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.
Oswald S, Peters J, Venner M, Siegmund W.Clarithromycin (CLA) is a well established macrolide antibiotic which is frequently used in therapy of airway diseases in foals. It is extensively metabolized by CYP3A4 resulting in the antimicrobial active metabolite 14-hydroxyclarithromycin (OH-CLA). Rifampicin (RIF) is often comedicated to prevent resistance and augment therapy. RIF is a known inducer for metabolizing enzymes and transporter proteins. Therefore, comedication might bare the risks of pharmacokinetic drug interactions which were investigated in a clinical trial. As no adequate method to determine CLA, RIF and their main metabo...
Davis JL, Marshall JF, Papich MG, Blikslager AT, Campbell NB.The purpose of this study was to determine the pharmacokinetics of deracoxib following oral administration to horses. In addition, in vitro equine whole blood cyclooxygenase (COX) selectivity assays were performed. Six healthy adult horses were administered deracoxib (2 mg/kg) orally. Plasma samples were collected prior to drug administration (time 0), and 10, 20, 40 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after administration for analysis with high pressure liquid chromatography using ultraviolet detection. Following PO administration, deracoxib had a long elimination half-life (t(...
Matera MG, Calzetta L, Rogliani P, Bardaro F, Page CP, Cazzola M.Equine obstructive pulmonary disease, also known as heaves or recurrent airway obstruction (RAO) is a common equine pulmonary disease with some similarities to human asthma and COPD, which represents a major cause of morbidity and loss of lung performance. Salbutamol has been widely used for the treatment of human airway diseases and has usually been prepared as the racemic form of the drug. However, recently the R-enantiomer of salbutamol has been introduced into clinical practice in the treatment of asthma in humans and this has been suggested to be an improvement on the racemic form of the ...
Dillon PF, Root-Bernstein R, Robinson NE, Abraham WM, Berney C.Previous in vitro research demonstrated that ascorbate enhances potency and duration of activity of agonists binding to alpha 1 adrenergic and histamine receptors. Objective: Extending this work to beta 2 adrenergic systems in vitro and in vivo. Methods: Ultraviolet spectroscopy was used to study ascorbate binding to adrenergic receptor preparations and peptides. Force transduction studies on acetylcholine-contracted trachealis preparations from pigs and guinea pigs measured the effect of ascorbate on relaxation due to submaximal doses of beta adrenergic agonists. The effect of inhaled albuter...
Cox S, Yarbrough J.A new method of analysis has been developed and validated for the determination of firocoxib, a new nonsteroidal anti-inflammatory drug (NSAID) approved for use in horses and dogs to control pain and inflammation associated with osteoarthritis. Following a liquid extraction using ethyl acetate:hexane (40:60), samples were separated by isocratic reversed-phase HPLC on a Sunfire C(18) column and quantified using UV detection at 290 nm. The mobile phase was a mixture of water with 0.025% trifluoroacetic acid and acetonitrile, with a flow-rate of 1.1 ml/min. The procedure produced a linear curve o...
Hall TL, Tell LA, Wetzlich SE, McCormick JD, Fowler LW, Pusterla N.Ceftiofur, a third generation cephalosporin, demonstrates in vitro efficacy against microorganisms isolated from septicemic neonatal foals. This pharmacokinetic study evaluated the intravenous and subcutaneous administration of ceftiofur sodium (5 mg/kg body weight; n = 6 per group) and subcutaneous administration of ceftiofur crystalline free acid (6.6 mg/kg body weight; n = 6) in healthy foals. Plasma ceftiofur- and desfuroylceftiofur-related metabolite concentrations were measured using high performance liquid chromatography following drug administration. Mean (±SD) noncompartmental pharma...
Winther L, Baptiste KE, Friis C.Cefquinome concentrations, following intravenous and aerosol administration to horses, in pulmonary epithelial lining fluid (PELF) were examined and compared to plasma concentrations. Single dose of cefquinome sulphate (1 mg/kg) was administered intravenously to six horses followed by a single aerosol administration (225 mg) with a wash-out period of 14 days between treatments. After each drug administration, cefquinome concentrations in plasma and PELF, obtained by intrabronchial cotton swabs, were determined. After intravenous administration, cefquinome concentrations in plasma declined fast...
Clutton RE.Opioid analgesics have been the foundation of human pain management for centuries, and their value in animals has increased since it was proposed that it is the veterinarian's duty to alleviate pain whenever it may occur. Compared with other domesticated species, the horse has benefitted less from the increased understanding of opioid pharmacology in animals, because early literature was overlooked and later work, which examined adverse side effects rather than analgesia, concluded that analgesic and excitatory doses were irreconcilably close. More recent studies have indicated a widening role...
Muir WW.N-Methyl-D-aspartate (NMDA) is a synthetic chemical binding molecule (ligand) that selectively binds to the "slow response" glutamate NMDA receptor (NMDAR). NMDARs are important for normal brain function and play a central role in learning, memory, and the development of central nervous system hyperactive states. Diverse chemicals belonging to various drug families have demonstrated NMDAR antagonistic effects. Ketamine has been shown to produce antihyperalgesic effects produced by incision and tissue or nerve damage, and has become popular in equine practice as an anesthetic and more recently ...
Giorgi M, Cuniberti B, Ye G, Barbero R, Sgorbini M, Vercelli C, Corazza M, Re G.Tepoxalin is a non-steroidal anti-inflammatory drug with analgesic, anti-inflammatory, and antipyretic properties and has been recently introduced into veterinary medicine. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profile of tepoxalin to assess whether it would be suitable for clinical use in horses. Six female fasting/fed horses were given 10mg/kg tepoxalin orally in a cross-over study. After administration, tepoxalin underwent rapid and extensive hydrolytic conversion to its carboxylic acid metabolite RWJ-20142. In animals that had been fed, the plasm...
Li XQ, Uboh CE, Soma LR, Guan FY, You YW, Kahler MC, Judy JA, Liu Y, Chen JW.A non-aqueous capillary electrophoresis-mass spectrometry (NACE-MS) method was developed for simultaneous separation and identification of 12 amphetamine and related compounds in equine plasma. Analytes were recovered from plasma by liquid-liquid extraction using methyl tertiary butyl ether (MTBE). A bare fused-silica capillary was used for separation of the analytes. Addition of sheath liquid to the capillary effluent allowed the detection of the analytes by positive electrospray ionization mass spectrometry using full scan data acquisition. The limit of detection (LOD) for the target analyte...
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...
Terry RL, McDonnell SM, Van Eps AW, Soma LR, Liu Y, Uboh CE, Moate PJ, Driessen B.Gabapentin is being used in horses although its pharmacokinetic (PK) profile, pharmacodynamic (PD) effects and safety in the equine are not fully investigated. Therefore, we characterized PKs and cardiovascular and behavioral effects of gabapentin in horses. Gabapentin (20 mg/kg) was administered i.v. or p.o. to six horses using a randomized crossover design. Plasma gabapentin concentrations were measured in samples collected 0-48 h postadministration employing liquid chromatography-tandem mass spectrometry. Blood pressures, ECG, and sedation scores were recorded before and for 12 h after gaba...
Pimenta EL, Teixeira Neto FJ, Sá PA, Pignaton W, Garofalo NA.Bradycardia may be implicated as a cause of cardiovascular instability during anaesthesia. Objective: Hyoscine would induce positive chronotropism of shorter duration than atropine, without adversely impairing intestinal motility in detomidine sedated horses. Methods: Ten minutes after detomidine (0.02 mg/kg bwt, i.v.), physiological saline (control), atropine (0.02 mg/kg bwt) or hyoscine (0.2 mg/kg bwt) were randomly administered i.v. to 6 horses, allowing one week intervals between treatments. Investigators blinded to the treatments monitored cardiopulmonary data and intestinal auscultation ...
Dimaio Knych HK, Steffey EP, Stanley SD.Yohimbine is an alpha 2 adrenergic receptor antagonist, which has been shown to counteract the CNS depressant effects of alpha 2 receptor agonists in a number of species. Recently, our laboratory identified yohimbine in the absence of detectable concentrations of an alpha 2 agonist in a regulatory sample collected from a horse racing in California. This coupled with anecdotal reports of CNS stimulation and documented reports of cardiovascular changes when administered in conjunction with an agonist led us to investigate the pharmacokinetics and pharmacodynamics of yohimbine when administered a...
Nagata S, Yamashita S, Kurosawa M, Kuwajima M, Hobo S, Katayama Y, Anzai T.To determine the pharmacokinetics and tissue distribution of minocycline in horses. Methods: 5 healthy Thoroughbred mares for the pharmacokinetic experiment and 6 healthy Thoroughbred mares for the tissue distribution experiment. Methods: Each mare was given 2.2 mg of minocycline hydrochloride/kg, IV. Blood samples were collected once before minocycline administration (0 hours) and 10 times within 48 hours after administration in the pharmacokinetics study, and 24 tissue samples were obtained at 0.5 and 3 hours in the distribution study. Results: No adverse effects were observed in any of the ...
Winther L, Guardabassi L, Baptiste KE, Friis C.Sulfadiazine (SDZ) and trimethoprim (TMP) concentrations were examined in plasma and pulmonary epithelial lining fluid (PELF), following intravenous and oral administration and compared to minimum inhibitory concentrations (MICs) of common bacterial isolates from equine lower airway infections. SDZ/TMP (25/5 mg/kg) was administered intravenously, intragastric or per os to fed horses, and blood samples were collected before and 11 times, over 24 h, after administration. PELF samples were collected via a tampon device four times after drug administration and analysed for drug concentrations. Add...
Pinto N, Schumacher J, Taintor J, Degraves F, Duran S, Boothe D.No studies have determined the pharmacokinetics of low-dose amikacin in the mature horse. Objective: To determine if a single i.v. dose of amikacin (10 mg/kg bwt) will reach therapeutic concentrations in plasma, synovial, peritoneal and interstitial fluid of mature horses (n=6). Methods: Drug concentrations of amikacin were measured across time in mature horses (n=6); plasma, synovial, peritoneal and interstitial fluid were collected after a single i.v. dose of amikacin (10 mg/kg bwt). Results: The mean±s.d. of selected parameters were: extrapolated plasma concentration of amikacin at time ze...
Kleinheinz J, Jung S, Wermker K, Fischer C, Joos U.Current approaches in bone regeneration combine osteoconductive scaffolds with bioactive cytokines like BMP or VEGF. The idea of our in-vitro trial was to apply VEGF165 in gradient concentrations to an equine collagen carrier and to study pharmacological and morphological characteristics of the complex in a circulation model. Methods: Release kinetics of VEGF165 complexed in different quantities in a collagen matrix were determined in a circulation model by quantifying protein concentration with ELISA over a period of 5 days. The structural changes of the collagen matrix were assessed with lig...
Grady JA, Davis EG, Kukanich B, Sherck AB.To assess pharmacokinetic and pharmacodynamic properties of dexamethasone administered PO as a solution or powder, compared with properties of dexamethasone solution administered IV, in apparently healthy horses. Methods: 6 adult horses. Methods: Serum cortisol concentration for each horse was determined before each treatment (baseline values). Dexamethasone (0.05 mg/kg) was administered PO (in solution or powdered form) or IV (solution) to horses from which feed had or had not been withheld (unfed and fed horses, respectively). Each horse received all 6 treatments in random order at 2-week in...
Martinez M, Modric S.In veterinary medicine, the characterization of a drug's pharmacokinetic (PK) properties is generally based upon data that are derived from studies that employ small groups of young healthy animals, often of a single breed. These are also the data from which population predictions are often generated to forecast drug exposure characteristics in the target population under clinical conditions of use. In veterinary medicine, it is rare to find information on the covariates that can influence drug exposure characteristics. Therefore, it is important to recognize some of the factors that can alter...
Leclere M, Lefebvre-Lavoie J, Beauchamp G, Lavoie JP.Orally administered prednisolone and dexamethasone are used commonly in the treatment of recurrent airway obstruction (RAO) in horses. However, the efficacy of prednisolone in improving pulmonary function during continuous antigen exposure has not been evaluated critically and there is little evidence supporting the efficacy of low-dose oral dexamethasone in the same conditions. Objective: Oral prednisolone and dexamethasone improve pulmonary function in RAO under conditions of continuous antigen exposure, and dexamethasone is more effective than prednisolone at commonly used dosages. Methods:...
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...
Toutain PL.For legitimate medications, veterinarians must advise the owners or trainers of horses on appropriate withholding times after a treatment, to avoid the risk of incurring a positive drug test. Objective: To explore the safety span to select that a veterinarian may extrapolate a tailored withdrawal time (WT) from a generic detection time (DT) as published by the European Horserace Scientific Liaison Committee (EHSLC). Methods: Using Monte Carlo simulations, it was shown that for a low variability of pharmacokinetic parameters (CV=20%), an uncertainty span of about 40% may be selected to transfor...
Schmitz A, Thormann W, Moessner L, Theurillat R, Helmja K, Mevissen M.Ketamine, an injectable anesthetic and analgesic consisting of a racemic mixture of S-and R-ketamine, is routinely used in veterinary and human medicine. Nevertheless, metabolism and pharmacokinetics of ketamine have not been characterized sufficiently in most animal species. An enantioselective CE assay for ketamine and its metabolites in microsomal preparations is described. Racemic ketamine was incubated with pooled microsomes from humans, horses and dogs over a 3 h time interval with frequent sample collection. CE data revealed that ketamine is metabolized enantioselectively to norketamine...
Toutain PL.In racing and other equine sports, it is possible to increase artificially both the physical capability and the presence of a competitive instinct, using drugs, such as anabolic steroids and agents stimulating the central nervous system. The word doping describes this illegitimate use of drugs and the primary motivation of an equine anti-doping policy is to prevent the use of these substances. However, an anti-doping policy must not impede the use of legitimate veterinary medications and most regulatory bodies in the world now distinguish the control of illicit substances (doping control) from...
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 ...
Pérez R, Godoy C, Palma C, Muñoz L, Arboix M, Alvinerie M.A study was done to compare plasma disposition kinetics and the fecal elimination profile of doramectin (DRM) after oral or intramuscular (IM) administration in horses. Ten clinically healthy horses, 328-502 kg body weight (bw), were assigned to 2 experimental groups of 5 horses each. Group 1 was treated with an oral dose of 0.2 mg DRM/kg bw, while Group 2 was treated with 0.2 mg DRM/kg bw by IM route. Blood and fecal samples were collected at different times between 0.5h and 60 days post-treatment. After plasma and fecal drug extraction and derivatization, samples were analysed by high perfor...
Mama KR, Grimsrud K, Snell T, Stanley S.Detomidine hydrochloride is used to provide sedation, muscle relaxation and analgesia in horses, but a lack of information pertaining to plasma concentration has limited the ability to correlate drug concentration with effect. Objective: To build on previous information and assess detomidine for i.v. and i.m. use in horses by simultaneously assessing plasma drug concentrations, physiological parameters and behavioural characteristics. Objective: Systemic effects would be seen following i.m. and i.v. detomidine administration and these effects would be positively correlated with plasma drug con...
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 ...
Wetmore LA, Pascoe PJ, Shilo-Benjamini Y, Lindsey JC.OBJECTIVE To determine the locomotor response to the administration of fentanyl in horses with and without the G57C polymorphism of the μ-opioid receptor. ANIMALS 20 horses of various breeds and ages (10 horses heterozygous for the G57C polymorphism and 10 age-, breed-, and sex-matched horses that did not have the G57C polymorphism). PROCEDURES The number of steps each horse took was counted over consecutive 2-minute periods for 20 minutes to determine a baseline value. The horse then received a bolus of fentanyl (20 μg/kg, IV), and the number of steps was again counted during consecutive 2-...
Kamerling SG, Dequick DJ, Weckman TJ, Sprinkle FP, Tobin T.The effects of procaine, mepivacaine and phenylbutazone on pain perception in the equine were studied using two behavioral assays of nociception; the thermal evoked hoof withdrawal reflex and skin twitch reflex. Pain perception threshold was measured as the latency from onset of thermal stimuli to reflex withdrawal of the forelimb or contraction of the cutaneous musculature. Procaine 2% and mepivacaine 2% prolonged the hoof withdrawal reflex latency when administered locally by producing a block of the palmar and metacarpal nerves. Significant analgesia lasted 90 min and 210 min for procaine a...
Lallemand E, Trencart P, Tahier C, Dron F, Paulin A, Tessier C.To evaluate pharmacokinetic-pharmacodynamic variables and local tolerance at injection-site of marbofloxacin administered via regional intravenous limb perfusion (RIVLP) in standing horses. Methods: Adult horses (n = 6). Methods: RIVLP were performed with rubber tourniquets applied to the forelimbs of standing sedated horses. Marbofloxacin (0.67 mg/kg) was randomly injected in 1 forelimb, with the contralateral limb serving as a control (0.9% NaCl solution). Samples of jugular blood and synovial fluid from the radiocarpal joint of the marbofloxacin-perfused limb were collected before and...
Davis JL, Stewart T, Brazik E, Gilger BC.The purpose of this study was to determine the influence of age, breed and gender on vertical pupil diameter (VPD) following a single dose of 1% atropine sulfate ophthalmic solution in the normal equine eye. Methods: Thirty-two horses of various ages, breeds and genders were included. The horses had no history or clinical signs of ophthalmic disease. All horses studied had darkly pigmented irides. Methods: Two milligrams of 1% atropine sulfate ophthalmic solution was topically administered as a single dose in the right eye of each horse on Day 0. The VPD (mm) was measured in both eyes using di...
LeBlanc PH.Chemical restraint can be a useful pharmacologic tool to assist the veterinarian performing surgery in the standing horse. The agents discussed impose minimal adverse side effects and are considered relatively safe when administered in the doses described. Acetylpromazine, the most widely used tranquilizer, produces mild sedation but no analgesia. The use of tranquilizers for surgical procedures requires the combined use of either a local anesthetic technique or a sedative-hypnotic or opiate to provide analgesia. Sedative-hypnotics such as xylazine and detomidine or opiates such as morphine an...
Moore BR.Interferons are efficacious therapeutic agents for treatment of several clinically important diseases in cattle and horses. In some instances, the therapeutic goal of IFN administration is prevention or clinical cure of acute viral infections. On the other hand, IFN may serve as adjunctive treatment to diminish clinical manifestations of disease and improve the quality of life. Oral administration of IFN alpha appears to be a safe and convenient route of administration, and the therapeutic benefit likely develops via unique mechanisms involving oropharyngeal-associated lymphoid tissue for diss...
Steffey EP, Kelly AB, Farver TB, Woliner MJ.Circulatory and respiratory effects of intravenously administered acetylpromazine (0.033 and 0.067 mg/kg) and xylazine (0.5 and 1.0 mg/kg) were studied in drug cross-over fashion in eight laterally recumbent horses anesthetized only with halothane (1.06%, end-tidal) in O2. Both doses of acetylpromazine caused a significant and sustained elevation in cardiac output via a rise in stroke volume. Xylazine produced an initial significant fall in cardiac output followed by a return to control levels. Halothane anesthesia did not prevent xylazine-related atrioventricular conduction block. All treatme...
Brown MP, Stover SM, Kelly RH, Farver TB, Knight HD.Six adult mares were given a single intravenous injection of oxytetracycline HCl (50 mg/ml) at a dosage of 5 mg/kg. Serum, synovial fluid, peritoneal fluid, and urine oxytetracycline concentrations were measured serially over a 48-h period. The highest measured serum oxytetracycline concentration was 8.01 mcg/ml at 1/2 h. Oxytetracycline was detected in synovial fluid and peritoneal fluid, which obtained mean peak oxytetracycline concentrations of 4.43 mcg/ml and 4.20 mcg/ml, at 1/2 h and 1 h, respectively. These concentrations steadily declined in parallel with serum concentrations and were n...
Forro M, Lindinger MI.Frusemide (Lasix) is commonly used diuretic in horse racing and equine clinical practice. While pharmacology, pharmacodynamics, renal and haematological effects of frusemide have been studied in horses, its effects on the distribution of fluid within the horse remain unknown. Objective: To quantify the effects of frusemide on extracellular and intracellular fluid shifts. Methods: Horses were infused with 1 mg/kg body mass (n = 7) or 2 mg/kg (n = 9) i.v. frusemide. Total body water (TBW), extracellular fluid volume (ECFV) and plasma volume (PV) were measured using D2O, NaSCN and Evans blue dilu...
Ivermectin (IVM) is an anthelmintic compound commonly used off-label in mules due to its broad-spectrum of activity. Despite the general use of IVM in mules with the same dose and route of administration licensed for horses, significant pharmacokinetic differences might exist between horses and mules, as already observed for donkeys. The aim of the present study was to evaluate the pharmacokinetic profile and anthelmintic efficacy of an oral paste of IVM in mules naturally infected with cyathostomins. Fifteen adult mules with fecal egg counts (FEC) ≥200 eggs per gram (EPG), with exclusive pr...
Goudah A, Abo El-Sooud K, Shim JH, Shin HC, Abd El-Aty AM.The target of the present study was to investigate the plasma disposition kinetics of levofloxacin in stallions (n = 6) following a single intravenous (i.v.) bolus or intramuscular (i.m.) injection at a dose rate of 4 mg/kg bwt, using a two-phase crossover design with 15 days as an interval period. Plasma samples were collected at appropriate times during a 48-h administration interval, and were analyzed using a microbiological assay method. The plasma levofloxacin disposition was best fitted to a two-compartment open model after i.v. dosing. The half-lives of distribution and elimination were...
Sullins KE, Messer NT, Nelson L.Twenty-one adult horses were randomly assigned into 7 groups of 3 and were treated for 5 days with procaine penicillin G, benzathine penicillin , or phenylbutazone in various combinations and dosage schedules. Serum concentration of penicillin was measured serially over a 7-day period. The highest mean peak serum concentration was 2.06 micrograms/ml. Comparable peak values were seen 2 to 4 hours after administration of 22,000 IU of procaine penicillin G/kg of body weight given once or twice daily. A minimum serum concentration of 0.25 micrograms/ml was selected as adequate for efficacy against...
Semrad SD, Sams RA, Harris ON, Ashcraft SM.Flunixin meglumine and phenylbutazone are nonsteroidal anti-inflammatory drugs commonly used for the management of colic, endotoxemia, and musculoskeletal disorders in equids. Although it is not usually recommended, there appears to be an increasing trend to use nonsteroid anti-inflammatory drugs in combination to enhance or prolong their effects. Therefore, we studied the effect of concurrent administration of flunixin (1.1 mg/kg of body weight, IV) as flunixin meglumine and phenylbutazone (2.2 mg/kg, IV) on the pharmacokinetics of each drug and on in vitro thromboxane B2 production. Pharmaco...
Robinson NE, Derksen FJ, Berney C, Goossens L.The airway response to aerosol administration of the anticholinergic agent ipratropium bromide was determined in 8 horses with recurrent airway obstruction (heaves). The reversibility of airway obstruction was confirmed by measuring lung function before and during stabling; and by determining the response to atropine administration (0.02 mg/kg bwt intravenously). The dose-response to ipratropium bromide was determined using a Williams square design experiment in which 25, 50 or 75 micrograms ipratropium bromide/ml (4 ml/100 kg bwt) or the same volume of vehicle was administered to each horse b...
Sandersen CF, Detilleux J, Delguste C, Pierard L, van Loon G, Amory H.High-dose dobutamine stress echocardiography has been shown to be cardiotoxic and arrhythmogenic in horses. However, the test may have benefit in practice as a pharmacological challenge of exercise without the treadmill being required. Objective: To investigate the effect of low-dose dobutamine on cardiac performance in ponies previously treated with atropine, in order to develop a pharmacological protocol that allows examination of the equine heart under stimulation. Methods: In 13 healthy Shetland ponies, heart rate (HR), stroke index (SI) and cardiac index (CI) were calculated from pulsed-w...
Marti M, Mevissen M, Althaus H, Steiner A.The goal of this study was to investigate the effect of bethanechol (BeCh) on contractility patterns of smooth muscle preparations of equine duodenum descendens, jejunum, caecum and pelvic flexure in vitro. Concentration-response relationships were developed for BeCh using in vitro assays with and without preincubation of muscarinic (M) receptor antagonists for M2 and M3 receptors. BeCh induced a significant, concentration-dependent increase in contractile response in equine intestine in specimens with circular orientation. The maximal effect was largest for jejunal specimens with no differenc...
Lakritz J, Wilson WD, Mihalyi JE.To determine pharmacokinetics and bioavailability of erythromycin base after intragastric administration and erythromycin lactobionate after IV administration to healthy foals and to compare a microbiologic assay with a high-performance liquid chromatography (HPLC) method to determine plasma concentrations of erythromycin A. Methods: 6 healthy foals that were 2 to 4 months old. Methods: Foals were given single doses of erythromycin (10 mg/kg of body weight, IV, and 25 mg/kg, intragastrically) in a crossover study. Venous blood samples were obtained at specific times after drug administration, ...
Love DN, Rose RJ, Martin IC, Bailey M.Twelve geldings were used to evaluate serum levels of penicillin following the intravenous (iv) and intramuscular (im) injection of benzylpenicillin, im procaine penicillin and im fortified benzathine penicillin, at a variety of dose rates. Blood samples were collected up to 7 h after iv and im benzylpenicillin, up to benzathine penicillin. Results were analysed using an analysis of variance and regression analyses were used to calculate the time taken for the serum penicillin concentration to decline to 0.5 micrograms/ml. As a result of the experiments the following dosage regimes could be re...
Roger T, Ruckebusch Y.The contractile activity of the equine large intestine exhibited a biphasic response to feeding: enhancement of migrating complexes passing along the colon and an increase of 50% in cyclic variations in smooth muscle at intervals of 20 min on the left ventral colon for a period of 5 to 7 h postfeeding. The cholinergic agonist, bethanechol (50 micrograms/kg subcutaneously), induced both the migrating complexes and the cyclic variations at intervals of 10-15 min. In contrast, the intra-arterial infusion of PGF2 alpha (3 micrograms/kg/min) increased the contractile activity during infusion, but w...
Kamerling SG, Cravens WM, Bagwell CA.The effects of detomidine, a veterinary sedative analgesic, were studied in the horse. Novel objective techniques were employed to assess the analgesic and sedative potency of this compound. Intravenous doses of 0.010, 0.020 and 0.040 mg/kg were administered to eight adult Thoroughbred racehorses according to a double-blind crossover design. Analgesia was measured by determining the latency to onset of the skin twitch and hoof withdrawal reflexes following noxious thermal stimulation of the withers and fetlock, respectively. Sedation was assessed by quantifying spontaneous locomotor activity i...
Fadel C, Giorgi M.According to in vitro and in vivo investigations, firocoxib (FX), a second-generation coxib, is a highly selective COX-2 inhibitor in horses. With a COX-1/COX-2 IC50 ratio of 643 in horses, FX spares the COX-1 inhibitory effects. It is approved for the treatment of musculoskeletal problems and lameness in horses and dogs with osteoarthritis (OA). For the treatment of OA in horses, both an injectable formulation for IV administration at a dose of 0.09 mg/kg for five days and an oral paste formulation at a dose of 0.1 mg/kg for 14 days are licensed. Numerous analytical methods were reported in...
Belloli C, Carcano R, Arioli F, Beretta C.We used isolated equine digital arteries to study the vasodilatory mechanism of isoxsuprine, and fowl caecum preparations to investigate the affinity of the drug for beta-adrenoceptors. Isoxsuprine is a potent vasodilator of arterial smooth muscle that has been precontracted by an alpha-adrenoceptor agonist such as noradrenaline (log EC50 = -6.33 [-5.98; -6.68]). The present study indicates that its effect is due to alpha-adrenoceptor blockade since: (1) after a long lasting exposure to cumulative doses of isoxsuprine the vasoconstricting action of noradrenaline cannot be restored; (2) isoxsup...
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...
Robertson TP, Moore JN, Noschka E, Lewis TH, Lewis SJ, Peroni JF.To determine the effects of inhibition of Rho-kinase or Src-family protein tyrosine kinases (srcPTK) on agonist-induced contractile responses in equine laminar arteries and veins. Methods: Laminar arteries and veins obtained from 13 adult mixed-breed horses. Methods: Laminar vessels were mounted on myographs and exposed to phenylephrine (PE), 5-hydroxytryptamine (5-HT), prostaglandin F(2) (PGF(2)), and endothelin-1 (ET-1) with or without the Rho-kinase inhibitor Y-27632 (10 microM), srcPTK inhibitor PP2 (10 microM), or a negative control analogue for PP2 (PP3; 10 microM). Results: Responses to...
Haddad NS, Pedersoli WM, Ravis WR, Fazeli MH, Carson RL.Healthy mature pony mares (n = 6) were given a single dose of gentamicin (5 mg/kg of body weight) IV or IM 8 days apart. Venous blood samples were collected at 0, 5, 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, 30, 36, 40, and 48 hours after IV injection of gentamicin, and at 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, and 30 hours after IM injection of gentamicin. Gentamicin serum concentration was determined by a liquid-phase radioimmunoassay. The combined data of IV and IM treatments were analyzed by a nonlinear least-square...
Trachsel D, Tschudi P, Portier CJ, Kuhn M, Thormann W, Scholtysik G, Mevissen M.Atrial fibrillation is a well-known heart disease in horses. The common therapy consists of administration of quinidine. More potent antiarrhythmic drugs have become available for human therapy and the use of these as alternatives to quinidine for equine antiarrhythmic therapy is a matter of interest. Amiodarone (AMD) is used in human medicine for treatment of many arrhythmias, including atrial fibrillation. Its disposition in horses has not yet been investigated. The purpose of this study was to measure the effect of single intravenous doses of amiodarone (5 and 7 mg/kg) on the surface electr...
Alonso JM, Martins ES, Peccinini RG, Rosa GS, Guerra ST, Ribeiro MG, Santos B, García HDM, Watanabe MJ, Takahira RK, Rodrigues CA, Alves ALG....Intraperitoneal ceftriaxone administration in healthy horses results in high and prolonged peritoneal concentrations. Recent findings suggest that intraperitoneal ceftriaxone might increase survival rates in horses affected by peritonitis. The present study aimed to evaluate plasma and peritoneal concentrations of ceftriaxone after intraperitoneal administration in horses with septic peritonitis. Twenty-six horses presenting clinical, laboratorial, and sonographic findings compatible with the disease were included. All horses received daily intraperitoneal ceftriaxone (25 mg/kg bwt) in additi...
Young LE, Blissitt KJ, Clutton RE, Molony V.To evaluate temporal hemodynamic effects of dobutamine in horses anesthetized with halothane. Methods: 8 adult Thoroughbreds. Methods: Anesthesia was induced by i.v. administration of romifidine and ketamine and maintained using halothane in oxygen. After 60 minutes, dobutamine was administered i.v. for 60 minutes at 4 micrograms/kg of body weight/min. Measurements of left ventricular function were obtained by transesophageal echocardiography and cardiac catheterization. Results: Mean, systolic, diastolic, aortic, pulmonary arterial, and left and right ventricular end-diastolic and systolic pr...
Raidal SL, Edwards S.To determine the pharmacokinetics of potassium bromide (KBr) in horses after a single and multiple oral doses. Methods: Twelve adult Standardbred and Thoroughbred mares. Methods: Horses were randomly assigned into two treatment groups. In Part 1 of the study, horses were given a single oral dose of 120 mg/kg KBr. Part 2 of the study evaluated a loading dose of 120 mg/kg KBr daily by stomach tube for 5 days, followed by 40 mg/kg daily in feed for 7 days. Serum concentrations of bromide were determined by colorimetric spectrophotometry following drug administration to permit determination of con...
