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.
Durando MM, Slack J, Reef VB, Birks EK.There is interest in using pharmacological stress testing (PST) as a substitute for exercise stress testing (EST) to evaluate cardiac function in horses. Objective: To compare the effect of PST and EST on right ventricular pressure dynamics and stress echocardiography. Methods: Five horses completed a PST and EST in a randomised crossover design. High fidelity pressure transducers were placed in the right ventricle. Continuous pressure signals were digitally collected and stored, and dP/dtmax, dP/dtmin and tau calculated from these measurements. ECGs were recorded continuously for 20 h. Echoca...
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...
Villa R, Cagnardi P, Belloli C, Zonca A, Zizzadoro C, Ferro E, Carli S.The selective COX-2-inhibitor nimesulide is used extra-label in equine veterinary practice as an anti-inflammatory agent. However, there are no data on which to base the rational use of the drug in this species. Objective: To determine the effective COX selectivity of nimesulide in the horse, and suggest a suitable dosing schedule. Methods: The pharmacokinetics of nimesulide in the horse after oral administration (1 mg/kg bwt), and oral and i.v. administration (1.5 mg/kg bwt) were investigated, effects of feeding status on bioavailability determined, and plasma protein binding of the drug and ...
Schwarzwald CC, Hamlin RL, Bonagura JD, Nishijima Y, Meadows C, Carnes CA.Although atrial arrhythmias are clinically important in horses, atrial electrophysiology has been incompletely studied. Objective: Standard electrophysiologic methods can be used to study drug effects in horses. Specifically, the effects of diltiazem on atrioventricular (AV) nodal conduction are rate-dependent and allow control of ventricular response rate during rapid atrial pacing in horses undergoing quinidine treatment. Methods: Fourteen healthy horses. Methods: Arterial blood pressure, surface electrocardiogram, and right atrial electrogram were recorded during sinus rhythm and during pro...
Auer U, Uray C, Mosing M.To investigate the onset and duration of neuromuscular blockade of rocuronium bromide and its associated haemodynamic effects at three doses in healthy horses. Methods: Prospective, randomized experimental study. Methods: Seven adult horses aged 3-20 (mean 10.3) years and weighing 466 +/- 44 (mean +/- SD) kg. Methods: Horses were anaesthetized three times with at least 2 weeks between. They were pre-medicated with 0.6 mg kg(-1) xylazine and 0.01 mg kg(-1) butorphanol i.v.. Anaesthesia was induced with 2.2 mg kg(-1) ketamine and 0.1 mg kg(-1) diazepam i.v.. Following orotracheal intubation anae...
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...
Larenza MP, Landoni MF, Levionnois OL, Knobloch M, Kronen PW, Theurillat R, Schatzmann U, Thormann W.The arterial pharmacokinetics of ketamine and norketamine enantiomers after racemic ketamine or S-ketamine i.v. administration were evaluated in seven gelding ponies in a crossover study (2-month interval). Methods: Anaesthesia was induced with isoflurane in oxygen via a face-mask and then maintained at each pony's individual MAC. Racemic ketamine (2.2 mg kg(-1)) or S-ketamine (1.1 mg kg(-1)) was injected in the right jugular vein. Blood samples were collected from the right carotid artery before and at 1, 2, 4, 8, 16, 32, 64, and 128 min after ketamine administration. Ketamine and norketamine...
Cesarini C, Hamilton E, Picandet V, Lavoie JP.Theophylline has been shown to have corticosteroid-sparing effects for the treatment of human asthma. A similar effect, if present in horses, would allow diminishing the dose of corticosteroids administered to equine patients with inflammatory airway diseases. Objective: To evaluate whether theophylline potentiates the effects of a low dose of dexamethasone when treating horses with recurrent airway obstruction (RAO). Objective: Theophylline has steroid-sparing effects in horses with RAO. Methods: Ten mature mixed breed horses in clinical exacerbation of RAO were studied. Using an incomplete c...
Camargo FC, Robinson NE, Berney C, Eberhart S, Baker S, DeTolve P, Derksen FJ, Harkins JD, Lehner AF, Tobin T.Trimetoquinol (TMQ) is a potent beta-adrenoceptor agonist bronchodilator used in human medicine but has not been evaluated for potential use as a therapeutic agent for horses with 'heaves'. Objective: To assess the pharmacodynamics of TMQ in horses with 'heaves' to determine potential therapeutic effects. Methods: Increasing doses of TMQ were administered to horses with 'heaves' by i.v. and intratracheal (i.t.) routes. Doses ranged 0.001-0.2 microg/kg bwt i.v. and 0.01-2 microg/kg bwt i.t. Cardiac and airways effects were assessed by measurement of heart rate (HR) and maximal change in pleural...
Driessen B, Nann L, Benton R, Boston R.To study whether hemodynamic function in horses, particularly mean arterial blood pressure (MAP), is better maintained with sevoflurane than isoflurane, thus requiring less pharmacological support. Methods: Prospective randomized clinical investigation. Animals Thirty-nine racehorses undergoing arthroscopy in lateral recumbency. Methods: Horses were assigned to receive either isoflurane (n = 20) or sevoflurane (n = 19) at 0.9-1.0 minimum alveolar concentration (MAC) for maintenance of anesthesia. Besides routine clinical monitoring, cardiac output (CO) was measured by lithium dilution. Hemodyn...
Lankveld DP, Driessen B, Soma LR, Moate PJ, Rudy J, Uboh CE, van Dijk P, Hellebrekers LJ.Ketamine (KET) possesses analgesic and anti-inflammatory activity at sub-anesthetic doses, suggesting a benefit of long-term KET treatment in horses suffering from pain, inflammatory tissue injury and/or endotoxemia. However, data describing the pharmacodynamic effects and safety of constant rate infusion (CRI) of KET and its pharmacokinetic profile in nonpremedicated horses are missing. Therefore, we administered to six healthy horses a CRI of 1.5 mg/kg/h KET over 320 min following initial drug loading. Cardiopulmonary parameters, arterial blood gases, glucose, lactate, cortisol, insulin, non...
Parra-Sanchez A, Lugo J, Boothe DM, Gaughan EM, Hanson RR, Duran S, Belknap JK.To evaluate the pharmacokinetic-pharmacodynamic parameters of enrofloxacin and a low dose of amikacin administered via regional IV limb perfusion (RILP) in standing horses. Methods: 14 adult horses. Methods: Standing horses (7 horses/group) received either enrofloxacin (1.5 mg/kg) or amikacin (250 mg) via RILP (involving tourniquet application) in 1 forelimb. Samples of interstitial fluid (collected via implanted capillary ultrafiltration devices) from the bone marrow (BMIF) of the third metacarpal bone and overlying subcutaneous tissues (STIF), blood, and synovial fluid of the radiocarpal joi...
Womble AY, Giguère S, Lee EA, Vickroy TW.To determine pharmacokinetics of clarithromycin and concentrations in body fluids and bronchoalveolar (BAL) cells of foals. Methods: 6 healthy 2-to 3-week-old foals. Methods: In a crossover design, clarithromycin (7.5 mg/kg) was administered to each foal via IV and intragastric (IG) routes. After the initial IG administration, 5 additional doses were administered IG at 12-hour intervals. Concentrations of clarithromycin and its 14-hydroxy metabolite were measured in serum by use of high-performance liquid chromatography. A microbiologic assay was used to measure clarithromycin activity in seru...
Fielding CL, Brumbaugh GW, Matthews NS, Peck KE, Roussel AJ.To determine the pharmacokinetics and clinical effects of a subanesthetic, continuous rate infusion of ketamine administered to healthy awake horses. Methods: 8 adult horses. Methods: Ketamine hydrochloride was administered to 2 horses, in a pilot study, at rates ranging from 0.4 to 1.6 mg/kg/h for 6 hours to determine an appropriate dose that did not cause adverse effects. Ketamine was then administered to 6 horses for a total of 12 hours (3 horses at 0.4 mg/kg/h for 6 hours followed by 0.8 mg/kg/h for 6 hours and 3 horses at 0.8 mg/kg/h for 6 hours followed by 0.4 mg/kg/h for 6 hours). Conce...
Gehlen H, Groner U, Rohn K, Stadler P.In 18 horses, the pulmonary artery wedge pressure and the heart rate were measured during pharmacological stress load. 12 horses were healthy (4 trained, 8 untrained) and 6 horses had a heart disease (3 trained, 3 untrained). Pharmacological stress induction was carried out with the sympathomimetic drug dobutamine at a dosage rate of 7.5 microg/kg/min over 10 minutes of infusion. At the fourth minute, the parasympatholytic drug atropine was administered (5 microg/kg bw), and the heart rate and the pulmonary artery wedge pressure were continuously measured over 26 minutes. During sole dobutamin...
Dirikolu L, McFadden ET, Ely KJ, ElkHoly H, Lehner AF, Thompson K.Clonidine is classified as a class 3 performance-enhancing agent by the Association of Racing Commissioners International and thus has the potential to influence the outcome of a race. In this study, the authors developed and validated a sensitive gas chromatograph and mass spectrometer method to determine the pharmacokinetic parameters of clonidine in equine plasma samples after IV administration of a single dose (0.025 mg/kg) of clonidine in horses. At this dose, clonidine produced rapid and profound sedation, which cold be quickly reversed with yohimbine. Clonidine was able to produce an an...
Fernández-Varón E, Ayala I, Marín P, Carrión A, Martos N, Escudero E, Cárceles CM.Danofloxacin is a fluoroquinolone developed for veterinary medicine showing an excellent activity. However, danofloxacin pharmacokinetics profile have not been studied in horses previously. Objective: To study the pharmacokinetics following i.v., i.m. and intragastric (i.g.) administration of 1.25 mg/kg bwt danofloxacin to 6 healthy horses. Methods: A cross-over design was used in 3 phases (2 x 2 x 2), with 2 washout periods of 15 days (n = 6). Danofloxacin (18%) was administered by i.v. and i.m. routes at single doses of 1.25 mg/kg bwt. For i.g. administration an oral solution was prepared an...
Stokes AM, Venugopal CS, Hosgood G, Eades SC, Moore RM.The goals of this study were to determine the concentration-response (C-R) relationship of endothelin-1 (ET-1), compare 2 ET-receptor antagonists and determine the antagonist concentrations that block the vasomotor effects of ET-1, and compare the effectiveness of ET-1 and previously studied vasoconstrictors in equine palmar digital arterial and venous rings in vitro. Vessel rings from 8 nonlaminitic horses were placed in Tyrode's solution, 1 side fixed to the floor of an organ bath and the other side fixed to a force-displacement transducer. Two separate studies were conducted: (I) incubation...
Brandon CI, Vandenplas M, Dookwah H, Linden J, Murray TF.The aim of the current study was to clone the equine adenosine A(2A) receptor gene and to establish a heterologous expression system to ascertain its pharmacologic profile via radioligand binding and functional assays. An eA(2A)-R expression construct was generated by ligation of the eA(2A) cDNA into the pcDNA3.1 expression vector, and stably transfected into human embryonic kidney cells (HEK). Binding assays identified those clones expressing the eA(2A)-R, and equilibrium saturation isotherm experiments were utilized to determine dissociation constants (K(D)), and receptor densities (B(max)) ...
Knobloch M, Portier CJ, Levionnois OL, Theurillat R, Thormann W, Spadavecchia C, Mevissen M.Ketamine is widely used as an anesthetic in a variety of drug combinations in human and veterinary medicine. Recently, it gained new interest for use in long-term pain therapy administered in sub-anesthetic doses in humans and animals. The purpose of this study was to develop a physiologically based pharmacokinetic (PBPk) model for ketamine in ponies and to investigate the effect of low-dose ketamine infusion on the amplitude and the duration of the nociceptive withdrawal reflex (NWR). A target-controlled infusion (TCI) of ketamine with a target plasma level of 1 microg/ml S-ketamine over 120 ...
Gokbulut C, Akar F, McKellar QA.Fenbendazole (FBZ), oxfendazole (fenbendazole sulphoxide, FBZSO), and albendazole (ABZ) were administered orally to donkeys at 10mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment. The plasma and faecal samples were analysed by high performance liquid chromatography (HPLC). The parent molecule and its sulphoxide and sulphone (FBZSO(2)) metabolites did not reach detectable concentrations in any plasma samples following FBZ administration. ABZ was also not detected in any plasma samples, but its sulphoxide and sulphone metabolites were detected, demonstratin...
Bousquet-Mélou A, Formentini E, Picard-Hagen N, Delage L, Laroute V, Toutain PL.The present study aimed to characterize the adrenal response to ACTH. A model was developed that coupled the nonlinear disposition of cortisol with a physiologically based model for cortisol secretion by the adrenals. It was assumed that the response to ACTH resulted from two mechanisms: a stimulation of the cortisol secretion rate and control of the duration of the secretion. Seven dose levels of ACTH were tested in horses, a species similar to man as regards adrenal function. The main result was that the secretion rate of the adrenal gland can be modelized by a zero order process that is max...
Fernández-Varón E, Cárceles CM, Marín P, Martos N, Escudero E, Ayala I.To study the pharmacokinetics of difloxacin (5 mg/kg) following IV, IM, and intragastric (IG) administration to healthy horses. Methods: 6 healthy mature horses. Methods: A crossover study design with 3 phases was used (15-day washout periods between treatments). An injectable formulation of difloxacin (5%) was administered IV and IM in single doses (5 mg/kg); for IG administration, an oral solution was prepared and administered via nasogastric tube. Blood samples were collected before and at intervals after each administration. A high-performance liquid chromatography assay with fluorescence ...
Sinclair MD, Mealey KL, Matthews NS, Peck KE, Taylor TS, Bennett BS.To determine the disposition of a bolus of meloxicam (administered IV) in horses and donkeys (Equus asinus) and compare the relative pharmacokinetic variables between the species. Methods: 5 clinically normal horses and 5 clinically normal donkeys. Methods: Blood samples were collected before and after IV administration of a bolus of meloxicam (0.6 mg/kg). Serum meloxicam concentrations were determined in triplicate via high-performance liquid chromatography. The serum concentration-time curve for each horse and donkey was analyzed separately to estimate standard noncompartmental pharmacokinet...
Boscan P, Van Hoogmoed LM, Pypendop BH, Farver TB, Snyder JR.To determine the pharmacokinetics and effects of the morphine antagonist N-methylnaltrexone (MNTX) on gastrointestinal tract function in horses when administered alone and in combination with morphine. Methods: 5 healthy adult horses. Methods: Horses were treated with MNTX (1 mg/kg, IV), and serial blood samples were collected for determination of drug pharmacokinetics. For evaluation of effects on the gastrointestinal tract when administered alone, MNTX was administered at a dosage of 0.75 mg/kg, IV, twice daily for 4 days. For evaluation of effects when administered concurrently with morphin...
Davis JL, Salmon JH, Papich MG.To characterize pharmacokinetics of voriconazole in horses after oral and IV administration and determine the in vitro physicochemical characteristics of the drug that may affect oral absorption and tissue distribution. Methods: 6 adult horses. Methods: Horses were administered voriconazole (1 mg/kg, IV, or 4 mg/kg, PO), and plasma concentrations were measured by use of high-performance liquid chromatography. In vitro plasma protein binding and the octanol:water partition coefficient were also assessed. Results: Voriconazole was adequately absorbed after oral administration in horses, with a s...
Davis JL, Papich MG, Weingarten A.The purpose of this study was to determine the pharmacokinetics and physicochemical characteristics of orbifloxacin in the horse. Six healthy adult horses were administered oral and intravenous orbifloxacin at a dose of 2.5 mg/kg. Plasma samples were collected and analyzed by high-pressure liquid chromatography with ultraviolet detection. Plasma protein binding and lipophilicity were determined in vitro. Following i.v. administration, orbifloxacin had a terminal half-life (t1/2) of 5.08 h and a volume of distribution (V(d(SS))) of 1.58 L/kg. Following oral administration, the average maximum p...
Maes A, Baert K, Croubels S, De Clercq D, van Loon G, Deprez P, De Backer P.A rapid method for the quantification of amiodarone and desethylamiodarone in animal plasma using high-performance liquid chromatography combined with UV detection (HPLC-UV) is presented. The sample preparation includes a simple deproteinisation step with acetonitrile. In addition, a sensitive method for the quantification of amiodarone and desethylamiodarone in horse plasma and urine using high-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) is described. The sample preparation includes a solid-phase extraction (SPE) with a SCX c...
Soma LR, Uboh CE, Luo Y, Guan F, Moate PJ, Boston RC.To determine the pharmacokinetics of methylprednisolone (MP) and develop a pharmacokinetic-pharmacodynamic model of the related changes in plasma concentrations of endogenous hydrocortisone (HYD) and cortisone (COR) following intra-articular administration of methylprednisolone acetate (MPA) in horses. Methods: 6 Thoroughbreds. Methods: In each horse, 200 mg of MPA was injected intrasynovially into a carpal joint, and plasma MP, HYD, and COR concentrations were determined via liquid chromatography-mass spectrometry. Results: A 5-compartment pharmacokinetic-pharmacodynamic model was used to des...
Olsén L, Ingvast-Larsson C, Larsson P, Broström H, Bondesson U, Sundqvist M, Tjälve H.The pharmacokinetics and the effects on inhibition of histamine-induced cutaneous wheal formation of the histamine H1-antagonist fexofenadine were studied in horse. The effect of ivermectin pretreatment on the pharmacokinetics of fexofenadine was also examined. After intravenous infusion of fexofenadine at 0.7 mg/kg bw the mean terminal half-life was 2.4 h (range: 2.0-2.7 h), the apparent volume of distribution 0.8 L/kg (0.5-0.9 L/kg), and the total body clearance 0.8 L/h/kg (0.6-1.2 L/h/kg). After oral administration of fexofenadine at 10 mg/kg bw bioavailability was 2.6% (1.9-2.9%). Ivermect...
Stokes AM, Venugopal CS, Hosgood G, Eades SC, Moore RM.The goals of this study were to determine the concentration-response (C-R) relationship of endothelin-1 (ET-1), compare 2 ET-receptor antagonists and determine the antagonist concentrations that block the vasomotor effects of ET-1, and compare the effectiveness of ET-1 and previously studied vasoconstrictors in equine palmar digital arterial and venous rings in vitro. Vessel rings from 8 nonlaminitic horses were placed in Tyrode's solution, 1 side fixed to the floor of an organ bath and the other side fixed to a force-displacement transducer. Two separate studies were conducted: (I) incubation...
Kerr DD, Jones EW, Holbert D, Huggins K.A 3-way Latin square design was used to compare the sedative and preanesthetic effects of xylazine given intravenously (i.v.) (1.1 mg./kg.) and given intramuscularly (i.m.) (2.2 mg./kg.) and acetylpromazine maleate (0.66 mg./kg.) given i.v. in the horse. Physiologic responses were recorded and clinical observations were made. Intravenous administration of xylazine and atropine sulphate (0.011 mg./kg.) appeared to have superior sedative properties, without having adverse effects on cardiovascular and respiratory systems. Both the i.v. and the i.m. administrations of xylazine prior to induction ...
Caprile KA, Short CR.Rational drug therapy in the foal requires a sound knowledge of the pharmacodynamics and pharmacokinetics of various drugs as well as a thorough understanding of the physiologic differences that exist between the neonate and the adult and that may serve to alter drug disposition and, therefore, drug response. A summary of these physiologic factors with emphasis on the foal is presented and is followed by recommendations regarding the applied therapeutics of various antimicrobial agents.
Thomas AD, Bowater IC, Vine JH, McLean JG.To determine whether a drug detected in the blood or urine of a racing animal could have penetrated through the skin from a topically applied preparation. Methods: Blood and urine of dogs and horses were analysed after topical administration of three common nonsteroidal anti-inflammatory preparations. Methods: Dimethylsulphoxide was analysed using a gas chromatograph with a flame photometric detector. Phenylbutazone, its metabolites and lignocaine were analysed using a gas chromatograph with a mass selective detector. Results: Dimethylsulphoxide, phenylbutazone and lignocaine were detected in ...
Alvarez AV, Schumacher J, DeGraves FJ.OBJECTIVE To determine whether addition of epinephrine to a lidocaine solution would prolong and potentiate the efficacy of a palmar digital nerve block (PDNB) in horses. ANIMALS 6 adult horses with naturally occurring forefoot lameness. PROCEDURES Initially, a PDNB with a 2% lidocaine solution was performed on the affected foot of each horse. Three days later, the PDNB was repeated with a 1% lidocaine solution or a 1% lidocaine solution containing epinephrine (dilution, 1:200,000). After another 3-day washout period, the PDNB was repeated with the treatment opposite that administered for the ...
Hunter RP, Short CR, McClure JR, Koch CE, Keowen ML, VanSteenhouse JL, Dees AA.Cimetidine (CIM) is an H2-receptor antagonist that has been used in racehorses in an attempt to reduce the occurrence of stress-related gastric ulceration. It has also been shown to produce several useful effects other than its gastric acid suppression properties. Further, it is a well documented antagonist of cytochrome P-450 (CYP) mediated oxygenation reactions. Nitric oxide (NO), a recently discovered mediator or modifier of numerous physiological functions, is generated by several forms of nitric oxide synthase (NOS), one of which is inducible (iNOS). Inducible NOS, expressed in neutrophil...
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...
Schatzmann U, Gugelmann M, Von Cranach J, Ludwig BM, Rehm WF.Carprofen, flunixin meglumine and placebo in the form of a physiological solution of sodium chloride were tested in an open randomised cross-over trial for analgesic efficacy in horses with two external skin-stimulation systems. Both systems, the withers model and the "heating element" model, were compared in order to find an optimal way to measure pain perception after stimulating the skin with high temperature. No analgesic effect of flunixin or carprofen could be demonstrated when using the withers model. In the "heating element" model, a 1.1 mg/kg i.v. dose of flunixin meglumine failed to ...
Wagner AE, Mama KR, Contino EK, Ferris DJ, Kawcak CE.To evaluate the sedative and analgesic effects of subanesthetic doses of ketamine in horses sedated with xylazine, with or without butorphanol. Methods: Prospective, randomized, controlled study. Methods: 10 adult horses. Methods: Each horse was sedated multiple times by administration of xylazine (treatment X), xylazine and butorphanol (treatment XB), xylazine with 1 of 2 dosages of ketamine (treatment XK1 or XK2), or xylazine and butorphanol with 1 of 2 dosages of ketamine (treatment XBK1 or XBK2). Head height and various behaviors, including responses to noise, insertion of a dental float, ...
Pozzoli C, Bertini S, Poli E, Placenza G, Menozzi A.β-adrenoceptor agonists are considered the most effective drugs to counteract bronchoconstriction in horses with asthma, but only clenbuterol is commonly employed in clinical practice. We evaluated the effects of different selective β agonists: clenbuterol, ritodrine, salbutamol, and fenoterol on the contractions of isolated bronchial muscle of horses induced by electrical field stimulation (EFS), carbachol, histamine, and KCl. All β agonists reduced the amplitude of contraction induced by the different stimuli but with variable efficacy and potency. Fenoterol and salbutamol were more effec...
Herholz C, Straub R, Busato A.Several indices of ventilatory heterogeneity can be identified from the volumetric capnogram and its graphic presentation, the single-breath diagram for CO2 (SBD-CO2). Physiologically based indices of pulmonary function (VTE, VCO2, FACO2, VDBohr% VDBohr%, VD/VTE, A1/A2) were calculated for healthy horses (group I, n = 5) and for horses with subclinical (group II, n = 7) or clinically manifest chronic obstructive pulmonary disease (COPD) (group III, n = 8) during tidal breathing and after medication with lobelin hydrochloride (Lobelin). We investigated the variability and repeatability of the l...
Swanson CR, Muir WW.The influence of positive end-expiratory pressure (PEEP) on the alveolar-arterial O2 tension difference [P(A-a)O2], physiologic right-to-left shunt fraction, physiologic dead space-to-tidal volume ratio, and hemodynamic variables was studied in halothane-anesthetized horses maintained in dorsal recumbency during controlled ventilation. Dobutamine was used to minimize the adverse cardiovascular consequences of PEEP. Six adult horses were anesthetized, using xylazine (2.2 mg/kg of body weight, IM), guaifenesin (50 mg/kg, IV), thiamylal Na (4.4 mg/kg, IV), and halothane (1.5 to 2% inspired) in 10...
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(...
Sandersen C, Mouithys-Mickalad A, de la Rebière G, Deby G, Serteyn D, Franck T.To investigate the effect of acepromazine (ACP) on reactive oxygen species (ROS) production by stimulated equine neutrophils. Methods: Ex vivo biochemical experiments. Methods: Isolated neutrophils from healthy untreated horses. Methods: Neutrophils were incubated with ACP at concentrations of 10(-4), 10(-5) or 10(-6) M and then stimulated with phorbol-myristate-acetate (PMA) before measurement of lucigenin-enhanced chemiluminescence (CL). In a second experiment neutrophils were incubated in the presence of α-keto-γ methylthiobutyric acid (KMB) and treated with ACP at concentrations of 10(-4...
Shane SE, Langston VC, Wills RW, Denney WS, Knych H, Fontenot RL, Meyer RE, Natalini CC.An ideal dexmedetomidine protocol has yet to be determined for standing sedation in horses. It was hypothesized that an IV bolus followed by CRI dexmedetomidine would have a quicker increase in plasma concentrations compared with repeated IM injections. In a crossover design, eight adult, female horses were randomly placed into two groups: the CRI group (IV bolus dexmedetomidine at 0.005 mg/kg followed by a CRI at 0.01 mg/kg/h for 15 min then 0.005 mg/kg/h for 60 min) and the IM group (dexmedetomidine at 0.01 mg/kg, followed by 0.005 mg/kg in 30-min intervals for 60 min). Clearance and...
De Clercq D, Baert K, Croubels S, van Loon G, Maes A, Tavernier R, Deprez P, De Backer P.To determine the clinical effects and pharmacokinetics of amiodarone after single doses of 5 mg/kg administered orally or intravenously. Methods: 6 healthy adult horses. Methods: In a cross over study, clinical signs and electrocardiographic variables were monitored and plasma and urine samples were collected. A liquid chromatography-mass spectrometry method was used to determine the percentage of protein binding and to measure plasma and urine concentrations of amiodarone and the active metabolite desethylamiodarone. Results: No adverse clinical signs were observed. After IV administration, m...
Nolan AM, Hall LW.The effects of four intravenous combinations, xylazine (0.7 mg/kg)/methadone (0.1 mg/kg), xylazine (0.7 mg/kg)/buprenorphine (0.004 and 0.006 mg/kg) and acepromazine (0.05 mg/kg)/buprenorphine (0.006 mg/kg) on arterial blood pressure, central venous pressure, heart rate, respiratory rate and blood gases were studied in four experimental ponies. With xylazine/buprenorphine and xylazine/methadone onset of sedation was rapid and obvious and although no surgical or diagnostic procedures were carried out, sedation was judged to be satisfactory for the next 30 to 40 minutes. Onset of sedation after ...
Hardee MM, Moore JN, Hardee GE.The efficacy of three agents which alter the metabolism of arachidonic acid was investigated in normal, conscious horses. A dose response evaluation was made of flunixin meglumine and phenylbutazone, two cyclo-oxygenase inhibitors, and of a selective thromboxane synthetase inhibitor, UK-38,485. Radioimmunoassay of thromboxane B2 (TxB2) and 6-keto prostaglandin F1 alpha (PGF1 alpha) was used to assess the concentrations of thromboxane A2 (TxA2) and prostacyclin (PGI2) respectively, in serum. Flunixin was the most potent inhibitor of serum TxB2 and 6-keto PGF1 alpha production. UK-38,485 also de...
Serrano-Rodríguez JM, Gómez-Díez M, Esgueva M, Castejón-Riber C, Mena-Bravo A, Priego-Capote F, Ayala N, Caballero JMS, Muñoz A.Pharmacokinetic and pharmacodynamic (PK/PD) properties of the angiotensin-converting enzyme inhibitor (ACEI) benazeprilat have not been evaluated in horses. This study was designed to establish PK profiles for benazepril and benazeprilat after intravenous (IV) and oral (PO) administration of benazepril using a PK/PD model. This study also aims to determine the effects of benazeprilat on serum angiotensin converting enzyme (ACE), selecting the most appropriate dose that suppresses ACE activity. Six healthy horses in a crossover design received IV benazepril at 0.50mg/kg and PO at doses 0 (place...
Muir WW, McGuirk S.Knowledge of the dosage, rate and route of administration, and potential side effects of drugs used to treat cardiac disease in horses has been refined. The judicious use of these drugs can increase exercise capacity, improve health, and potentially prolong life. Currently, antiarrhythmics (quinidine, lidocaine), positive inotropies (digoxin), and diuretics (furosemide) are the primary agents used to treat cardiovascular disease in horses. The development of newer drugs (verapamil, milrinone, bumetanide) and their usefulness in therapy for horses with cardiovascular disease require further inv...
Schumacher SA, Toribio RE, Scansen B, Lakritz J, Bertone AL.The objectives of this study were to describe pharmacokinetic and pharmacodynamic changes as a result of a single intravenous administration of magnesium sulfate (MgSO ) to healthy horses. MgSO is a magnesium salt that has been used to calm horses in equestrian competition and is difficult to regulate because magnesium is an essential constituent of all mammals. Six healthy adult female horses were administered a single intravenous dose of MgSO at 60 mg/kg of body weight over 5 min. Blood, urine, and cerebrospinal fluid (CSF) samples were collected, and cardiovascular parameters were monitor...
Kuroda T, Nagata S, Takizawa Y, Tamura N, Kusano K, Mizobe F, Hariu K.The pharmacokinetics of d-chlorpheniramine (CPM), a histamine H1-receptor antagonist, and its ability to inhibit of histamine-induced cutaneous wheal formation, were studied in healthy Thoroughbred horses (n=5). Following an intravenous (IV) dose of 0.5mg/kg bodyweight (BW), plasma drug disposition was very rapid, with the mean terminal half-life and total body clearance calculated as 2.7h and 0.7 L/h/kg, respectively. The observed maximal inhibition of wheal formation following IV doses of 0.1 and 0.5mg/kg BW were 37.8% and 60.6% at 0.5h, respectively. Oral administration of CPM (0.5mg/kg BW)...
Habershon-Butcher J, Cutler C, Viljanto M, Hincks PR, Biddle S, Paine SW.Xylazine is widely used worldwide as a short-acting sedative in general equine and racing practice. In the UK, although it has a legitimate use during training, equine anti-doping rules state it is a prohibited substance on race day. The aim of the study was to produce a detection time (DT) to better inform European veterinary surgeons so that xylazine can be used appropriately under regulatory rules. Previous publications have various limitations pertaining to analysis method, particularly for plasma and limited length of time of sample collection. In this study, pharmacokinetic data were pro...
Martín-Jiménez T, Papich MG, Riviere JE.To develop and validate a population pharmacokinetic model for gentamicin in horses, using retrospective clinical data. Methods: 62 horses that had been treated IV with multiple doses of gentamicin at our veterinary teaching hospital between 1987 and 1996. Procedure-46 horses were assigned to the study group, and 16 to the validation group. Detailed history of dosage, sample collection times, and selected pathophysiologic variables were recorded for each patient. Samples were analyzed by use of a fluorescence polarization immunoassay method. Pharmacostatistical analysis was conducted, using co...
The ultra long-acting β -adrenoceptor agonist olodaterol plus the ultra long-acting muscarinic antagonist tiotropium bromide are known to relax equine airways. In human bronchi combining these drugs elicits a positive interaction, thus we aimed to characterize this information further in equine isolated airways stimulated by electrical field stimulation (EFS) and using the Concentration-Reduction Index (CRI) and Combination Index (CI) equations. The drugs were administered alone and together by reproducing ex vivo the concentration-ratio delivered by the currently available fixed-dose combina...
Peck KE, Matthews NS, Taylor TS, Mealey KL.To compare serum disposition of sulfamethoxazole and trimethoprim after IV administration to donkeys, mules, and horses. Methods: 5 donkeys, 5 mules, and 3 horses. Methods: Blood samples were collected before (time 0) and 5, 15, 30, and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 24 hours after IV administration of sulfamethoxazole (12.5 mg/kg) and trimethoprim (2.5 mg/kg). Serum was analyzed in triplicate with high-performance liquid chromatography for determination of sulfamethoxazole and trimethoprim concentrations. Serum concentration-time curve for each ani...
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 ...
Gustafsson K, Tatz AJ, Dahan R, Abu Ahmad W, Britzi M, Sutton GA, Kelmer G.The aim of this study was to investigate the safety and pharmacokinetics of trimethoprim-sulphadiazine administered via intravenous regional limb perfusion (IVRLP) into the cephalic vein. According to the hypothesis, the drug could be administered without adverse effects and the synovial concentrations would remain above the minimum inhibitory concentration (MIC) for trimethoprim-sulphadiazine (0.5 and 9.5 µg/mL) for 24 h. Ten ( = 10) horses underwent cephalic vein IVRLP with an Esmarch tourniquet applied for 30 min. Four grams (4 g) of trimethoprim-sulphadiazine (TMP-SDZ) were diluted at 0.9...
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...
Raidal SL, Burnheim K, Evans D, Hughes KJ.Sedation is often required to perform pulmonary function testing (PFT) in horses, but drug effects may influence respiratory function. The current study was designed to characterise the effects of sedation and bronchodilator administration on absolute and relative indices of pulmonary function during eupnoeic respiration and carbon dioxide-induced hyperpnoea (rebreathing) in healthy horses using a pneumotachographic spirometry system. Sedation with acetylpromazine (ACP), xylazine, or both drugs in combination was associated with significant reductions in respiratory frequency, minute ventilati...
