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.
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...
Campbell NB, Jones SL, Blikslager AT.A potential adverse effect of cyclo-oxygenase (COX) inhibitors (nonsteroidal anti-inflammatory drugs [NSAIDs]) in horses is colitis. In addition, we have previously shown an important role for COX-produced prostanoids in recovery of ischaemic-injured equine jejunum. It was hypothesised that the nonselective COX inhibitor flunixin would retard repair of bile-injured colon by preventing production of reparative prostaglandins, whereas the selective COX-2 inhibitor, etodolac would not inhibit repair as a result of continued COX-1 activity. Segments of the pelvic flexure were exposed to 1.5 mmol/l...
Belloli C, Crescenzo G, Lai O, Carofiglio V, Marang O, Ormas P.The objective of this study was to determine the pharmacokinetic behaviour of imidocarb in horses following a single i.m. injection at the dose commonly administered to treat Babesia caballi infections or to prevent babesiosis. Eight horses were injected i.m. with a single dose of 2.4 mg imidocarb dipropionate/kg bwt and blood, faecal, urine and milk samples were collected. For imidocarb determination, a high-performance liquid chromatographic method (HPLC) was used after weak cation-exchange solid phase, or liquid-liquid, extraction procedures. Twelve hours after treatment, no detectable plas...
van Duijkeren E, Ensink JM, Meijer LA.The distribution of trimethoprim (TMP) and sulfadiazine (SDZ) into subcutaneously implanted noninfected tissue chambers was studied in healthy adult ponies. Six ponies were given an oral TMP/SDZ paste formulation at a dose of 5 mg/kg TMP and 25 mg/kg SDZ at 12 h intervals for 2 days in order to reach steady-state concentrations. Plasma concentrations and tissue chamber fluid (TCF) concentrations of both drugs were measured at regular intervals during a period commencing 24 h after the last oral administration. The peak concentration of TMP (mean +/- SD) was 2.92 +/- 0.86 microg/mL for plasma a...
Bousquet-Melou A, Bernard S, Schneider M, Toutain PL.Marbofloxacin is a fluoroquinolone antibiotic expected to be effective in the treatment of infections involving gram-negative and some gram-positive bacteria in horses. In order to design a rational dosage regimen for the substance in horses, the pharmacokinetic properties of marbofloxacin were investigated in 6 horses after i.v., subcutaneous and oral administration of a single dose of 2 mg/kg bwt and the minimal inhibitory concentrations (MIC) assessed for bacteria isolated from equine infectious pathologies. The clearance of marbofloxacin was mean +/- s.d. 0.25 +/- 0.05 l/kg/h and the termi...
Carretero M, Rodríguez C, San Andrés MI, Forés P, de Lucas JJ, Nieto J, Waxman S, San Andrés MD, González F.The pharmacokinetic behaviour of marbofloxacin, a new fluoroquinolone antimicrobial agent developed exclusively for veterinary use, was studied in mature horses (n = 5) after single-dose i.v. and i.m. administrations of 2 mg/kg bwt. Drug concentrations in plasma were determined by high performance liquid chromatography (HPLC) and data obtained were subjected to compartmental and noncompartmental kinetic analysis. This compound presents a relatively high volume of distribution (V(SS) = 1.17 +/- 0.18 l/kg), which suggests good tissue penetration, and a total body clearance (Cl) of 0.19 +/- 0.042...
Toutain PL, Lassourd V.The current performance of analytical techniques used for drug control in horses lead the Regulatory Authorities to decide whether trace levels of drugs legitimately used for therapeutic medication should or should not be reported. Here, we propose a well-ordered and nonexperimental pharmacokinetic/pharmacodynamic approach for the determination of irrelevant drug plasma (IPC) and urine concentrations (IUC). The published plasma clearance is used to transform an effective (marketed) dose into an effective concentration (EPC). EPC is transformed into an IPC by applying a safety factor (SF). This...
Peroni DL, Stanley S, Kollias-Baker C, Robinson NE.Based on its efficacy for the treatment of human asthma, the corticosteroid prednisone is commonly used in horses for treatment of recurrent airway obstruction. However, recent studies have failed to show any benefit of prednisone tablets for the treatment of this condition. The purpose of this study was to determine why oral prednisone has poor efficacy for the treatment of heaves in horses. In a crossover study, 5 horses were given the following treatments: prednisone tablets, prednisone liquid, prednisolone tablets, prednisolone liquid and i.v. prednisolone sodium succinate (positive contro...
Lakritz J, Wilson WD, Marsh AE, Mihalyi JE.Plasma concentrations and pharmacokinetics of erythromycin and related compounds were determined after administration of erythromycin ethylsuccinate to six healthy male foals 3 to 5 months of age. Hay was withheld from the foals overnight and erythromycin ethylsuccinate (25 mg/kg of body weight) was administered intragastrically. Plasma erythromycin concentrations were determined at specific times after drug administration by high-performance liquid chromatography assay. Maximum peak plasma concentrations, time to maximum concentrations, area under plasma concentration versus time curves, elim...
Chilcoat CD, Rowlingson KA, Jones SL.Toxic products such as reactive oxygen intermediates released by activated polymorphonuclear neutrophil (PMN) have an important role in the pathophysiology of diseases associated with the deposition of immune complexes (IC) in tissues. IC-induced activation of PMN requires adhesion mediated by integrin adhesion receptors. Of the integrins expressed on PMN, the beta(2) family has been found to be of particular importance for activation of PMN by IC. beta(2) Integrin ligand binding must be activated to enable adhesion to IC. Both activating and inhibitory signals regulate beta(2) integrin ligand...
Daunt DA, Steffey EP.Administration of alpha-2 agonists to horses produces a variety of behavioral effects (sedation, somnolence, analgesia), and physiological effects. One of the most significant beneficial effects of administering alpha-2 agonists is the degree of analgesia they provide. Alpha-2 agonists have been the mainstay of analgesia for colic pain in horses since their introduction to clinical veterinary medicine. The increased potency of the more recently introduced alpha-2 agonists allows the provision of analgesia for conditions not previously relieved by other drugs. Unfortunately, there are significa...
Steffey EP.Both desflurane and sevoflurane offer theoretical and practical advantages over other inhalation anesthetics for horses. The lower solubility of both agents provides improved control of delivery and helps to counteract the confounding influence of the voluminous patient breathing circuit commonly used for anesthetizing horses. The lower solubility should account for faster rates of recovery compared with the older agents; whether or not the quality of recovery differs remains to be objectively evaluated in a broad range of circumstances. The pharmacodynamic effects are, in large part, similar ...
Hoff TK, Hood DM, Wagner IP.To evaluate the clinical efficacy of topically administered glyceryl trinitrate (GTN) for inducing digital submural vasodilation in clinically normal horses. Methods: 7 adult horses without foot abnormalities. Methods: A concurrent-control crossover design was used to determine whether topical application of GTN ointment for prevention or treatment of laminitis would result in a detectable increase in digital perfusion. Heat-acclimated horses instumented for detection of wall surface temperature (HWST), mean systemic pressure, and heart rate were used. Horses were exposed to cold to induce dig...
Knoll U, Strauhs P, Schusser G, Ungemach FR.Olsalazine sodium (Dipentum*) has been used therapeutically against inflammatory bowel disease in human medicine as an alternative to sulphasalazine over the past 20 years. Bacteria in the colon split this prodrug into two molecules of the locally effective 5-aminosalicylic acid (5-ASA). Considering the potential therapeutic use in equine colitis, the pharmacokinetics of olsalazine (OLZ) after single oral administration to six horses at a dosage of 30 mg/kg was investigated. Plasma concentrations of OLZ, 5-ASA, and its main metabolite N-acetyl-5-aminosalicylic acid (Ac-5-ASA) were analysed by ...
Martínez AC, Prieto D, Hernández M, García-Sacristán A, Benedito S.The present investigation was designed to evaluate the effect of histamine on isolated rings of horse deep dorsal penile vein. Under precontracted or basal conditions, histamine evoked an endothelium-independent contraction. Preincubation of the vein rings with the selective H1 receptor antagonist, mepyramine, shifted the concentration-response curve for histamine and to the H1 receptor agonist 2-pyridylethylamine to the right in a competitive manner. Pretreatment with cimetidine, a specific H2 receptor antagonist, did not modify the pEC50 and maximal contraction of the histamine response. Cim...
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...
Scheuch BC, Van Hoogmoed LM, Wilson WD, Snyder JR, MacDonald MH, Watson ZE, Steffey EP.To establish the route of infusion (IV or intraosseous) that results in the highest concentration of amikacin in the synovial fluid of the tibiotarsal joint and determine the duration of peak concentrations. Methods: 21 horses. Methods: Regional perfusion of a limb on 15 horses was performed. Amikacin sulfate was infused into the saphenous vein or via intraosseous infusion into the distal portion of the tibia (1 g in 56 ml of lactated Ringer's solution) or proximal portion of the metatarsus (1 g of amikacin in 26 ml of lactated Ringer's solution). Amikacin concentrations were measured in seque...
Gehring R.The Veterinary Pharmacovigilance Centre received 59 reports of suspected adverse drug reactions during the period January 1998 - February 2001. The number of reports received increased after the establishment of a formal procedure for recording and responding to reports. The number of reports received per species was: dogs 19, cats 15, cattle 7, sheep/ goats 6, chickens 4, pigs 3, horses 2 and giraffe 1. Many different types of adverse reactions were reported, including lack of efficacy, hypersensitivity, inappropriate use of products by non-veterinarians, known adverse effects and adverse eff...
Ohmura H, Hiraga A, Aida H, Kuwahara M, Tsubone H.To investigate the effects of repeated atropine injection on heart rate (HR) variability in resting Thoroughbred horses, two microg/ kg of atropine as parasympathetic nervous blockade was injected intravenously every 6 min to a total of 8 microg/kg after intravenous administration of 0.2 mg/kg of propranolol as sympathetic nervous blockade. We recorded electrocardiograms and obtained the HR, then evaluated variation in HR from the power spectrum in terms of low frequency (LF, 0.01-0.07 Hz) power and high frequency (HF, 0.07-0.6 Hz) power. Administration of atropine decreased parasympathetic ne...
Hatfield CL, McDonell WN, Lemke KA, Black WD.To determine the pharmacokinetics and toxic effects associated with IV administration of lithium chloride (LiCl) to conscious healthy horses. Methods: 6 healthy Standardbred horses. Methods: Twenty 3-mmol boluses of LiCl (0.15 mmol/L) were injected IV at 3-minute intervals (total dose, 60 mmol) during a 1-hour period. Blood samples for measurement of serum lithium concentrations were collected before injection and up to 24 hours after injection. Behavioral and systemic toxic effects of LiCl were also assessed. Results: Lithium elimination could best be described by a 3-compartment model for 5 ...
Chu KK, Cohen ND, Stanley SD, Wang N.To estimate the probability of concurrently exceeding thresholds for plasma concentration of furosemide and urine specific gravity after IV administration of furosemide in horses. Methods: 12 mature healthy Thoroughbred (n = 6) or Quarter Horse (6) mares. Methods: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after IV administration of 250 mg (first experiment) or 500 mg (second experiment) of furosemide. Urine was collected hourly between 1 and 6 hours after administration of furosemide at both doses. Concentrations of furosemide were...
Gokbulut C, Nolan AM, McKellar QA.The present study was carried out to investigate whether the pharmacokinetics of avermectins or a milbemycin could explain their known or predicted efficacy in the horse. The avermectins, ivermectin (IVM) and doramectin (DRM), and the milbemycin, moxidectin (MXD), were each administered orally to horses at 200 microg/kg bwt. Blood and faecal samples were collected at predetermined times over 80 days (197 days for MXD) and 30 days, respectively, and plasma pharmacokinetics and faecal excretion determined. Maximum plasma concentrations (Cmax) (IVM: 21.4 ng/ml; DRM: 21.3 ng/ml; MXD: 30.1 ng/ml) w...
Schatzman U, Armbruster S, Stucki F, Busato A, Kohler I.The analgesic potency of butorphanol 25 microg/kg bodyweight (BW) and levomethadone 100 microg/kg BW, administered together with detomidine 10 microg/kg BW, was measured in twelve Warmblood horses in a randomized, blinded cross-over study. Detomidine with saline 10 ml 0.9% was used as placebo. The nociceptive threshold was determined using a constant current and a pneumatic pressure model for somatic pair Detomidine alone and in combination with butorphanol or levomethadone caused a significant temporary increase (P < 0.05) of the nociceptive threshold with a maximum effect within 15 min and a...
Butt TD, Bailey JV, Dowling PM, Fretz PB.The purpose of this study was to compare the synovial fluid concentrations and pharmacokinetics of amikacin in the equine limb distal to the carpus following intraosseous and intravenous regional perfusion. The front limbs of 6 horses were randomly assigned to either intraosseous or intravenous perfusion. A tourniquet was placed distal to each carpus and the limb perfused with 500 mg of amikacin. Systemic blood samples and synovial fluid samples were collected over 70 min from the distal interphalangeal (DIP) joint, metacarpophalangeal joint, and digital flexor sheath. The tourniquet was remov...
Takeda A, Tanaka H, Shinohara T, Ohtake I.A sample preparation method for mass chromatographic detection of doping drugs from horse plasma is described. Bond Elut Certify (1 g/6 ml) is used for the extraction of 4 ml of horse plasma. Fractionation is performed with 6 ml of CHCl3-Me2CO (8:2) and 5 ml of 1% TEA-MeOH according to its property. Simple and effective clean-up based on non-aqueous partitioning is adopted to remove co-eluted contaminants in both acid and basic fractions. Two kinds of 1-(N,N-diisopropylamino)-n-alkanes are co-injected with the sample into the GC-MS system for the calculation of the retention index. Total recov...
Fernandes DJ, Xu KF, Stewart AG.1. Airway wall remodelling (AWR), the structural change induced by acute and chronic inflammation in the airways, may be one of the most significant and difficult to reverse components of progressive asthma. 2. The mechanisms underlying the development of AWR are not known. Studies of only the most superficial wall structures of large airways can be conducted in living humans because of the degree of invasiveness required to measure airway structural changes. These studies reveal that currently available agents do not fully prevent or reverse AWR. Thus, animal models of asthma pathology may be...
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...
Benamou AE, Marlin DJ, Lekeux P.Based on previous in vitro studies, we hypothesised that endothelin (ET) would induce vasoconstriction in the pulmonary circululation of the horse and that this action would be mediated via ET(A) receptors. Pulmonary and systemic haemodynamic responses to endothelin-1 (ET-1), a potent vasoactive endogenous peptide, were investigated in 6 conscious, nonsedated horses at rest. Bolus i.v. injections of exogenous ET-1 (0.1, 0.2 and 0.4 microg/kg bwt) caused significant increases in pulmonary (PAP) and carotid (CAP) artery pressures, with peak increases of 79% and 51% for mean PAP and CAP, respecti...
Goetz TE, Munsiff IJ, McKiernan BC.The pharmacokinetic disposition of theophylline was determined by high-performance liquid chromatographic analysis of plasma samples from six healthy, adult horses following the administration of intravenous aminophylline (dosed at 9.94 mg/kg as theophylline), immediate-release aminophylline tablets (dosed at 9.94 mg/kg as theophylline), and sustained-release theophylline tablets (dosed at 20 mg/kg). The elimination rate constant (lambda z), apparent volume of distribution (Vz), and clearance (Cl) determined by compartmental analysis of the intravenous data were 0.07 +/- 0.01 h-1, 0.80 +/- 0.0...
Martins FC, Keating SC, Clark-Price SC, Schaeffer DJ, Lascola KM, DiMaio Knych H.To determine the physiologic and behavioral effects and pharmacokinetic profile of hydromorphone administered intravenously (IV) to horses. Methods: Prospective, randomized, crossover study. Methods: A group of six adult healthy horses weighing 585.2 ± 58.7 kg. Methods: Each horse was administered IV hydromorphone (0.025 mg kg; treatment H0.025), hydromorphone (0.05 mg kg; treatment H0.05) or 0.9% saline in random order with a 7 day washout period. For each treatment, physiologic, hematologic, abdominal borborygmi scores and behavioral data were recorded over 5 hours and fecal output was tota...
Labadia A, Rivera L, Costa G, Garcia-Sacristan A.alpha and beta-adrenergic receptors in detrusor muscle and bladder base of horses were investigated by in vitro responses of smooth muscle strips to exogenous agonist and antagonist drugs. Noradrenaline, isoprenaline and salbutamol induced relaxation of detrusor muscle strips which was significantly inhibited by propranolol and butoxamine suggesting that the response is mediated by beta-2 adrenergic receptors. In the urinary bladder base noradrenaline, phenylephrine and B-HT 920 induced strong contractile effects. These contractile responses were inhibited by the alpha antagonist phenoxybenzam...
MacKay RJ.The aim of the current study was to quantify sweating responses to intradermal terbutaline in normal horses. Seven Thoroughbred horses were used. Terbutaline (10-fold dilutions from 1000-0.001 mg/l) and a saline control were injected intradermally (0.1 ml/site) and sweat collected for 30 min into absorbent pads taped over each injection site. Tests were performed monthly for 11 successive months and temperature, relative humidity and dewpoint were measured at the time of testing. There was no significant effect (P<or=0.05) of environmental variables or time of year on sweat responses at any...
Gerhards H, Eberhardt C.Different doses of heparin were given to equids SC to establish 0.05 to 0.20 U of heparin/ml of plasma. Plasma heparin values and antithrombin III activities were assayed, using chromogenic substrate methods. Activated partial thromboplastin and thrombin times were determined, using conventional coagulation assays. Tests were run every hour (or every 2 hours for antithrombin III) for 12 hours from 5 groups of 5 equids each after single injection of 40, 60, 80, 100, or 125 U of calcium heparin/kg of body weight and from 11 equids after injection of 150 U of calcium heparin/kg. The smaller dose ...
Pascoe PJ, Steffey EP, Black WD, Claxton JM, Jacobs JR, Woliner MJ.The effect of 3 plasma concentrations of alfentanil on the minimum alveolar concentration (MAC) of halothane in horses was evaluated. Five healthy geldings were anesthetized on 3 occasions, using halothane in oxygen administered through a mask. After induction of anesthesia, horses were instrumented for measurement of blood pressure, airway pressure, and end-tidal halothane concentrations. Blood samples, for measurement of pH and blood gas tensions, were taken from the facial artery. Positive pressure ventilation was begun, maintaining PaCO2 at 49.1 +/- 3.3 mm of Hg and airway pressure at 20 +...
McReynolds CB, Yang J, Guedes A, Morisseau C, Garcia R, Knych H, Tearney C, Hamamoto B, Hwang SH, Wagner K, Hammock BD.There are few novel therapeutic options available for companion animals, and medications rely heavily on repurposed drugs developed for other species. Considering the diversity of species and breeds in companion animal medicine, comprehensive PK exposures in the companion animal patient is often lacking. The purpose of this paper was to assess the pharmacokinetics after oral and intravenous dosing in domesticated animal species (dogs, cats, and horses) of a novel soluble epoxide hydrolase inhibitor, EC1728, being developed for the treatment of pain in animals. Results: Intravenous and oral adm...
Sharrow-Reabe KL, Townsend WM.To compare the corneal anesthetic effects and duration of action of 2 ophthalmic anesthetic agents in horses. Methods: Prospective, randomized masked crossover study. Methods: 8 clinically normal adult horses. Methods: Corneal sensitivity was determined by measuring each eye's corneal touch threshold (CTT) with a Cochet-Bonnet esthesiometer. Each eye's baseline CTT was recorded prior to anesthetic instillation at 0 minutes and every 10 minutes thereafter for 60 minutes. Each eye was randomly assigned to receive 2 of 4 treatments: 0.5% aqueous proparacaine ophthalmic solution (aqueous proparaca...
Diez Bernal S, Studer N, Thormann W, Spadavecchia C, Levionnois O.To evaluate the effect of a romifidine infusion on antinociception and sedation, and to investigate its relationship with plasma concentration. Methods: Prospective, experimental, nonrandomized trial. Methods: A total of 10 healthy adult warmblood horses. Methods: Romifidine (loading dose: 0.08 mg kg, infusion: 0.03 mg kg hour) was administered intravenously over 120 minutes. Romifidine plasma concentrations were determined by capillary electrophoresis. Sedation quality and nociceptive thresholds were evaluated at regular time points before, during and after romifidine administration. The noci...
Hubbell JA, Sams RA, Schmall LM, Robertson JT, Hinchcliff KW, Muir WW.Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. Objective: To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. Methods: Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, h...
Maldonado PA, Montoya TI, Acevedo JF, Keller PW, Word RA.Although the positive effects of vaginal estrogens and the selective estrogen receptor modulator, ospemifene (OS), on the vaginal epithelium are well recognized, less is known regarding the effects of these therapies on the lower urinary tract or vaginal muscularis. Clinical evidence suggests that vaginally administered estrogen may improve overactive bladder-related symptoms. The objective of this study was to compare the effects of OS, vaginal conjugated equine estrogens (CEE), or both on the vaginal wall and lower urinary tract in a rat model of menopause. Contractile force of the bladder n...
De Gasperi D, Dzierzak SL, Muir P, Vanderby R, Brounts SH.OBJECTIVE To assess the effects of sedation on results of acoustoelastography of the superficial digital flexor tendons (SDFTs) in clinically normal horses. ANIMALS 27 clinically normal horses. PROCEDURES For each horse, the pathology index (PI) for the SDFT of each thoracic limb was determined by use of acoustoelastography at 4 locations (5, 10, 15, and 20 cm distal to the accessory carpal bone). Horses were evaluated before and after they were sedated with a combination of detomidine hydrochloride (0.01 mg/kg, IV) and butorphanol tartrate (0.01 mg/kg, IV). A repeated-measures ANOVA was used ...
Jernigan AD, Wilson RC, Booth NH, Hatch RC, Akbari A.In steers, horses and dogs, the comparative pharmacokinetics of yohimbine were determined using model-independent analysis. The intravenous dose of yohimbine was 0.25 mg/kg of body weight in steers, 0.075 or 0.15 mg/kg in horses, and 0.4 mg/kg in dogs. The mean residence time (+/- SD) of yohimbine was 86.7 +/- 46.2 min in steers, 106.2 +/- 72.1 to 118.7 +/- 35.0 min in horses, and 163.6 +/- 49.7 min in dogs. The mean apparent volume of distribution of yohimbine at steady state was 4.9 +/- 1.4 L/kg for steers, 2.7 +/- 1.0 to 4.6 +/- 1.9 L/kg for horses, and 4.5 +/- 1.8 L/kg for dogs. The total ...
Brink P, DeGraves F, Ravis WR, Johansen D, Campbell JD, Duran SH.To determine intravascular and intrasynovial pharmacokinetics of the R and S enantiomers of ketoprofen after i.v. and i.m. administration to horses. Methods: 6 healthy adult mares. Methods: Horses were weighed and ketoprofen (2.2 mg/kg of body weight) was administered i.v. Blood and synovial fluid samples were obtained and analyzed for concentrations of the R and S enantiomers by means of a modified reverse-phase stereospecific high-pressure liquid chromatographic method. Three weeks later, the procedure was repeated, except that ketoprofen was given IM. Protein binding of ketoprofen enantiome...
Stick JA, Chou CC, Derksen FJ, Arden WA.Isolated jejunal segments were perfused at a constant blood flow rate to determine simultaneously the effects of xylazine on intestinal vascular resistance, motility, compliance, and oxygen consumption in 12 anesthetized ponies. Xylazine was infused into the artery perfusing the intestinal segment (group 1), or into the jugular vein as a single IV bolus (group 2), or 3 times as IV boluses repeated at 10-minute intervals (group 3). Dose-response curves in group 1 indicated a biphasic response to the drug with vasoconstriction, increased motility, and increased oxygen consumption at lower doses ...
Whittem T, Firth EC, Hodge H, Turner K.This study examined the pharmacokinetics of steady-state phenylbutazone and single bolus intravenous gentamicin when administered together in the horse. The trial design was completed as a cross-over with seven thoroughbred horses. In the first phase each horse received 2.2 mg/kg gentamicin intravenously. After a 2-week washout, each horse received 4.4 mg/kg phenylbutazone intravenously every 24 h for 5 days. On the fourth day each horse received gentamicin as before. Plasma was harvested for gentamicin concentration determination by fluorescence polarization immunoassay and for phenylbutazone...
Knych HK, Mama K, Oakleaf M, Harrison LM, McKemie DS, Kass PH.The goal of this study was to determine plasma, urine, and synovial fluid concentrations and describe the effects on biomarkers of cartilage toxicity following intra-articular dexmedetomidine administration to horses. Methods: 12 research horses. Methods: Horses received a single intra-articular administration of 1 μg/kg or 5 μg/kg dexmedetomidine or saline. Plasma, urine, and synovial fluid were collected prior to and up to 48 hours postadministration, and concentrations were determined. The effects on CS846 and C2C were determined in synovial fluid at 0, 12, and 24 hours postadministration...
Johnson AL, Becker SE.Four studies were conducted to evaluate the effects of several physiologic and pharmacologic agents on serum prolactin concentrations in the nonpregnant mare. An increase in prolactin measured in response to administration of thyrotropin-releasing hormone (TRH; 50 micrograms, iv) was found not to vary (P = .20) in mares in estrus compared with mares in diestrus (5 to 10 d post-ovulation). Administration in the dopamine receptor blocker, metoclopramide (25 or 100 mg, im), rapidly increased serum prolactin, and the response was dependent on dose administered (total prolactin measured for 420 min...
Whelchel DD, Tennent-Brown BS, Giguère S, Epstein KL.To compare the pharmacodynamics of once daily and twice daily administration of low molecular weight heparin (LMWH) administration in horses. Methods: Randomized cross over study. Methods: Adult mixed breed healthy mares (n = 6). Methods: LMWH (dalteparin) was administered (50 U/kg subcutaneously) either every 12 or 24 hours for 3 consecutive days. Anti-factor Xa activity was measured before and at select time points after LMWH administration. Packed cell volume (PCV), platelet count, partial thromboplastin time (PTT), and anti-thrombin (AT) activity were monitored throughout the study. Result...
Morris J, Hoang D.This article discusses a rare case of isolated xylazine overdose in a human, treated successfully with naloxone. Xylazine, typically used as a veterinary tranquilizer, acts as a potent α2 adrenergic agonist, leading to sedation, muscle relaxation, and potential respiratory depression. In this case, a female mistakenly injected herself with xylazine mistaking it for a different medication. The report discusses naloxone's role beyond opioid overdose, especially regarding substances causing central nervous system (CNS) depression via mechanisms similar to those of opioids. While naloxone is trad...
Shokrollahi S, Mohammadi R, Sarrafzadeh-Rezaei F, Jalilzadeh-Amin G, Hashemi-Asl SM.The aim of this study was to compare the sedative and cardiovascular effects of the combination of xylazine-acepromazine versus xylazine-pregabalin - in horses. Four healthy crossbred horses were included in the study and assigned to two treatments. In treatment I (T1), the animals received xylazine hydrochloride (1.00 mg kg) in combination with acepromazine maleate (0.05 mg kg) intravenously. In treatment II (T2), the animals received intragastric administration of pregabalin (4.00 mg kg) followed by xylazine hydrochloride (1.00 mg kg) intravenously after 60 min. Head height above ground (HHA...
Swanton WE, Johnson R, Zhao Q, Schroeder C.To evaluate sedation and IV xylazine requirements to achieve 45% of baseline head height above ground measurements following oral (PO) administration of 2 trazodone dosages. Methods: 8 healthy, adult mares of various weights and breeds belonging to a university teaching herd were utilized in a blinded, crossover study design. Horses were randomly assigned to 1 of 3 PO treatments: control (no trazodone), trazodone at 3 mg/kg (low dose [LD]), or trazodone at 6 mg/kg (high dose [HD]). Before treatment, cardiac auscultation, EquiSed sedation score, and head height above ground (HHAG; cm) measureme...
Júnior GS, de Souza JV, de Souza Ferreira W, Florentino VRD, Valente TC, Comassetto F, Oleskovicz N.This study aimed to evaluate the sedation degree, cardiopulmonary effects, and detomidine-sparing during dental occlusal adjustment in standing horses using a bolus and constant rate infusion (CRI) of detomidine alone or in combination with butorphanol or methadone. In this randomized, blinded clinical trial, 24 healthy adult horses were assigned to the detomidine (DT), detomidine-butorphanol (DB), or detomidine-methadone (DM) group. DT received an intravenous bolus of detomidine (20 μg/kg), followed by CRI at 20 μg/kg/h. DB received detomidine (10 μg/kg) and butorphanol (0.02 mg/kg) boluse...
McLean AK, Falt T, Abdelfattah EM, Middlebrooks B, Gretler S, Spier S, Turoff D, Navas Gonzalez FJ, Knych HK.Recent approval of transdermal flunixin meglumine (FM) (Banamine®) in cattle has opened the door for the drug's potential application in other species. Transdermal FM could provide a safe and effective form of pain relief in donkeys. In order to evaluate the pharmacokinetics and effects of FM on anti-inflammatory biomarkers in donkeys, a three-way crossover study design was employed. In total, 6 healthy donkeys were administered transdermal (TD) FM at a dosage of 3.3 mg/kg, and oral (PO) and intravenous (IV) doses of 1.1 mg/kg body weight. Blood samples were collected over 96 h to determine t...
Vergara-Hernandez FB, Nielsen BD, Kottwitz JJ, Panek CL, Robison CI, Paris BL, Welsh TH, Bradbery AN, Leatherwood JL, Colbath AC.To determine the single-dose pharmacokinetics of clodronate disodium (CLO) in juvenile sheep and the plasma protein binding (PPB) of CLO in juvenile sheep and horses. Methods: 11 juvenile crossbred sheep (252 ± 6 days) for the pharmacokinetic study. Three juvenile crossbred sheep (281 ± 4 days) and 3 juvenile Quarter Horses (599 ± 25 days) for PPB analysis. Methods: CLO concentrations were determined using liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental analysis from plasma samples obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, and 72 hours ...
CLARKE EG.This research article explores the topic of doping racehorses, looking at the history of the practice, the reasons for it, various methods used, and the substances utilized. It also presents […]
Hanna CJ, Eyre P.Trimetaquinol [TMQ: 1-(3’,4‘,5’-trimethoxybenzyl)6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride] a potential p-sympathomimetic bronchodilator (Iwasawa & Kiyomoto 1967), has been shown to be an effective tracheal smooth muscle relaxant in guineapigs (Iwasawa & Kiyomoto 1967; Brittain 1972; Brittain et a1 1970, 1976) and an inhibitor of experimental bronchospasm in guinea-pigs and cats (Brittain et a1 1970; Brittain 1972). In addition, clinical studies with TMQ indicated that the drug was an effective bronchodilator in mild to moderate asthma (Yamamura & Kishimoto 1968). It may...
Duvivier DH, Votion D, Vandenput S, Art T, Lekeux P.To determine the effects of the dry powder inhalation (DPI) of ipratropium bromide (ipratropium) on the airways of health horses and the dose-response curve in horses suffering from chronic obstructive pulmonary disease (COPD) by means of pulmonary function tests, five healthy horses were first studied. Ipratropium (2400 micrograms ipratropium horse-1) was contained in gelatine capsules and administered using a dry powder device connected to an adapted face mask. Pulmonary function tests were recorded before inhalation and 15 and 60 min after inhalation. No modification of pulmonary function w...
