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.
Marquardt J, Heymer J, Heinz H, Adolf GR, Deegen E.Recombinant equine interferon-beta 1 (reqIFN-beta 1) induces an antiviral state in blood mononuclear cells (BMC) of horses. Maximal protection against replication of vesicular stomatitis virus is achieved 6 hours after treatment with IFN in vitro and in vivo. Duration of the protective effect depends on the dose of IFN in vitro and in vivo. Availability of reqIFN-beta 1 in cultures of BMC for up to 48 hours does not prolong the antiviral state. The protective effect on BMC after treatment with IFN has similar duration in vivo and in vitro. Monitoring of the effect of IFN in vivo is, thus, simp...
LeBlanc M, Neuwirth L, Mauragis D, Klapstein E, Tran T.The effects of oxytocin on the percentage of technetium 99m albumin colloid (99mTc-microAA), cleared from the uterine lumen was measured in 13 mares. Scintigraphy was performed during 4 consecutive oestrous cycles, on Day 3 of oestrus during Cycles one and 3 and 48 h after ovulation during Cycles 2 and 4. Oxytocin (20 iu) was given i.v. after the initial scintigraphy image during Cycles 3 and 4. Seven multiparous mares (Group 1) were classified as 'susceptible' and 6 mares (2 nulliparous and 4 multiparous; Group 2) were classified as 'resistant' to endometritis. All mares cleared > 90% of 99mT...
Hare JE, Viel L, O'Byrne PM, Conlon PD.Some young horses with clinical signs of small airway disease demonstrate increased metachromatic cell numbers on bronchoalveolar lavage. The purpose of this study was to determine the effect of sodium cromoglycate treatment on clinical signs, bronchoalveolar lavage cytology and bronchoalveolar lavage histamine parameters in these horses. Twelve racehorses (age: 3.4 +/- 1.6 years) with a history of respiratory embarrassment at exercise, clinical signs of obstructive airway disease and bronchoalveolar lavage metachromatic cell differential greater than 2% were selected. Horses were randomly ass...
Lees P, McKellar Q, May SA, Ludwig B.The pharmacokinetics and pharmacodynamics of the nonsteroidal anti-inflammatory drug (NSAID) carprofen have been evaluated in 6 horses using a model of acute non-immune inflammation. Following intravenous administration of 0.7 mg racemic carprofen/kg bwt, mean values for pharmacokinetic parameters were 18.1 h (elimination half-life); 0.25 l/kg (volume of distribution, Vd[area]); 58.9 ml/min (clearance); and 57.9 micrograms/ml.h (area under plasma concentration time curve). Mean exudate:plasma concentration ratios exceeded 1.0 at all sampling times between 2 and 48 h. Swelling at the site of ac...
Hildebrand SV, Hill T.Evoked hind limb digital extensor tension (hoof twitch) was maintained at 40% of baseline for 1 h by atracurium infusion in 7 horses anaesthetised with halothane. After 1 h, atracurium was discontinued and hoof twitch allowed to recover to 75%. Atracurium was again given by infusion to maintain 40% twitch for a second hour, then 2 mg gentamycin/kg bwt were given i.v. Atracurium infusion was continued for a third hour, and then hoof twitch was again allowed to recover spontaneously to 75%. Gentamycin reduced twitch strength from 40 +/- 1% (mean +/- sem) to 29 +/- 4% within 7.0 +/- 1.5 min (P = ...
Obi T, Kabeyama A, Nishio A.In coronary arterial rings isolated from horse, norepinephrine (NE)(10(-7) - 10(-5) M) induced concentration-dependent contractions which were not influenced by endothelial denudation. Prazosin (alpha 1-antagonist) inhibited the contraction, but yohimbine (alpha 2-antagonist) did not, and propranolol (beta-antagonist) enhanced the contraction. Pretreatment with phentolamine (10(-5) M) (alpha-antagonist) converted the contraction induced by NE to relaxation in coronary rings precontracted with ONO11113 (thromboxane A2 derivative). The relaxation was not influenced by removal of the endothelium,...
Sarasola P, McKellar QA.Ampicillin is an antibiotic commonly administered to horses by both the intramuscular (i.m.) and the intravenous (i.v.) route. Its physicochemical properties restrict its absorption after oral administration and explain its rapid elimination from the body. To prolong the effects of ampicillin in the horse, attempts have been made to alter its elimination and absorption rates. The alteration of urinary pH did not change the plasma disposition of the antibiotic but when probenecid was administered concurrently with ampicillin, a significant reduction of total body clearance was achieved. Ampicil...
Tesarowski DB, Viel L, McDonell WN, Newhouse MT.The purpose of the study was to administer therapeutic aerosol generated by metered-dose inhalers to horses exhibiting clinical signs of heaves using a compact inhalation device developed for human medicine. It was fitted to a custom face mask in order to study the effect of an inhaled beta 2-agonist, fenoterol. Pulmonary function testing was performed on six horses following an acute exacerbation of heaves, characterized by tachypnea, wheezes, crackles, and spasmodic cough. Horses inhaled fenoterol in 1 mg increments administered as one 200 microgram puff every 5-10 s with the recording of da...
Pascoe PJ, Black WD, Steffey EP.We measured plasma concentrations of alfentanil in two horses after three different randomly ordered treatments. Each horse received halothane in oxygen by mask followed by a bolus dose of alfentanil 60 micrograms kg-1 i.v., halothane in oxygen by mask followed by an i.v. alfentanil infusion for 120 min and xylazine and ketamine followed by halothane and a bolus dose of alfentanil 60 micrograms kg-1 i.v. Halothane was maintained at 1.05-1.07% end-tidal concentration with a PaCO2 of 6-7.3 kPa. The plasma concentration-time curves were similar after bolus and infusion doses of alfentanil with ha...
Jaglan PS, Roof RD, Yein FS, Arnold TS, Brown SA, Gilbertson TJ.Ceftiofur sodium, a broad spectrum cephalosporin antibiotic approved for veterinary use, is metabolized to desfuroylceftiofur which is conjugated to micro as well as macromolecules. Twelve horses, weighting 442-618 kg, were injected intramuscularly with a single dose of 2.2 mg ceftiofur/kg (1.0 mg/lb) body weight. Blood was collected at various intervals over 24 h after treatment. Three groups of four horses each were euthanized and lungs were collected at 1, 12, and 24 h after treatment. The concentration of desfuroylceftiofur and desfuroylceftiofur conjugates in the plasma and lungs was dete...
Van Duijkeren E, Vulto AG, Van Miert AS.The indications for use, side-effects, and pharmacokinetic parameters of trimethoprim, sulfonamides and their combinations in the horse are reviewed. Trimethoprim/sulfonamide (TMPS) combinations are used for the treatment of various diseases caused by gram-positive and gram-negative bacteria, including infections of the respiratory tract, urogenital tract, alimentary tract, skin joints and wounds. TMPS combinations can be administered orally, since absorption from the gastrointestinal tract is relatively good. However, peak serum concentrations can vary significantly between individual horses....
Ewing PJ, Burrows G, MacAllister C, Clarke C.The pharmacokinetic properties of four erythromycin formulations were compared in six adult horses after administration of single and multiple oral doses. Formulations of erythromycin administered were estolate and phosphate given 37.5 mg/kg every 12 h and 25 mg/kg every 8 h, and stearate and ethylsuccinate given 25 mg/kg every 8 h. Areas under the curve (AUC) and maximum plasma erythromycin concentrations (Cmax) were equal or greater (P > or = 0.05) following administration of erythromycin phosphate and stearate compared with those values following administration of erythromycin estolate or e...
Aviad AD, Houpt JB.Various molecular weight hyaluronic acid (HA) preparations have been injected into joints for the treatment of human and equine osteoarthritis. A therapeutic advantage has been claimed for commercial products with a molecular weight in the range found in normal synovial fluid (SF), compared to lower molecular weight products. But a correlation between molecular weight and efficacy is not borne out by an analysis of the available literature on clinical results. SF viscosity, HA concentration, HA molecular weight and rate of synthesis in joint disease. It is proposed that the beneficial effect o...
Miyamoto A, Nishio A.The vasomotor effects of histamine on isolated bovine and equine basilar arteries were examined. Histamine induced contractions in both these preparations. The maximal response to and pEC50 value for histamine of the equine artery were larger than those of bovine tissue. Similar results were obtained with endothelium-denuded basilar arteries. Diphenhydramine (H1-receptor antagonist) inhibited histamine-induced contractions of the basilar arteries from both species in a concentration-dependent manner and its pA2 values (with 95% confidence limits) were 7.61 (7.39-7.83) and 8.15 (8.01-8.29) for ...
Dyke TM.Drugs of relevance to equine practice that modify the central nervous system (CNS) can be broadly classified as depressants or stimulants. The pharmacologic mechanisms of action, uses, and side effects of selected CNS depressant and stimulant drugs in horses are reviewed. Knowledge of the way these CNS-modifying drugs may affect performance is limited.
Light GS, Hellyer PW.We investigated the influence of parasympathetic tone on the arrhythmogenic dose of dobutamine in horses premedicated with xylazine, anesthetized with guaifenesin and thiamylal, and maintained on halothane in oxygen. Six horses were used in 12 randomized trials. In each trial, after end-tidal halothane concentration was stabilized at 1.1% (1.25 times minimum alveolar concentration [MAC]) in oxygen, either saline solution (0.02 ml/kg of body weight) or atropine (0.04 mg/kg) was administered IV. Five minutes later, dobutamine infusion was started at dosage of 2.5 micrograms/kg/min, IV. The dobut...
Wilcke JR, Crisman MV, Sams RA, Gerken DF.Single doses (2.2 mg/kg of body weight) of phenylbutazone (PBZ) were administered IV to 6 neonatal horses (5 to 17 hours old at time of dosing). Plasma concentrations of PBZ and its metabolite oxyphenbutazone were monitored serially for 120 hours after drug administration. Pharmacokinetic variables were calculated, using 1- and 2-compartment open models. Descriptive equations from the best model for each foal were then used to derive model-independent variables describing PBZ disposition. Median volume of distribution at steady-state was 0.274 L/kg (range, 0.190 to 0.401 L/kg). Median terminal...
Foster AP, Cunningham FM, Andrews MJ, Lees P.The effects of the selective platelet activating factor (PAF) receptor antagonist WEB 2170 on PAF-induced responses in equine cells and tissues have been examined and compared with those of WEB 2086. In initial experiments WEB 2170 was shown to inhibit in vitro platelet aggregation in a dose-dependent, competitive reversible manner (pA2 = 7.21). Co-administration of the antagonists with either PAF or histamine also inhibited PAF, but not histamine, induced wheal formation and PAF-induced neutrophil accumulation in vivo in equine skin. Intravenous (i.v.) administration of both drugs at a dose o...
Daunt DA, Dunlop CI, Chapman PL, Shafer SL, Ruskoaho H, Vakkuri O, Hodgson DS, Tyler LM, Maze M.Cardiopulmonary and behavioral responses to detomidine, a potent alpha 2-adrenergic agonist, were determined at 4 plasma concentrations in standing horses. After instrumentation and baseline measurements in 7 horses (mean +/- SD for age and body weight, 6 +/- 2 years, and 531 +/- 48.5 kg, respectively), detomidine was infused to maintain 4 plasma concentrations: 2.1 +/- 0.5 (infusion 1), 7.2 +/- 3.5 (infusion 2), 19.1 +/- 5.1. (infusion 3), and 42.9 +/- 10 (infusion 4) ng/ml, by use of a computer-controlled infusion system. Detomidine caused concentration-dependent sedation and somnolence. The...
Gerken DF, Sams RA.Although all the factors discussed in this article may have an effect on drug withholding time estimates, the factors that have the potential for the greatest effect or that have been found to cause positive tests in the past are 1. Dosage: Increasing the drug dosage will require a longer withholding time. 2. Dosing interval: Narrowing the dosing interval will require a longer withholding time. 3. Administration route: In general, oral administration results in lower peak plasma concentrations but may result in longer excretion in the urine and therefore longer withholding time. 4. Drug intera...
Baker SJ, Gerring EL.We investigated the effects of a range of IV administered doses of omeprazole (0.125 to 2.0 mg/kg of body weight) on gastric pH (monitored by indwelling electrode) and plasma gastrin concentration, compared with those of IV administered ranitidine (1.0 mg/kg) in 4 Welsh mountain-type ponies. Pharmacokinetic variables of IV administered omeprazole also were examined. Episodes of high gastric pH in the basal state obscured the effect of acid suppression on intragastric pH; however, omeprazole induced dose-dependent increase in mean gastric pH (P < 0.01) during the 11 hours after its administr...
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...
Puigdemont A, Ramis J, Guitart R, Arboix M.Usually, smaller mammals have higher clearances per unit body mass than do larger mammalian species. When clearance and other pharmacokinetic parameters are correlated with internal physiological processes, species tend to dispose of drugs at a similar pace. The first application of this concept is pharmacokinetic time, expressed with different units: Kallynochron, Apolysichron, Dienetichron, and Syndesichron. The present work describes pharmacokinetic time in these units from data obtained with propafenone in eight animal species: mouse, rat, rabbit, dog, sheep, human, cow, and horse. Additio...
Firth EC, Whittem T, Nouws JF.Six adult ponies were injected in the same intramuscular site with kanamycin sulphate (10 mg/kg). Two hours later, arthrocenteses of the right metacarpophalangeal, radio-carpal, intercarpal, tibio-tarsal and metatarsophalangeal joints were performed within 3 minutes. Arthrocenteses of the same joints on the left side were conducted 5 hours later. When expressed as a percentage of plasma drug concentration, differences in synovial fluid drug concentration between the joints sampled at 2 and 5 hours after injection were not detected.
Delbeke FT, Vynckier L, Debackere M.A high performance liquid chromatographic method is described to determine the anti-inflammatory drug suxibuzone (SXB) and its major metabolites phenylbutazone (PBZ) and oxyphenbutazone (OPBZ) in equine plasma and urine. When suxibuzone (6 mg/kg) was administered intravenously (i.v.) or orally (p.o.) no parent drug was detected in plasma or in urine. The disposition of the metabolite PBZ (i.v.) could be described by a 2 compartment model with a beta half-life varying from 7.40 to 8.35 h. Due to severe side effects the use of i.v. suxibuzone should not be encouraged in the horse. PBZ and OPBZ w...
Yu M, Robinson NE, Wang Z, Derksen FJ.The effects of epithelial removal and cyclooxygenase inhibition on contractions induced by exogenous acetylcholine (ACh) and electrical field stimulation (EFS) were evaluated in horse tracheal strips and bronchial rings. Epithelial removal potentiated the response to ACh but had no influence on the response to EFS. The effect of epithelial removal was not altered by pretreating the tissues with meclofenamate, a cyclooxygenase inhibitor. In trachealis strips, meclofenamate augmented contractions induced by EFS but not by ACh. In bronchial rings, meclofenamate augmented EFS-induced contraction t...
Hashem A, Keller H.The pharmacokinetics and pharmacological efficacy of orally (p.o.) administered acepromazine were studied and compared with the intravenous (i.v.) route of administration in a cross-over study using six horses. The oral kinetics of acepromazine can be described by a two-compartment open model with first-order absorption. The drug was rapidly absorbed after p.o. administration with a half-life of 0.84 h, tmax of 0.4 h and Cmax of 59 ng/ml. The elimination was slower after p.o. administration (half-life 6.04 h) than after i.v. injection (half-life 2.6 h). The bioavailability of the orally admini...
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 +...
Wood T, Weckman T, Woods WE, Tobin T, Dougherty J.Variable interval (VI) reinforcement scheduling is a specific type of operant conditioning that is sensitive to drug effects even when overt clinical signs of the drug have diminished. Six horses were conditioned to break a light beam with a head-bobbing movement and this behaviour was reinforced with a reward of clean oats (approximately 30 mg/reinforcement). Initial training procedures included familiarisation with the behavioural equipment and fixed-ratio reinforced scheduling. To establish baseline rates of behaviour, the horses were converted to a variable interval (60 secs) reinforcement...
Gustafsson K, Tatz AJ, Dahan R, Britzi M, Soback S, Sutton GA, Kelmer G. The aim of this study was to determine the time (T) to the maximum concentration (C) of amikacin sulphate in synovial fluid of the radiocarpal joint (RCJ) following cephalic intravenous regional limb perfusion (IVRLP) using 2 g of amikacin sulphate. Methods:  Cephalic IVRLP was performed with 2 g of amikacin sulphate diluted in 0.9% NaCl to a total volume of 100 mL in six healthy adult mixed breed mares. An Esmarch's rubber tourniquet was applied for 30 minutes and the antibiotic solution was infused through a 23-gauge butterfly catheter. Synovial fluid was collected from the RCJ ...
Easton S, Pinchbeck GL, Bartley DJ, Hotchkiss E, Hodgkinson JE, Matthews JB.The aim of this study was to determine practices, attitudes and experiences of UK prescribers of anthelmintics for horses and livestock. A questionnaire was sent by direct email to groups licenced to prescribe these medicines. These were veterinarians, Suitably Qualified Persons (SQPs, registered with the Animal Medicines Training Regulatory Authority) and veterinary pharmacists. The survey was also advertised through social media. It comprised questions relating to demographics, training experiences, current prescribing practices, as well as personal opinions on anthelmintic selection, diagno...
Raekallio M, Vainio O, Karjalainen J.Detomidine (10 micrograms/kg and 20 micrograms/kg) was administered to seven horses with and without epinephrine infusion (0.1 microgram/kg/min) from 5 minutes before to 5 minutes after detomidine injection. One or more single supraventricular premature heartbeats were observed in three horses after detomidine administration. Epinephrine infusion did not modify the incidence of cardiac arrhythmias in detomidine-treated horses at the doses tested. Relatively high momentary peak systolic pressures were registered in some horses after detomidine administration during epinephrine infusion. The hig...
Abo El Sooud K.The pharmacokinetics of gentamicin was studied in lambs, calves and foals, respectively after single intravenous (i.v.) injections of 5 mg kg(-1) body weight. The plasma concentration-time curves of gentamicin sulphate were best fitted to follow a two-compartment open model in calves and foals and a three-compartment open model in lambs. Gentamicin showed high plasma level at 5 min post-injection. Then its concentration decreased gradually until its minimum detectable level at 10 and 12 h post-injection in foals and calves, respectively, was reached. In contrast, the plasma concentrations were...
Hinchcliff KW, McKeever KH, Muir WW, Sams RA.The effect of premedication with phenylbutazone on systemic hemodynamic and diuretic effects of furosemide was examined in 6 healthy, conscious, mares. Mares were instrumented for measurement of systemic hemodynamics, including cardiac output and pulmonary arterial, systemic arterial, and intracardiac pressures, and urine flow. Each of 3 treatments was administered in a randomized, blinded study; furosemide (1 mg/kg of body weight, IV) only, phenylbutazone (8.8 mg/kg, PO, at 24 hours and 4.4 mg/kg, IV, 30 minutes before furosemide) and furosemide, or 0.9% NaCl. Phenylbutazone administration si...
Rubie S, Robinson NE, Stoll M, Broadstone RV, Derksen FJ.Six horses that developed acute airway obstruction (heaves) when housed in a barn and fed poor-quality hay were studied. Airway obstruction was verified by a maximal change in pleural pressure during tidal breathing (delta Pplmax) of at least 15 cmH2O. Frusemide (1.0 mg/kg bwt) or an equivalent volume of vehicle was then administered intravenously (iv) and lung function was measured 15, 30, 60, 120, 180, 240 and 300 mins after drug administration. The effect of frusemide on lung function was also studied after treatment of horses with the cyclooxygenase inhibitor flunixin meglumine (1.1 mg/kg ...
Spensley MS, Baggot JD, Wilson WD, Hietala SK, Mihalyi JE.Plasma and endometrial tissue concentrations of ticarcillin were measured in healthy mares. In the first of the 3 separate phases comprising the study, ticarcillin disodium (30 mg/kg) was administered IV. The mean peak concentration in endometrial tissue, 12.9 micrograms/g, was attained at 30 minutes. The plasma half-life of the drug in the 6 mares was 0.83 +/- 0.22 hour. Six grams of the drug was diluted in 250 ml of sodium chloride injection USP (2nd phase) and in 60 ml of sodium chloride injection USP (3rd phase). These dilutions were administered by intrauterine infusion. In phase 2, the m...
Kuroda T, Nagata SI, Tamura N, Mita H, Kusano K, Mizobe F, Takizawa Y, Fukuda K, Kasashima Y.To investigate the pharmacokinetics and antihistaminic effects (pharmacodynamics) of olopatadine in a small population of healthy horses after administration via nasogastric tube. Methods: 4 healthy adult Thoroughbreds. Methods: Olopatadine (0.1 mg/kg, once) was administered via nasogastric tube. Blood samples were collected at predetermined time points for pharmacokinetic analyses of the drug in plasma. Olopatadine effects were investigated by measurement of cutaneous wheals induced by ID histamine injection (0.1 mL [10 μg]/injection) at predetermined time points. Inhibition effect ratios we...
Frias AF, Mársico F, Gómez de Segura IA, Nascimento PR, Nascimento A, Soares JH, Almosny NR.To characterize responses to different doses of propofol in horses pre-medicated with xylazine. Methods: Six adult horses (five females and one male). Methods: Each horse was anaesthetized four times with either ketamine or propofol in random order at 1-week intervals. Horses were pre-medicated with xylazine (1.1 mg kg-1 IV over a minute), and 5 minutes later anaesthesia was induced with either ketamine (2.2 mg kg-1 IV) or propofol (1, 2 and 4 mg kg-1 IV; low, medium and high doses, respectively). Data were collected continuously (electrocardiogram) or after xylazine administration and at 5, 1...
Dyke TM, Hinchcliff KW, Sams RA.The objectives of this study were to determine the effect of phenylbutazone premedication on the pharmacokinetics and urinary excretion of frusemide in horses; and on frusemide-induced changes in urinary electrolyte excretion. Six Standardbred mares were used in a 3-way crossover design. The pharmacokinetics and renal effects of frusemide (1 mg/kg bwt i.v.) were studied with and without phenylbutazone premedication (8.8 mg/kg bwt per os 24 h before, followed by 4.4 mg/kg bwt i.v. 30 min before frusemide administration). A control (saline) treatment was also studied. Administration of frusemide...
Stevenson AJ, Weber MP, Todi F, Young L, Beaumier P, Kacew S.Plasma and urinary concentrations of procaine were examined in Standardbred mares after subcutaneous administration of various doses (80 mg to 1600 mg) of procaine hydrochloride. Regardless of dose, peak plasma procaine values occurred within 1 h, but remained detectable in a dose-dependent manner, with procaine present at 1 h with the 80 mg dose and 6 h at the 1600 mg dose. Similarly, peak urinary procaine concentrations were attained within 1.5 to 3 h, irrespective of dose, while detection time was dose-dependent, being 23 h for 80-200 mg doses but as long as 30-54 h with the 1600 mg dose. W...
Knych HK, McKemie DS, Kass PH, Stanley SD, Blea J.Ketoprofen is an anti-inflammatory drug that is commonly administered to racehorses for the alleviation of musculoskeletal pain and inflammation. This study represents a comprehensive examination of the metabolism (in vivo and in vitro), pharmacokinetics and ex vivo pharmacodynamics, of ketoprofen in horses. The in vitro metabolism as well as specific enzymes responsible for metabolism was determined by incubating liver microsomes and recombinant CYP450 and UGT enzymes with ketoprofen. For the in vivo portion, 15 horses were administered a single intravenous dose of 2.2-mg/kg ketoprofen. Blood...
Delbeke FT, Debackere M, Vynckier L.A high-performance liquid chromatographic method to measure urinary indomethacin levels is described. In 0.5 ml urine, 1 micrograms/ml of indomethacin could be detected. Alkaline hydrolysis of urine resulted in the decomposition of indomethacin. When two suppositories of Indocid corresponding to 200 mg indomethacin were administered rectally to four horses the drug was rapidly absorbed and remained detectable in urine from 1 to 12 h. The excretion rate peaked after 2-3 h while the maximal concentration ranged from 18.5 to 80.6 micrograms/ml. Only 8 to 16% of the indomethacin dose was eliminate...
el-Komy AA.The pharmacokinetics of piperacillin (430 mg/kg.b.wt.) and cephapirin (20 mg/kg.b.wt.) were investigated following a single intravenous and intramuscular injection in normal mares. The serum concentration-time curve following a single intravenous injection of both antibiotics obeyed a two-compartment open model. After intravenous dose, piperacillin and cephapirin were transferred from central to peripheral compartment (k12) with values 0.46 and 0.52 h-1, while their passages from peripheral to central compartment (k21) were equal to 0.56 and 0.49 h-1, respectively. The elimination half-lives [...
Adler DMT, Jørgensen E, Cornett C.To determine the synovial fluid (SF) concentrations of lidocaine and mepivacaine after intra-articular injection with clinically relevant doses to the distal interphalangeal (DIP), metacarpophalangeal (MCP), middle carpal (MC), and tarsocrural (TC) joint at two different time points after injection in order to be able to compare concentrations with previously established concentrations associated with cytotoxicity and antimicrobial activity. Unassigned: In the first of two experiments, 20 joints (5 MC, 5 MCP, 10 DIP joints) of five horses under general anesthesia were injected with clinically ...
Gordon E, Sandquist C, Cebra CK, Heidel J, Poulsen K, Schlipf JW.To evaluate whether topical ocular application of 1% morphine sulfate would change corneal sensitivity and to identify the duration of action. Methods: Eight healthy adult horses. Methods: Corneal touch threshold (CTT) was measured in the center of one randomly selected eye of each horse by Cochet-Bonnet esthesiometer (Luneau Cochet-Bonnet Esthesiometer; Western Ophthalmics, Lynnwood, WA, USA). Immediately following baseline CTT measurement, 0.3Â ml of 1.0% preservative-free morphine sulfate (Morphine Sulfate 25Â mg/ml Preservative-free; Hospira, Lake Forest, IL, USA) (3Â mg) was applied to th...
Luethy D, Robinson MA, Stefanovski D, Haughan J, Torcivia C, Kowalski A, Ford M, You Y, Missanelli J, Slack J.Cardiac drugs with defined pharmacological parameters in horses are limited. The objective of this study was to characterize the pharmacokinetic properties and cardiovascular effects of intravenous and oral metoprolol tartrate (MET) in horses. In a 2-period randomized cross-over design, MET was administered IV (0.04Â mg/kg) and PO (6Â mg/kg) once to six healthy adult horses. Horses were monitored via continuous telemetry and non-invasive blood pressure (NIBP). Blood samples were serially collected for 72Â h post-administration, and concentrations were determined by LC-MS/MS. Pharmacokinetics w...
Kilcoyne I, Nieto JE, Galuppo LD, Dechant JE.To determine the median time to maximum concentration (t) of amikacin in the synovial fluid of the tarsocrural joint following IV regional limb perfusion (IVRLP) of the drug in a saphenous vein of horses. Methods: 7 healthy adult horses. Methods: With each horse sedated and restrained in a standing position, a 10-cm-wide Esmarch tourniquet was applied to a randomly selected hind limb 10 cm proximal to the point of the tarsus. Amikacin sulfate (2 g diluted with saline [0.9% NaCl] solution to a volume of 60 mL) was instilled in the saphenous vein over 3 minutes with a peristaltic pump. Tarsocrur...
Fernández-Varón E, Ayala I, MarÃn 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...
Clarke CR, MacAllister CG, Burrows GE, Ewing P, Spillers DK, Burrows SL.Pharmacokinetics, CSF penetration, and hematologic effects of oral administration of pyrimethamine were studied after multiple dosing. Pyrimethamine (1 mg/kg of body weight) was administered orally once a day for 10 days to 5 adult horses, and blood samples were collected frequently after the first, fifth, and tenth doses. The CSF samples were obtained by cisternal puncture 4 to 6 hours after administration of the first, third, seventh, and tenth doses. Pyrimethamine concentration in plasma and CSF was quantified by gas chromatography, and plasma concentration-time data were analyzed, using a ...
Cuervo-Arango J, Newcombe JR.The objective of this study was to establish and characterize the relationship between the dose of cloprostenol (37.5, 250, 500 and 750 μg) and the age of the early corpus luteum (CL) (80, 88, 96, 104 and 112 h) on the luteolytic response of mares. Behavioural oestrus and ultrasonographic signs of return to oestrus were considered as the occurrence of full luteolysis. A total of 298 mares were divided into groups according to dose of cloprostenol and CL age. There was an effect of dose of cloprostenol (p < 0.001) and age of the CL at the time of treatment (p 0.05); and that of 500 similar...
Jurek KA, Schoonover MJ, Williams MR, Rudra P.To determine the influence of perfusate volume on synovial fluid amikacin concentrations in the joints of the hind limb after standing saphenous intravenous regional limb perfusion (IVRLP). Methods: Randomized crossover design. Methods: Six adult horses. Methods: Saphenous IVRLP was performed in 6 standing horses with 1 g of amikacin diluted with 0.9% NaCl to volumes of 10 ml, 60 ml, and 120 ml. Samples of synovial fluid from the tarsocrural, metatarsophalangeal, and hind limb distal interphalangeal joints were collected at 15 and 30 min after perfusate administration. Concentrations ...
Friebe M, Schumacher S, Stahl J, Kietzmann M.This study investigated synovial concentrations of acetylsalicylic acid (ASA) and its metabolite salicylic acid (SA) in the equine fetlock joint following systemic administration of ASA. Salicylates were chosen because SA is the only nonsteroidal anti-inflammatory drug for which threshold levels exist for plasma and urine in equine sports. To avoid animal experiments, the study was conducted using an ex vivo model of the isolated perfused equine distal limb in combination with plasma concentrations obtained from literature.Salicylate concentrations in the joint were determined using microdialy...
Greenblatt DJ, Engelking LR.Adult female ponies (130-225 kg) with chronically implanted external biliary fistulas (T-tubes) participated in three-way cross-over studies using either i.v. lorazepam (10 mg) or acetaminophen (2 g), two model drugs biotransformed mainly by hepatic conjugative reactions. The objectives were to determine the systemic pharmacokinetics, urinary and biliary excretion and degree of enterohepatic circulation (EHC) of these compounds. Trial conditions were: A: EHC intact, with blood and urine, but not bile, collected after i.v. drug administration; B: EHC interrupted, with blood, urine and bile coll...
Ishii H, Shibuya M, Leung GN, Yamashita S, Nagata SI, Kushiro A, Sakai S, Toju K, Okada J, Kawasaki K, Kusano K, Kijima-Suda I.For the purpose of doping control, this is the first report of accurate quantification of four critical structural isomers of nicotine metabolites (trans-3'-hydroxycotinine, cis-3'-hydroxycotinine, 5'-hydroxycotinine, and N'-hydroxymethylnorcotinine) in equine plasma and urine for the establishment of their elimination profiles. Besides, the pharmacokinetic studies of trans-3'-hydroxycotinine and N'-hydroxymethylnorcotinine in equine plasma and urine are also presented for the first time. Methods: The accurate quantification methods of the aforementioned four structural isomers in horse plasma...
Bidwell LA, Wilson DV, Caron JP.To measure concentrations of lidocaine serum after application of two 5% patches on horses. Methods: Prospective experimental trial Methods: Six client-owned, systemically healthy horses. Methods: The hair was clipped on the medial aspect above the carpus of both fore limbs and 2 patches of 5% lidocaine were applied within 30 minutes of jugular catheter placement and the area was then bandaged. Venous blood was drawn from a jugular vein catheter that was inserted using lidocaine as a local block. Samples were drawn immediately before and at 2, 4, 6, 8, and 12 hours after patch application. The...
Alexander SL, Irvine CH, Evans MJ.We used our nonsurgical technique for collecting pituitary venous blood to relate the dynamics of thyrotrophin-releasing hormone (TRH) secretion to the secretion patterns of both prolactin and thyrotrophin in periovulatory mares, either euthyroid (n = 5) or made hypothyroid by treatment with propyl-thiouracil (n = 5). Pituitary venous blood was collected continuously and divided into 1-min aliquots for 4 h. To test the effect of dopamine on the relationship between secretion patterns, sulpiride, a selective D2 receptor antagonist, was given i.m. after 2 h of sampling. Thorough testing of the m...
Hunyadi L, Datta P, Rewers-Felkins K, Sundman E, Hale T, Fajt V, Wagner S.The objective of this study was to determine the pharmacokinetic parameters of oclacitinib maleate as a top dress given to adult horses. Six adult horses with a mean weight of 528Â kg were administered a single dose of 0.5Â mg/kg oclacitinib maleate. Blood was collected prior to drug administration and at 15Â min, 30Â min, 45Â min, 1, 2, 4, 6, 8, 12, 24, 48, and 72Â h after treatment. Oclacitinib maleate plasma concentrations were measured by liquid chromatography/mass spectrometry. Pharmacokinetic parameters were found best to fit a one-compartment model. Mean C was 486Â ng/ml (range 423-549Â...
MacAllister CG, Sangiah S, Mauromoustakos A.Using video gastroscopy, the efficacy of a Histamine-H2 type receptor antagonist (WY 45, 727) was investigated in young ponies with spontaneous and experimentally induced gastric ulcers. Oral administration of WY 45, 727 at 2 mg/kg and 10 mg/kg of body weight every 12 hours for 14 days resulted in complete healing of spontaneous gastric ulcers in the non-glandular portion of the stomach in 2/5 (40%) and 3/4 (75%) of the ponies, respectively, compared (P < 0.05) to 0/5 (0%) placebo-treated ponies. After intramuscular administration of flunixin meglumine at 1.5 mg/kg body weight every 8 hours fo...
