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.
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...
Knych HK, Arthur RM, Mitchell MM, Holser I, Poppenga R, Smith LL, Helm MN, Sams RA, Gaskill CL.Cobalt has been used by human athletes due to its purported performance-enhancing effects. It has been suggested that cobalt administration results in enhanced erythropoiesis, secondary to increased circulating erythropoietin (EPO) concentrations leading to improvements in athletic performance. Anecdotal reports of illicit administration of cobalt to horses for its suspected performance enhancing effects have led us to investigate the pharmacokinetics and pharmacodynamic effects of this compound when administered in horses, so as to better regulate its use. In the current study, 18 horses were...
Haugaard MM, Pehrson S, Carstensen H, Flethøj M, Hesselkilde EZ, Praestegaard KF, Diness JG, Grunnet M, Jespersen T, Buhl R.Only few pharmacologic compounds have been validated for treatment of atrial fibrillation (AF) in horses. Studies investigating the utility and safety of flecainide to treat AF in horses have produced conflicting results, and the antiarrhythmic mechanisms of flecainide are not fully understood. Objective: To study the potential of flecainide to terminate acutely induced AF of short duration (≥ 15 minutes), to examine flecainide-induced changes in AF duration and AF vulnerability, and to investigate the in vivo effects of flecainide on right atrial effective refractory period, AF cycle length...
Knych HK, Steffey EP, Mitchell MM, Casbeer HC.The use of fentanyl is limited in adult horses, in part due to potential for central nervous system excitation. The pharmacokinetics and the plasma concentration-related behavioural actions of fentanyl have not been described for young foals. The goal of the present study was to describe the pharmacokinetics and behavioural effects of fentanyl following administration to the same group of foals at 3 different ages. Experimental study in healthy foals. Fentanyl was administered i.v. (4 μg/kg bwt) to a group of 9 foals on 3 separate occasions at 6–8, 20–22 and 41–42 days of age. Blood sam...
Knych HK, Steffey EP, Casbeer HC, Mitchell MM.Foal responses to a broader range of plasma fentanyl concentrations than currently reported are desirable to support (or not) clinical use. Objective: To describe fentanyl plasma concentrations following an escalating i.v. fentanyl dosing schedule in foals aged 5-13 days and describe selected, associated dose- and time-related behavioural and physiological responses to plasma fentanyl concentration. Methods: Experimental. Methods: Fentanyl was administered i.v. in an escalating fashion (2, 4, 8, 16 and 32 μg/kg bwt) at 10-min intervals. Blood samples were collected before and at selected time...
Ranheim B, Risberg ÅI, Spadavecchia C, Landsem R, Haga HA.Dexmedetomidine, the most selective α2-adrenoceptor agonist in clinical use, is increasingly being used in both conscious and anaesthetized horses; however, the pharmacokinetics and sedative effects of this drug administered alone as an infusion are not previously described in horses. Seven horses received an infusion of 8 μg dexmedetomidine/kg/h for 150 min, venous blood samples were collected, and dexmedetomidine concentrations were assayed using liquid chromatography-mass spectrometry (LC/MS) and analyzed using noncompartmental pharmacokinetic analysis. Sedation was scored as the distance...
Risberg A, Spadavecchia C, Ranheim B, Krontveit R, Haga HA.Dexmedetomidine and lignocaine IV are used clinically to provide analgesia in horses. The aims of this study were to investigate the antinociceptive effects, plasma concentrations and sedative effects of 2, 4 and 6 µg/kg/h dexmedetomidine IV, with a bolus of 0.96 µg/kg preceding each continuous rate infusion (CRI), and 20, 40 and 60 µg/kg/min lignocaine IV, with a bolus of 550 µg/kg preceding each CRI, in 10 Swiss Warmblood horses. Electrically elicited nociceptive withdrawal reflexes were evaluated by deltoid muscle electromyography. Nociceptive threshold and tolerance were determ...
Lopez BS, Giguère S, Berghaus LJ, Mullins MA, Davis JL.The objectives of this study were to investigate the pharmacokinetics of danofloxacin and its metabolite N-desmethyldanofloxacin and to determine their concentrations in synovial fluid after administration by the intravenous, intramuscular or intragastric routes. Six adult mares received danofloxacin mesylate administered intravenously (i.v.) or intramuscularly (i.m.) at a dose of 5 mg/kg, or intragastrically (IG) at a dose of 7.5 mg/kg using a randomized Latin square design. Concentrations of danofloxacin and N-desmethyldanofloxacin were measured by UPLC-MS/MS. After i.v. administration, da...
Knych HK, Steinmetz SJ, McKemie DS.The anti-anxiety and calming effects following activation of the GABA receptor have been exploited in performance horses by administering products containing GABA. The primary goal of the study reported here was to describe endogenous concentrations of GABA in horses and the pharmacokinetics, selected pharmacodynamic effects, and CSF concentrations following administration of a GABA-containing product. The mean (±SD) endogenous GABA level was 36.4 ± 12.5 ng/mL (n = 147). Sixteen of these horses received a single intravenous and oral dose of GABA (1650 mg). Blood, urine, and cerebrospin...
Kelmer G, Tatz AJ, Famini S, Bdolah-Abram T, Soback S, Britzi M.Regional limb perfusion (RLP) significantly decreases morbidity and mortality associated with distal limb injuries in horses. There is an urgent need for finding additional effective antimicrobial drugs for use in RLP. In this study, we tested the pharmacokinetics (PK) of chloramphenicol in RLP. Eight horses participated in the study, which was approved by the University Animal Care and Use Committee. The cephalic and the saphenous veins were used to perfuse the limbs. Synovial samples were collected from the metacarpo/metatarsophalangeal (MCP/MTP) joint. The Friedman Test was applied for asse...
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...
Arroyo MG, Couëtil LL, Nogradi N, Kamarudin MM, Ivester KM.The (R)-enantiomer of racemic albuterol (levalbuterol) has bronchodilatory properties whereas the (S)-enantiomer causes adverse effects in human airways, animal models, and isolated equine bronchi. Levalbuterol is commercially available and improves pulmonary function of asthmatic patients with a longer duration of effect than albuterol. Objective: To determine the dose at which inhaled levalbuterol produces maximal bronchodilatory effect (EDmax) and determine its duration of action in recurrent airway obstruction (RAO)-affected horses in comparison to racemic albuterol. Methods: Nine horses w...
Lillich JD, Bertone AL, Schmall LM, Ruggles AJ, Sams RA.OBJECTIVE--To document plasma, urine, and synovial fluid disposition of 2 common intra-articularly administered steroid preparations, methylprednisolone acetate (MPA) and isoflupredone acetate (IPA). DESIGN--Descriptive investigation. SAMPLE POPULATION--100 mg of MPA or 4 mg of IPA was administered to 2 groups of 4 healthy sound radiographically normal female horses. PROCEDURE--Blood samples were collected at time 0 (before) and 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after administration of the designated steroid. Complete urine collection for measurement of designated steroid was ac...
Moens Y, Lanz F, Doherr MG, Schatzmann U.To study the analgesic potency of the alpha2-agonist romifidine in the horse using both an electrical current and a mechanical pressure model for nociceptive threshold testing. In addition, a comparison was made with doses of detomidine and xylazine that produce equivalent degrees of sedation. Methods: Randomized, placebo-controlled, blinded cross-over study. Methods: Six adult Swiss warmblood horses, one mare and five geldings, weighing from 530 to 650 kg and aged 6-15 years. Methods: Nociceptive thresholds were measured using an electrical stimulus applied to the coronary band and using a pn...
Soraci A, Benoit E, Jaussaud P, Lees P, Delatour P.Carprofen (CPF) enantiomers and their glucuronide conjugates (GLUC) were measured in plasma and bile of horses after IV administration of the racemic compound (0.7 mg/kg of body weight). The CPF was detectable in plasma for up to 72 hours after dosing, whereas GLUC appeared early (time for maximal plasma concentration, 1 hour) and was measurable transiently at low concentration (maximal plasma concentration, 0.5 microgram/ml). The enantiospecific plasma profiles indicated a clear predominance of R-CPF, whereas the stereoselectivity of the glucuronides favored S-GLUC. At 1, 2, and 12 hours afte...
Davis JL, Schirmer J, Medlin E.Trazodone is a serotonin receptor antagonist and reuptake inhibitor used extensively as an anxiolytic in human and small animal veterinary medicine. The aims of this study were to determine the pharmacokinetics of oral trazodone in experimental horses and to evaluate the effect of oral trazodone in clinical horses. Six experimental horses were administered trazodone at 7.5 or 10 mg/kg. Plasma concentrations of trazodone and its metabolite (m-CPP) were determined via UPLC-MS/MS. Noncompartmental pharmacokinetic analysis, sedation and ataxia scores were determined. Trazodone was rapidly absorbe...
Robertson JT, Muir WW.A xylazine and butorphanol drug combination produced minimal and transient hemodynamic effects and no significant respiratory depression when administered to 6 healthy horses. Combining xylazine and butorphanol produced a synergistic analgesic effect and provided good chemical restraint for a standing surgical procedure.
Calzetta L, Rogliani P, Mattei M, Alfonsi P, Cito G, Pistocchini E, Cazzola M, Matera MG.Equine airways represent a suitable ex vivo model to study the functional impact of pharmacological treatments on human chronic obstructive pulmonary disorders, such as asthma and chronic obstructive pulmonary disease (COPD). We aimed to characterize the pharmacological interaction between the long-acting muscarinic antagonist (LAMA) tiotropium and the long-acting β-agonist (LABA) olodaterol in equine airways. The effect of tiotropium and olodaterol, administered alone and in combination at the ratio of concentrations reproducing ex vivo the concentration-ratio delivered by the currently avai...
Risberg A, Spadavecchia C, Ranheim B, Krontveit R, Haga HA.Dexmedetomidine and lignocaine IV are used clinically to provide analgesia in horses. The aims of this study were to investigate the antinociceptive effects, plasma concentrations and sedative effects of 2, 4 and 6 µg/kg/h dexmedetomidine IV, with a bolus of 0.96 µg/kg preceding each continuous rate infusion (CRI), and 20, 40 and 60 µg/kg/min lignocaine IV, with a bolus of 550 µg/kg preceding each CRI, in 10 Swiss Warmblood horses. Electrically elicited nociceptive withdrawal reflexes were evaluated by deltoid muscle electromyography. Nociceptive threshold and tolerance were determ...
Rütten S, Schrödl W, Abraham G.Glucocorticoids are important drugs in the treatment of many inflammatory, autoimmune and allergic diseases in humans and animals. We investigated the effects of hydrocortisone and dexamethasone on TNF-α, IL-1Ra and INF-γ release in stimulated whole blood cell culture from healthy horses. Whole blood cell cultures proved to be useful for the characterization of the anti-inflammatory properties of new drugs. Diluted equine whole blood was exposed to lipopolysaccharide (LPS) and PCPwL (a cocktail consisting of phythemagglutinin E, concanavalin A, pokeweed mitogen and lipopolysaccharide) in the...
Chapuis RJJ, Smith JS, Uehlinger FD, Meachem M, Johnson R, Dowling PM.The objectives of this study were to investigate the pharmacokinetics (PK), pharmacodynamics (PD), and the efficacy of oral administration of doxycycline (DXC) in horses with Streptococcus zooepidemicus tissue infections. Tissue chambers (TC) were implanted subcutaneously in the cervical region of 7 horses and inoculated with a single S. zooepidemicus isolate with a minimum inhibitory concentration (MIC) of 0.25 µg/ml, determined by agar dilution. Doxycycline hyclate (10 mg/kg, orally, q 12 h, for 5 days) mixed with poloxamer gel was started following inoculation. The TC fluid was samp...
Rossier Y, Divers TJ, Sweeney RW.The urinary GGT/urinary creatinine (uGGT/uCR) ratio was measured on Days 1, 3 and 10 in 4 adult, healthy horses; in 6 adult, healthy horses treated with gentamicin at recommended dosages and 9 adult horses treated for pleuropneumonia with gentamicin at recommended dosages. Plasma creatinine and gentamicin trough concentrations were measured on the same days. The uGGT/uCr ratio was higher in the normal horses (mean +/- s.d. 22.85 +/- 13.69) than previously reported normal values (10.5 +/- 6.8) (Adams and McClure 1985). Analysis of variance for repeated measures was used to compare the ratio in ...
Thomasy SM, Mama KR, Whitley K, Steffey EP, Stanley SD.In order to evaluate its potential as an adjunct to inhalant anaesthesia in horses, the pharmacokinetics of fentanyl must first be determined. Objective: To describe the pharmacokinetics of fentanyl and its metabolite, N-[1-(2-phenethyl-4-piperidinyl)maloanilinic acid (PMA), after i.v. administration of a single dose to horses that were awake in Treatment 1 and anaesthetised with isoflurane in Treatment 2. Methods: A balanced crossover design was used (n = 4/group). During Treatment 1, horses received a single dose of fentanyl (4 microg/kg bwt, i.v.) and during Treatment 2, they were anaesthet...
Aristizabal FA, Nieto JE, Guedes AG, Dechant JE, Yamout S, Morales B, Snyder J.Regional limb perfusion (RLP) in horses has proven to be a simple and effective technique for the treatment of synovial and musculoskeletal infections in the distal portion of the limbs. The ideal tourniquet time needed to achieve therapeutic synovial concentrations remains unknown. The pharmacokinetic effects of general anesthesia (GA) versus standing sedation (SS) RLP on synovial amikacin concentrations are not completely understood. This study investigated the pharmacokinetic effects of RLP under general anesthesia (GA) versus standing sedation (SS) on synovial amikacin concentration follow...
Söbbeler FJ, Kästner SB.To evaluate the transdermal local anaesthetic effect of lidocaine or lidocaine combined with prilocaine or tetracaine in horses. Methods: Experimental, randomized study. Methods: A total of five healthy adult warmblood horses. Methods: Horses were clipped bilaterally at the withers, cranial saddle area and caudal saddle area. Baseline measurements for mechanical superficial sensation via von Frey filaments and nociceptive thermal thresholds were performed. A 5% lidocaine patch (12 hour exposure, treatment L), a lidocaine/prilocaine cream (each 2.5%, treatment LP) and a lidocaine/tetracaine cre...
Skarda RT, Muir WW.To examine effects of 0.25 mg of xylazine/kg of body weight diluted to a total volume of 6 ml/450 kg with sterile 0.9% NaCl, administered into the epidural space of the sacrococcygeal joint on perineal analgesia, sedation, ataxia, and respiratory and cardiovascular function in standing mares. Methods: Randomized, blinded study, using xylazine (treatment) and 0.9% NaCl (controls). At least 2 weeks elapsed between the treatments. Methods: Eight healthy mares. Methods: Blood samples were drawn. Systemic hemodynamics were determined, including cardiac output and pulmonary arterial, systemic arteri...
Tudor RA, Papich MG, Redding WR.To evaluate pharmacokinetics of once daily i.v. administration of gentamicin sulfate to adult horses that had abdominal surgery. Methods: Prospective study. Methods: 28 adult horses that underwent abdominal surgery for colic. Methods: 14 horses were treated with each dosage of gentamicin (i.e., 6.6 or 4 mg/kg, i.v., q 24 h) and blood samples were collected for pharmacokinetic analysis. Plasma gentamicin concentrations were measured by use of a fluorescence polarization immunoassay. Pharmacokinetic analysis measured the elimination half-life, volume of distribution, and gentamicin total systemi...
Stine JM, Michau TM, Williams MK, Kuebelbeck KL, Stengard ME.Original study. Objective: To evaluate the effect of sedation with romifidine hydrochloride 1% (Sedivet: Boehringer-Ingelheim) on intraocular pressure (IOP) in the normal horse and horses with incidental ophthalmic findings as measured by applanation tonometry. Methods: Nineteen clinically normal horses (13 geldings, six mares) and eight horses (three geldings, five mares) with incidental ophthalmic findings were included in this study. Methods: All horses underwent complete ophthalmic examination with pharmacologic mydriasis a minimum of 2 weeks prior to IOP evaluation. Baseline intraocular p...
Hébert L, Guitton E, Madeline A, Géraud T, Carnicer D, Lakhdar L, Pitel PH, Coste M, Laloy E, Giraudet A, Zientara S, Büscher P, Laugier C, Hans A....Trypanosoma equiperdum, the causative agent of dourine, may affect the central nervous system, leading to neurological signs in infected horses. This location protects the parasite from most (if not all) existing chemotherapies. In this context, the OIE terrestrial code considers dourine as a non-treatable disease and imposes a stamping-out policy for affected animals before a country may achieve its dourine-free status. The use of practices as drastic as euthanasia remains controversial, but the lack of a suitable tool for studying a treatment's efficacy against dourine hampers the developmen...
Abraham G, Brodde OE, Ungemach FR.In 12 healthy horses, the effects of the beta2-agonist clenbuterol and the glucocorticoid dexamethasone on the lymphocyte beta2-adrenoceptor density and affinity (determined by (-)-[125I]-iodocyanopindolol binding) as well as its responsiveness (assessed by lymphocyte cyclic AMP [cAMP] responses to 10 micromol/l (-)-isoprenaline) were studied. Clenbuterol treatment, 2 x 0.8 microg/kg/day i.v. for 12 days, decreased significantly ICYP binding sites by approximately 30-40%; concomitantly, lymphocyte cAMP response to (-)-isoprenaline was reduced. After withdrawal of clenbuterol, beta2-adrenocepto...
Pérez R, Godoy C, Palma C, Cabezas I, Muñoz L, Rubilar L, Arboix M, Alvinerie M.A study was undertaken in order to evaluate and compare ivermectin's (IVM) plasma disposition kinetic parameters after oral or intramuscular (IM) administration in horses. Ten clinically healthy adult horses, weighing 380-496 kg body weight (BW), were allocated to two experimental groups of five horses. Group I, was treated with an oral paste formulation of IVM at the manufacturer's recommended dose of 0.2 mg/kg BW. Group II, was treated IM with an injectable 1% formulation of IVM at a dose of 0.2 mg/kg BW. Blood samples were collected by jugular puncture at different times between 0.5 h and 7...
Leathwick DM, Sauermann CW, Geurden T, Nielsen MK.A previously described model for the dynamics of the parasitic stages of Parascaris spp. was modified to include eggs outside the host and the genetics of anthelmintic resistance before being used to address questions regarding the development of resistance. Three broad questions were addressed; i) How sustainable is the current common practice of treating foals monthly for their first year of life (i.e. 12 treatments/year)? ii) Does the timing of treatments have an effect on resistance development? (i.e. do certain treatments select for resistance more strongly than others?), and iii) How sus...
Saes IL, Vera JHS, Fachiolli DF, Yamada PH, Dellaqua JVT, Saes RL, Amarante AFT, Soutello RVG.The aim of this study was to determine the time required by different anthelmintic agents to reduce strongyle egg shedding in horses. Fifty horses were divided into five homogenous groups based on faecal egg counts (FECs). Treatment groups received either ivermectin; moxidectin; fenbendazole; piperazine; or no treatment (control group). Faecal examinations were performed 4, 8, 12, 18, 24, 36 and 48h after the anthelmintic treatment. After this period, faecal samples were taken every 24h over the next 12days and finally on alternate days (48-h intervals) for another 14days until the end of the ...
Ström L, Dalin F, Domberg M, Stenlund C, Bondesson U, Hedeland M, Toutain PL, Ekstrand C.Topical ophthalmic atropine sulfate is an important part of the treatment protocol in equine uveitis. Frequent administration of topical atropine may cause decreased intestinal motility and colic in horses due to systemic exposure. Atropine pharmacokinetics are unknown in horses and this knowledge gap could impede the use of atropine because of the presumed risk of unwanted effects. Additional information could therefore increase safety in atropine treatment. Results: Atropine sulfate (1 mg) was administered in two experiments: In part I, atropine sulfate was administered intravenously and t...
Bousquet-Mélou A, Schneider M, El Garch F, Broussou DC, Ferran AA, Lallemand EA, Triboulloy C, Damborg P, Toutain PL.Marbofloxacin (MBX), a fluoroquinolone (FQ), is considered as a critical antibiotic requiring antimicrobial susceptibility testing (AST) for prudent use. No clinical breakpoint (CBP) currently exists to interpret the results of such tests in horses. Objective: To compute PK/PD cut-offs (PK/PDCO ) that is one of the three minimum inhibitory concentrations (MICs) considered establishing a CBP for antimicrobial susceptibility test interpretation. Methods: A meta-analysis conducted by combining five sets of previously published pharmacokinetic data, obtained in clinical and nonclinical settings. M...
Pippi NL, Lumb WV.An equine model, subjected to three kinds of pain (superficial, deep, and visceral) was used to test effects of analgesic drugs. Two groups of ponies were used. In the first group of six ponies, six drugs (fentanyl, meperidine, methadone, oxymorphone, pentazocine, and xylazine) were given according to a Latin square experimental design, and tests were made at 30-minute intervals for 4 hours. Mean values (control) for the three kinds of pain were obtained before and after the tests and were compared with the mean values (drugs) obtained over 2- and 4-hour intervals (four and eight measurements ...
Elliott J.Rings of equine digital vein examined under conditions of isometric tension recording constricted to alpha-adrenoceptor agonists with an order of potency of 5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline bitartrate (UK 14304) = noradrenaline > 6-Allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d) azepine (BHT-920) > phenylephrine > dopamine > methoxamine. The maximum force generated was greatest for the non-selective agonist noradrenaline and lowest for the alpha2-selective agonist BHT-920 with the other agonists between these two extremes. Selective inactivation of alpha1-adreno...
Newman JC, Prange T, Jennings S, Barlow BM, Davis JL.The objectives of this study were to examine the pharmacokinetics of tobramycin in the horse following intravenous (IV), intramuscular (IM), and intra-articular (IA) administration. Six mares received 4 mg/kg tobramycin IV, IM, and IV with concurrent IA administration (IV+IA) in a randomized 3-way crossover design. A washout period of at least 7 days was allotted between experiments. After IV administration, the volume of distribution, clearance, and half-life were 0.18 ± 0.04 L/kg, 1.18 ± 0.32 mL·kg/min, and 4.61 ± 1.10 h, respectively. Concurrent IA administration could not be...
Jacobson GA, Pirie A, Edwards S, Hughes KJ, Rendle DI, Davies NW.Pergolide, an ergot-derived dopamine D2 receptor agonist, is used extensively as an orally administered treatment for pituitary pars intermedia dysfunction (PPID) in horses. One of the barriers associated with pergolide determinations in plasma for pharmacokinetic applications has been the technically demanding requirement for sensitivity. The objective of our work was to develop a simple assay for the determination of pergolide in plasma and demonstrate its potential application in the study of pergolide pharmacokinetics (PK) in horses. A UPLC-MS/MS assay was developed with a simple sample pr...
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...
