery and carotid artery under local anaesthesia. CO was measured 147 times by TD and FloTrac and indexed to body weight. Changes in CO were achieved with romifidine or xylazine and dobutamine constant rate infusions. Bland-Altman analysis, concordance and polar pl...
Garrison KL, Sahin S, Benet LZ.This study was conducted to determine the number of drugs exhibiting flip-flop pharmacokinetics following oral (p.o.) dosing from immediate-release dosage forms and if they exhibit a common characteristic that may be predicted based on BDDCS classification. The literature was searched for drugs displaying flip-flop kinetics (i.e., absorption half-life larger than elimination half-life) in mammals in PubMed, via internet search engines and reviewing drug pharmacokinetic data. Twenty two drugs were identified as displaying flip-flop kinetics in humans (13 drugs), rat (nine drugs), monkey (three ...
Jordana M, Martens A, Duchateau L, Haspeslagh M, Vanderperren K, Oosterlinck M, Pille F.Controversy exists about the specificity of diagnostic analgesia of the digital flexor tendon sheath (DFTS) in horses. Objective: To evaluate the degree of diffusion of mepivacaine from the equine DFTS to adjacent synovial structures. Methods: Crossover experiment. Methods: Under general anaesthesia, the DFTS of one front and one hindlimb of 8 horses were injected simultaneously with mepivacaine. Synovial fluid samples of the injected DFTS, the adjacent metacarpo-/metatarsophalangeal (MCP/MTP) joint, proximal interphalangeal joint, distal interphalangeal joint, navicular bursa and contralatera...
Guedes A, Knych H, Hood D.Laminitis is a painful disease for which adequate pain management remains a challenging and largely unmet medical need. Objective: To investigate plasma concentrations, analgesic and physiological effects of 2 doses of tramadol in horses with chronic laminitis. Methods: Nonrandomised trial. Methods: Four horses with naturally occurring chronic laminitis received 5 mg/kg bwt and then 10 mg/kg bwt tramadol orally every 12 h for one week with a one-week washout between. Noninvasive arterial blood pressure, heart and respiratory rates, intestinal sounds and forelimb off-loading frequency were ...
Janssen IJ, Krücken J, Demeler J, von Samson-Himmelstjerna G.P-glycoproteins (Pgps) are suspected to mediate drug extrusion in nematodes contributing to macrocyclic lactone resistance. This association was recently shown for Parascaris Pgp-11. Ivermectin resistance was correlated with the presence of three pgp-11 single nucleotide polymorphisms and/or increased pgp-11 mRNA levels. In the present study, the ability of Pgp-11 to modulate ivermectin susceptibility was investigated by its expression in a pgp-11-deficient Caenorhabditis elegans strain. Expression of Parascaris pgp-11 in two transgenic lines significantly decreased ivermectin susceptibility i...
Petit A, Redout EM, van de Lest CH, de Grauw JC, Müller B, Meyboom R, van Midwoud P, Vermonden T, Hennink WE, René van Weeren P.In this study, the intra-articular tolerability and suitability for local and sustained release of an in situ forming gel composed of an acetyl-capped poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) (PCLA-PEG-PCLA) copolymer loaded with celecoxib was investigated in horse joints. The systems were loaded with two dosages of celecoxib, 50 mg/g ('low CLB gel') and 260 mg/g ('high CLB gel'). Subsequently, they were injected into the joints of five healthy horses. For 72 h after intra-articular injection, they induced a transient inflammatory response,...
Duz M, Parkin TD, Cullander RM, Marshall JF.To evaluate ex vivo cyclooxygenase (COX) inhibition and compare in vitro and ex vivo COX-1 inhibition by flunixin meglumine and firocoxib in horses. Methods: 4 healthy horses for in vitro experiments and 12 healthy horses (6 males and 6 females; 5 Thoroughbreds, 5 Warmbloods, and 2 ponies) undergoing elective surgery for ex vivo experiments. Methods: 12 horses received flunixin meglumine (1.1 mg/kg, IV, q 12 h) or firocoxib (0.09 mg/kg, IV, q 24 h). Blood samples were collected before (baseline) and 2 and 24 hours after NSAID administration. Prostanoids (thromboxane B2, prostaglandin E2, and p...
Braganti G.In 1916 Louis Desliens, veterinary practitioner; submitted to the Academy of Sciences a description of a new way of exploring the cardiovascular system: percutaneous catheteri- zation. In 1935 he published the results of thirty years of explorations in hemodynamics mainly in horses: physiology, pathophysiology and pharmacodynamics. The text considers the very pioneering nature of these studies.
Rendle DI, Hughes KJ, Doran GS, Edwards SH.To determine the pharmacokinetics of pergolide after IV administration to horses. Methods: 8 healthy adult horses. Methods: Pergolide mesylate was administered IV at a dose of 20 μg/kg (equivalent to 15.2 μg of pergolide/kg) to each horse, and blood samples were collected over 48 hours. Pergolide concentrations in plasma were determined by means of high-performance liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were determined on the basis of noncompartmental methods. Results: After IV administration of pergolide, mean ± SD clearance, elimination half-life, a...
Kim TW, Della Rocca G, Di Salvo A, Ryschanova R, Sgorbini M, Giorgi M.To determine the pharmacokinetics of cimicoxib and to assess the inhibition of cyclooxygenase (COX) after a 5 mg/kg, single oral administration in horses that were fasted or fed. Methods: The study was conducted using an open, single dose (5 mg/kg), two treatment (fasted and fed), two-period, crossover design with a 2-week interval between dosages. Six healthy mares received 5 mg/kg of cimicoxib via nasogastric tube after fasting for 12 hours, or 2 hours after feeding. After administration, blood samples were collected for up to 24 hours and plasma used for pharmacokinetic analysis. Addi...
Roscher KA, Failing K, Moritz A.This study aimed to validate a loading and maintenance clopidogrel dosing scheme for the inhibition of platelet function, measured by whole blood impedance aggregometry in healthy adult horses. Ten Warmblood horses received oral clopidogrel once daily. Doses were based on 50 kg weight categories and resulted in one loading dose of 6-6.5 mg/kg bodyweight and maintenance doses of 1.2-1.4 mg/kg over the next 4 days. Platelet function was measured via whole blood multiple electrode impedance aggregometry prior to (T0) and at 6, 12, 24, 48, 72, 96, 144, 192 and 240 h following the loading d...
Carregaro AB, Freitas GC, Ribeiro MH, Xavier NV, Dória RG.Continuous-rate infusion (CRI) of drugs results in more stable plasma drug concentrations than administration of intermittent boluses, thus providing greater stability of physiological parameters. The aim of this study was to evaluate the physiologic and analgesic effects of the administration of morphine, butorphanol, tramadol or methadone by CRI in horses with induced synovitis of the radiocarpal joint. Results: Increased values of cardiorespiratory parameters and body temperature were observed in all groups after initiation of opioid administration, and these increases were sustained throug...
Tofflemire KL, Whitley EM, Flinn AM, Dufour VL, Ben-Shlomo G, Allbaugh RA, Griggs AN, Peterson CS, Whitley DR.To compare the effect of commercially available solution and compounded ointment formulations of dorzolamide(2%)-timolol(0.5%) on intraocular pressure (IOP) of normal horses. Methods: Eighteen clinically normal horses. Methods: A randomized, masked prospective design was used with horses divided into two equal groups. One eye of each horse was selected for topical ophthalmic treatment with either 0.2 mL of dorzolamide(2%)-timolol(0.5%) solution or 0.2 g of dorzolamide(2%)-timolol(0.5%) ointment every 12 h for 5 days. The contralateral eye of horses in both groups was untreated. Rebound tonomet...
Chiavaccini L, Claude AK, Lee JH, Ross MK, Meyer RE, Langston VC.The study objective was to compare butorphanol pharmacokinetics and physiologic effects following intravenous and subcutaneous administration in horses. Ten adult horses received 0.1 mg/kg butorphanol by either intravenous or subcutaneous injections, in a randomized crossover design. Plasma concentrations of butorphanol were measured at predetermined time points using highly sensitive liquid chromatography-tandem mass spectrometry assay (LC-MS/MS). Demeanor and physiologic variables were recorded. Data were analyzed with multivariate mixed-effect model on ranks (P ≤ 0.05). For subcutaneous i...
Holland B, Fogle C, Blikslager AT, Curling A, Barlow BM, Schirmer J, Davis JL.The objectives of this study were to compare the pharmacokinetics and COX selectivity of three commercially available formulations of firocoxib in the horse. Six healthy adult horses were administered a single dose of 57 mg intravenous, oral paste or oral tablet firocoxib in a three-way, randomized, crossover design. Blood was collected at predetermined times for PGE2 and TXB2 concentrations, as well as plasma drug concentrations. Similar to other reports, firocoxib exhibited a long elimination half-life (31.07 ± 10.64 h), a large volume of distribution (1.81 ± 0.59L/kg), and a slow clearanc...
Robinson MA, Guan F, McDonnell S, Uboh CE, Soma LR.Dermorphin is a μ-opioid receptor-binding peptide that causes both central and peripheral effects following intravenous administration to rats, dogs, and humans and has been identified in postrace horse samples. Ten horses were intravenously and/or intramuscularly administered dermorphin (9.3 ± 1.0 μg/kg), and plasma concentration vs. time data were evaluated using compartmental and noncompartmental analyses. Data from intravenous administrations fit a 2-compartment model best with distribution and elimination half-lives (harmonic mean ± pseudo SD) of 0.09 ± 0.02 and 0.76 ± 0.22 h, respe...
Ekstrand C, Bondesson U, Gabrielsson J, Hedeland M, Kallings P, Olsén L, Ingvast-Larsson C.Detection times and screening limits (SL) are methods used to ensure that the performance of horses in equestrian sports is not altered by drugs. Drug concentration-response relationship and knowledge of concentration-time profiles in both plasma and urine are required. In this study, dexamethasone plasma and urine concentration-time profiles were investigated. Endogenous hydrocortisone plasma concentrations and their relationship to dexamethasone plasma concentrations were also explored. A single dose of dexamethasone-21-isonicotinate suspension (0.03 mg/kg) was administered intramuscularly t...
Love EJ, Pelligand L, Taylor PM, Murrell JC, Sear JW.Describe the pharmacokinetics of buprenorphine and norbuprenorphine in horses and to relate the plasma buprenorphine concentration to the pharmacodynamic effects. Methods: Single phase non-blinded study. Methods: Six dedicated research horses, aged 3-10 years and weighing 480-515 kg. Methods: Thermal and mechanical nociceptive thresholds, heart and respiratory rates and locomotor activity were measured before and 15, 30, 45 & 60 minutes and 2, 4, 6, 8, 12 & 24 hours post-administration of 10 μg kg(-1) buprenorphine IV. Intestinal motility was measured 1, 6, 12 & 24 hours af...
Duz M, Parkin TD, Cullander RM, Marshall JF.To evaluate ex vivo cyclooxygenase (COX) inhibition and compare in vitro and ex vivo COX-1 inhibition by flunixin meglumine and firocoxib in horses. Methods: 4 healthy horses for in vitro experiments and 12 healthy horses (6 males and 6 females; 5 Thoroughbreds, 5 Warmbloods, and 2 ponies) undergoing elective surgery for ex vivo experiments. Methods: 12 horses received flunixin meglumine (1.1 mg/kg, IV, q 12 h) or firocoxib (0.09 mg/kg, IV, q 24 h). Blood samples were collected before (baseline) and 2 and 24 hours after NSAID administration. Prostanoids (thromboxane B2, prostaglandin E2, and p...
Zozaya H, Gutierrez L, Bernad MJ, Sumano H.Doxycyline (Dox) is a semisynthetic antibacterial drug with pharmacological advantages over its parent drug (tetracycline) in the treatment of various bacterial diseases in horses. Yet, at present a horse-customized pharmaceutical formulation is not available. Based on its pharmacokinetic/pharmacodynamic (PK/PD) ratio, Dox is considered a time-dependent antibacterial drug and ideally expected to achieve sustained plasma drug concentrations both at or slightly above the minimal inhibitory concentration (MIC) level for as long as possible between dosing intervals. Hence, the objective of this st...
McConaghy FF, Green LA, Colgan S, Morris LH.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, ...
Durham AE.Therapeutic drug monitoring and minimum inhibitory concentration (MIC) data allow more informed use of gentamicin. Objective: To measure peak and trough serum gentamicin concentrations in horses after a 6.6 mg/kg dose of gentamicin given IV and the MIC of gentamicin of bacteria for which gentamicin might be selected. Methods: Retrospective analysis of hospital records. Peak and trough plasma gentamicin concentrations were measured after 6.6 mg/kg gentamicin IV in 339 hospitalized horses. The MIC of gentamicin was measured for 503 isolates from ambulatory practice and 33 from hospital practice....
Johnson CB, Bloomfield M, Taylor PM.To investigate the effects of ketamine on the electroencephalogram (EEG) of the horse. Methods: Prospective experimental study. Methods: Eight Welsh mountain pony geldings weighing between 280 and 330 kg, 5 to 9 years old. Methods: During halothane anesthesia at an end-tidal halothane concentration between 0.75 and 0.85%, the EEG frequency power spectrum and the auditory evoked potential were recorded while an infusion of ketamine was given. Ketamine 200 mg was infused over 5 minutes in 8 ponies. The effects of ketamine on the EEG were recorded continuously during the infusion and for a furthe...
Dickey EJ, McKenzie HC, Brown KA, de Solis CN.Continuous-rate infusions (CRI) of lidocaine are often used for prolonged duration but, to date, only limited time/concentration relationships administered as a short term (24 h) CRI have been reported. Objective: To determine the time/concentration profile of lidocaine and its active metabolites glycinexylidide (GX) and monoethylglycinexylidide (MEGX) during a 96 h lidocaine infusion. Methods: Lidocaine was administered to 8 mature healthy horses as a continuous rate infusion (0.05 mg/kg bwt/min) for 96 h. Blood concentrations of lidocaine, GX and MEGX were determined using high performance l...
Valverde A, Rickey E, Sinclair M, Rioja E, Pedernera J, Hathway A, Cruz A.The effects of lidocaine combined with medetomidine or lidocaine alone on cardiovascular function during anaesthesia and their effects on recovery have not been thoroughly investigated in isoflurane-anaesthetised horses. Objective: To determine the effects of an intraoperative i.v. constant rate infusion of lidocaine combined with medetomidine (Group 1) or lidocaine (Group 2) alone on cardiovascular function and on the quality of recovery in 12 isoflurane-anaesthetised horses undergoing arthroscopy. Objective: The combination would depress cardiovascular function but improve the quality of rec...
Gokbulut C, Aksit D, Santoro M, Roncoroni C, Mariani U, Buono F, Rufrano D, Fagiolo A, Veneziano V.Mebendazole (MBZ) has been licensed for use in horses and donkeys, however there are no data available in the literature regarding its pharmacokinetic disposition and efficacy in donkeys. This study was designed to determine the plasma disposition, milk excretion and anthelmintic efficacy of MBZ in donkeys naturally infected by Cyathostominae. The animals were allocated to three groups, each of six donkeys. One group was untreated control (C-group) and the others were treated using a paste formulation of MBZ administered per os at the manufacturer's recommended horse dosage of 10 mg/kg body we...
Miyamoto A, Nishio A.The vasomotor effects of histamine on isolated bovine and equine basilar arteries were examined. Histamine induced contractions in both these preparations. The maximal response to and pEC50 value for histamine of the equine artery were larger than those of bovine tissue. Similar results were obtained with endothelium-denuded basilar arteries. Diphenhydramine (H1-receptor antagonist) inhibited histamine-induced contractions of the basilar arteries from both species in a concentration-dependent manner and its pA2 values (with 95% confidence limits) were 7.61 (7.39-7.83) and 8.15 (8.01-8.29) for ...
Kuroda T, Minamijima Y, Niwa H, Tamura N, Mita H, Fukuda K, Kaimachi M, Suzuki Y, Enoki Y, Taguchi K, Matsumoto K, Toutain PL, Bousquet-Melou A....First-generation cephalosporins have good activity against gram-positive bacteria and are extensively used in horses. There are few reports of pharmacokinetics and pharmacodynamics (PK/PD) analysis of cephalosporins in horses. Objective: To optimise the dosages of the two first-generation cephalosporins cephalothin (CET) and cefazolin (CEZ) in horses using PK/PD concepts. Methods: Experimental study with single administration. Methods: Drug plasma concentrations following a single intravenous (i.v.) administration of 22 mg/kg bodyweight (bwt) CET in 12 horses and of 10 mg/kg bwt CEZ in six h...
Rizk MA, El-Sayed SAE, Eltaysh R, Igarashi I.Equine piroplasmosis is a tick-transmitted disease that is considered one of the most serious infectious diseases affecting equines. Searching for novel antipiroplasm drugs remains indispensable due to the emergence and spreading of resistant piroplasm parasites against the limited currently used drugs, diminazene aceturate and imidocarb dipropionate. Therefore, novel drugs with specified targets need to be identified and exploited. The inhibitory effects of Medicines for Malaria Venture (MMV) Malaria Box compounds with potent in vitro anti-equine piroplasmosis activity were evaluated against ...
Hubbell JA, Muir WW, Robertson JT, Sams RA.Sodium penicillin, sodium cefazolin, and sodium citrate were administered to six adult horses on separate occasions, when awake and during anesthesia. The order of administration was randomized and studies were separated by a minimum of 7 days. Arterial blood pressure decreased significantly (less than 0.05) from control 5 minutes after intravenous (IV) sodium penicillin in awake and anesthetized horses. Systolic arterial blood pressure remained significantly (less than 0.05) decreased 10 minutes after IV sodium penicillin in anesthetized horses. Sodium cefazolin and sodium citrate did not sig...
Ringer SK, Portier K, Torgerson PR, Castagno R, Bettschart-Wolfensberger R.To compare xylazine and romifidine constant rate infusion (CRI) protocols regarding degree of sedation, and effects on postural instability (PI), ataxia during motion (A) and reaction to different stimuli. Methods: Blinded randomized experimental cross-over study. Methods: Ten adult horses. Methods: Degree of sedation was assessed by head height above ground (HHAG). Effects on PI, A and reaction to visual, tactile and acoustic stimulation were assessed by numerical rating scale (NRS) and by visual analogue scale (VAS). After baseline measurements, horses were sedated by intravenous loading dos...
Furr M, Kennedy T.Ponazuril was administered orally to 10 adult horses at 5 mg/kg body weight, once a day for 28 days. Blood was collected once a week from each horse from Days 0 through 35, daily from Days 35 through 42, and on Day 49. Cerebrospinal fluid (CSF) was also collected once a week from Day 0 through Day 49. Concentrations of ponazuril in the serum and CSF were determined, and pharmacokinetic calculations were performed. Ponazuril was readily absorbed following oral administration; and after 7 days of dosing, the serum concentration was 4.33 +/- 1.10 mg/L, and the mean CSF concentration was 0.162 +/-...
Sánchez Bruni SF, Fusé LA, Moreno L, Saumell CA, Alvarez LI, Fiel C, McKellar QA, Lanusse CE.The study of novel pharmacological strategies to control parasitism in horses is required since many parasite species have developed resistance to anthelmintic drugs. Objective: To evaluate the effects of piperonyl butoxide (PB) (a metabolic inhibitor) on the plasma availability and enantiomeric behaviour of oxfendazole (OFZ) given orally to horses, and to compare the clinical efficacy of OFZ given either alone or co-administered with PB in naturally parasitised horses. Methods: Fifteen naturally parasitised crossbred male ponies were allocated into 3 groups (n = 5) and treated orally as follo...
Schatzman U, Armbruster S, Stucki F, Busato A, Kohler I.The analgesic potency of butorphanol 25 microg/kg bodyweight (BW) and levomethadone 100 microg/kg BW, administered together with detomidine 10 microg/kg BW, was measured in twelve Warmblood horses in a randomized, blinded cross-over study. Detomidine with saline 10 ml 0.9% was used as placebo. The nociceptive threshold was determined using a constant current and a pneumatic pressure model for somatic pair Detomidine alone and in combination with butorphanol or levomethadone caused a significant temporary increase (P < 0.05) of the nociceptive threshold with a maximum effect within 15 min and a...
McFarlane D, Banse H, Knych HK, Maxwell LK.The objective of this study was to gain an understanding of the pharmacokinetic and pharmacodynamic properties of pergolide in horses with PPID after of long-term oral administration. Six horses with confirmed PPID were treated with pergolide (Prascend ) at 1 mg/horse po q24 h for 2 months, followed by 2 mg/horse po q24 h for 4 months. Following the last dose, plasma samples were collected for measurement of pergolide using an LC/MS/MS method and ACTH measurement using a chemiluminescent immunoassay. Noncompartmental and compartmental pharmacokinetic analyses were performed, as well as p...
Dhanjal JK, Wilson DV, Robinson E, Tobin TT, Dirikolu L, Dirokulu L.To determine the optimal dose, serum concentrations and analgesic effects of intravenous (IV) tramadol in the horse. Two-phase blinded, randomized, prospective crossover trial. Seven horses (median age 22.5 years and mean weight 565 kg). Horses were treated every 20 minutes with incremental doses of tramadol HCl (0.1-1.6 mg kg(-1)) or with saline. Heart rate, respiratory rate, step frequency, head height, and sweating, trembling, borborygmus and head nodding scores were recorded before and up to 6 hours after treatment. In a second study, hoof withdrawal and skin twitch reflex latencies (HWRL ...
Hardy J, Bednarski RM, Biller DS.Pharmacologically induced splenic contraction might be useful during certain medical or surgical procedures in horses. The effects of phenylephrine, an alpha 1-adrenergic receptor agonist, on hemodynamic function and splenic dimensions were examined in 6 healthy adult horses. Phenylephrine infusion (1, 3, or 6 micrograms/kg of body weight/min for 15 minutes) resulted in a dose-related increase in mean pulmonary artery pressure; right atrial pressure; systolic, mean, and diastolic arterial pressures; and packed cell volume (P = 0.0001). Concurrent decreases in heart rate and specific cardiac ou...
Belloli C, Crescenzo G, Lai O, Carofiglio V, Marang O, Ormas P.The objective of this study was to determine the pharmacokinetic behaviour of imidocarb in horses following a single i.m. injection at the dose commonly administered to treat Babesia caballi infections or to prevent babesiosis. Eight horses were injected i.m. with a single dose of 2.4 mg imidocarb dipropionate/kg bwt and blood, faecal, urine and milk samples were collected. For imidocarb determination, a high-performance liquid chromatographic method (HPLC) was used after weak cation-exchange solid phase, or liquid-liquid, extraction procedures. Twelve hours after treatment, no detectable plas...
Mosher CM, Court MH.Pharmacogenomics is the study of the impact of genetic variation on drug effects, with the ultimate goal of achieving "personalised medicine". Since the completion of the Human Genome Project, great strides have been made towards the goal of personalised dosing of drugs in people, as exemplified by the development of gene-guided dosing of the anticoagulant drug, warfarin. Although the pharmacogenomics of domestic animals is still at an early stage of development, there is great potential for advances in the coming years as the direct result of complete genome sequences currently being derived ...
Bertin FR, Ivester KM, Couëtil LL.Studies investigating the clinical efficacy of albuterol administered with the same propellant and commercially available delivery devices in horses with recurrent airway obstruction (RAO) are not currently available. Objective: To determine the efficacy of aerosolised albuterol administered to horses with RAO by means of 2 commercially available, hand-held delivery devices. Methods: Ten horses with RAO were kept in a dusty environment and fed mouldy hay to induce airway obstruction. Lung mechanics were measured before and after the procedure. ΔP(max) was measured 5 min after administration o...
Hanna CJ, Eyre P.Horses suffer from a respiratory condition, similar to human allergic asthma, that is characterized by severe dyspnea, wheezing, coughing, and mucus production. Mediator substances released during the allergic reaction may contract airways and pulmonary vasculature. Nothing is known of the effects of autacoids and other vasoactive substances on equine pulmonary vessels. Therefore, spiral strips of equine pulmonary vein were prepared in vitro and the effects of histamine (H), 5-hydroxytryptamine (5HT), bradykinin (BK), carbachol (Carb), and phenylephrine (phen) were studied. The order of contra...
Vengust M, Kerr C, Staempfli HR, Pringle J, Heigenhauser GJ, Viel L.Frusemide (Fru) is widely prescribed for management of racehorses experiencing EIPH. The effect of Fru in the lung appears to be a reduction in transcapillary pressures and inhibition of the erythrocyte anion exchange, which may lead to attenuation of transpulmonary fluid fluxes during exercise. Objective: Treatment with Fru will attenuate transpulmonary fluid fluxes in horses during high intensity exercise. Methods: In a crossover study, 6 race-fit Standardbred horses were treated with 250 mg of Fru i.v. (FruTr) or placebo (Con) 4 h before exercise on a high speed treadmill until fatigue. Art...
Machnik M, Kaiser S, Koppe S, Kietzmann M, Schenk I, Düe M, Thevis M, Schänzer W, Toutain PL.Methylxanthines positives in competition samples have challenged doping control laboratories and racing jurisdictions since methylxanthines are naturally occurring prohibited substances and often constituents of feed. For theobromine, an international threshold (renamed in International Residue Limit, IRL) of 2 µg/mL in urine has been established. On the basis of the data presented herein, a threshold or rather an IRL for theobromine in plasma of 0.3 µg/mL was proposed and was thereupon approved by the International Federation of Horseracing Authorities (IFHA). Official recommendations f...
Herring IP, Pickett JP, Champagne ES, Troy GC, Marini M.OBJECTIVE: To determine the effect of topical 1% ophthalmic atropine sulfate on intraocular pressure (IOP) in ocular normotensive horses. Animals Studied Eleven clinically healthy horses. Procedures IOP was measured bilaterally twice daily, at 8 AM and 4 PM, for 5 days. No medication was applied for the first 2 days of the study. Thereafter, one eye of each horse was treated with 0.1 mL of topical 1% atropine sulfate ointment twice daily (7 AM and 7 PM) for 3 days. The contralateral eye served as a control. In eight of the horses, an additional IOP reading was taken 3 days following cessation ...
Gozalo-Marcilla M, Luna SPL, Moreira da Silva R, Crosignani N, Lopes NP, Taylor PM, Pelligand L.Pharmacokinetic (PK)/pharmacodynamic (PD) modelling offers new insights to design protocols for sedation and analgesia in standing horses. Objective: To evaluate the parameters and interactions between detomidine and methadone when given alone or combined in standing horses. Methods: Randomised, placebo-controlled, blinded, crossover. Methods: Eight adult healthy horses were given six treatments intravenously: saline (SAL); detomidine (5 μg/kg bwt; DET); methadone (0.2 mg/kg bwt; MET) alone or combined with detomidine (2.5 [MLD], 5 [MMD] or 10 [MHD] μg/kg bwt). Venous blood samples were ob...
