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.
DiMaio Knych HK, Covarrubias V, Steffey EP.To describe selected pharmacodynamic effects of detomidine and yohimbine when administered alone and in sequence. Methods: Randomized crossover design. Methods: Nine healthy adult horses aged 9 ± 4 years and weighing 561 ± 56 kg. Methods: Three dose regimens were employed in the current study. 1) 0.03 mg kg(-1) detomidine IV, 2) 0.2 mg kg(-1) yohimbine IV and 3) 0.03 mg kg(-1) detomidine IV followed 15 minutes later by 0.2 mg kg(-1) yohimbine IV. Each horse received all three treatments with a minimum of 1 week between treatments. Blood samples were obtained and plasma analyzed for detomidin...
McGorum BC, Nicholas DR, Foster AP, Shaw DJ, Pirie RS.Bronchodilators are frequently used to attenuate airway obstruction in equine heaves (or recurrent airway obstruction). This study evaluated the selective (M(3) and M(1)) muscarinic antagonist revatropate, which offers potential advantages over non-specific antimuscarinic agents such as ipratropium. Protocol 1 assessed the response to inhaled revatropate (1, 2 and 7 mg) using a blinded, negative (inhaled saline) and positive (inhaled ipratropium bromide; 0.3, 0.7 and 2mg) controlled, dose escalation study, with six heaves horses. The lowest doses of revatropate and ipratropium induced a rapid ...
Ringer SK, Schwarzwald CC, Portier KG, Ritter A, Bettschart-Wolfensberger R.The objective of this study was to compare the cardiopulmonary effects of a xylazine or romifidine loading-dose, followed by a constant rate infusion (CRI) of the same α(2)-agonist. Nine research horses were treated in a randomized, blinded, crossover design with xylazine or romifidine. After instrumentation, a loading dose of intravenous xylazine (1mg/kg) or romifidine (80μg/kg) was administered, immediately followed by a CRI of xylazine (0.69mg/kg/h) or romifidine (30μg/kg/h) for a duration of 2h. Cardiopulmonary variables were recorded before bolus administration, during CRI, and for 1h ...
Stern JA, Doreste YR, Barnett S, Lahmers SM, Baumwart RD, Seino KK, Bonagura JD.Sustained narrow-QRS tachycardia of three months duration and left ventricular systolic dysfunction were identified in a fifteen-year-old Quarter Horse. No underlying cause for the tachyarrhythmia was found and no predisposing structural cardiac lesions were evident by echocardiography. Intravenous diltiazem and lidocaine were administered without achieving successful conversion of the arrhythmia. Oral quinidine therapy converted the tachyarrhythmia to sinus rhythm. Ventricular systolic dysfunction and chamber dilatation subsequently resolved. As with other species, echocardiographic features ...
Shrestha HK, Beg MA, Burnette RR, Ginther OJ.Horses are about five times more sensitive to the luteolytic effect of prostaglandin F2alpha (PGF) than cattle, as indicated by a recommended clinical dose of 5 mg in horses and 25 mg in cattle. Novel evaluations of the PGF plasma disappearance curves were made in mares and in heifers, and the two species were compared. Mares and heifers (n = 5) of similar body weight were injected (Min 0) intravenously with PGF (5 mg per animal). Blood was sampled every 10 sec until Min 3, every 30 sec until Min 5, every 10 min until Min 60, and every 30 min until Min 240. The mean PGF concentration was great...
de Vries A, Taylor PM, Troughton G, Liu B, Fowden AL, Sear JW.This study examined the pharmacokinetics of propofol by infusion in ponies using an analyser for the rapid measurement of propofol concentrations. The analyser (Pelorus 1000; Sphere Medical Ltd., Cambridge, UK) has a measurement cycle of approximately five minutes. Ten Welsh-cross ponies (weighing 135-300 kg) undergoing minor procedures were studied after premedication with acepromazine 0.03 mg/kg and detomidine 0.015 mg/kg. Anaesthesia was induced with ketamine 2 mg/kg and diazepam 0.03 mg/kg, and maintained with an infusion of propofol at an initial rate of 0.16 mg/kg/min for the first thirt...
Brainard BM, Epstein KL, LoBato DN, Kwon S, Darien BJ, Hurley DJ, Moore JN.Inflammation-induced P-selectin (CD62P) expression on platelets and endothelial cells facilitates interactions among platelets and polymorphonuclear leukocytes (PMN), and can also promote coagulation. The effects of clopidogrel and aspirin (ASA) on equine platelet CD62P expression were investigated. Six horses were treated in a cross-over design with clopidogrel (2mg/kg PO q 24) or ASA (5mg/kg PO q 24h) for 5 days. Platelets collected at 24, 72, 96, 120, and 168 h after the initiation of therapy were stimulated using 0.1 μg/mL thrombin, followed by flow cytometric analysis using anti-CD41/61 ...
Goodwin W, Keates H, Pasloske K, Pearson M, Sauer B, Ranasinghe MG.To determine the pharmacokinetics and pharmacodynamics of the neurosteroid anaesthetic, alfaxalone, in neonatal foals after a single intravenous (IV) injection of alfaxalone following premedication with butorphanol tartrate. Methods: Prospective experimental study. Methods: Five clinically healthy Australian Stock Horse foals of mean ± SD age of 12 ± 3 days and weighing 67.3 ± 12.4 kg. Methods: Foals were premedicated with butorphanol (0.05 mg kg(-1) IV) and anaesthesia was induced 10 minutes later by IV injection with alfaxalone 3 mg kg(-1) . Cardiorespiratory variables (pulse rate, respir...
Giguère S, Lee EA, Guldbech KM, Berghaus LJ.There are no studies investigating interactions between clarithromycin or azithromycin and rifampin or other commonly used antimicrobial agents against virulent isolates of Rhodococcus equi. In addition, there is no published data on the postantibiotic effects (PAEs) and pharmacodynamics properties of antimicrobial agents against R. equi. The objectives were to assess in vitro interactions, pharmacodynamics, and PAEs of 11 antimicrobial agents belonging to various antimicrobial classes against R. equi. Antimicrobial agents investigated (erythromycin, clarithromycin, azithromycin, rifampin, ami...
Soma LR, Uboh CE, Liu Y, Li X, Robinson MA, Boston RC, Colahan PT.This study investigated and compared the pharmacokinetics of intra-articular (IA) administration of dexamethasone sodium phosphate (DSP) into three equine joints, femoropatellar (IAS), radiocarpal (IAC), and metacarpophalangeal (IAF), and the intramuscular (IM), oral (PO) and intravenous (IV) administrations. No significant differences in the pharmacokinetic estimates between the three joints were observed with the exception of maximum concentration (Cmax ) and time to maximum concentration (Tmax ). Median (range) Cmax for the IAC, IAF, and IAS were 16.9 (14.6-35.4), 23.4 (13.5-73.0), and 46.9...
Steckler D, Naidoo V, Gerber D, Kähn W.To determine the intercyclic effect of oxytocin and carbetocin on equine myometrial tissue, the effect of the drugs was evaluated through pharmacokinetic and pharmacodynamic studies. The complete pharmacokinetic profile for oxytocin was unknown and had to be established. To do so, 25 IU of oxytocin were administered intravenously to six cycling mares and blood samples were collected before and 2, 4, 8, and 15 min after administration. The half-life of oxytocin was determined to be 5.89 min, the clearance rate 11.67 L/min, mean residence time (MRT) 7.78 min. The effective plasma concentration w...
Hewson J, Johnson R, Arroyo LG, Diaz-Mendez A, Ruiz-López JA, Gu Y, del Castillo JR.Healthy neonatal foals were treated with cefotaxime by bolus (40 mg/kg i.v. q6h for 12 doses; n=10) or by infusion (loading dose of 40 mg/kg i.v. followed by continuous infusion of a total daily dose of 160 mg/kg per 24 h for 3 days; n=5). Population pharmacokinetics was determined, and concentrations in cavity fluids were measured at steady state (72 h). Highest measured serum drug concentration in the bolus group was 88.09 μg/mL and minimum drug concentration (C(min)) was 0.78 μg/mL at 6-h postadministration (immediately before each next dose), whereas infusion resulted in a steady-state c...
Knych HK, Steffey EP, Stanley SD.To describe the pharmacokinetics of detomidine and yohimbine when administered in combination. Methods: Randomized crossover design. Methods: Nine healthy adult horses aged 9 ± 4 years and weighing of 561 ± 56 kg. Methods: Three dose regimens were employed in the current study. 1) 0.03 mg kg(-1) detomidine IV (D), 2) 0.2 mg kg(-1) yohimbine IV (Y) and 3) 0.03 mg kg(-1) detomidine IV followed 15 minutes later by 0.2 mg kg(-1) yohimbine IV (DY). Each horse received all three dose regimens with a minimum of 1 week in between subsequent regimens. Blood samples were obtained and plasma analyzed f...
Knych HK, Casbeer HC, McKemie DS, Arthur RM.Butorphanol is a narcotic analgesic commonly used in horses. Currently, any detectable concentration of butorphanol in biological samples collected from performance horses is considered a violation. The primary goal of the study reported here was to update the pharmacokinetics of butorphanol following intravenous administration, utilizing a highly sensitive liquid chromatography-mass spectrometry (LC-MS) assay that is currently employed in many drug-testing laboratories. An additional objective was to characterize behavioral and cardiac effects following administration of butorphanol. Ten exer...
Linardi RL, Stokes AM, Keowen ML, Barker SA, Hosgood GL, Short CR.To characterize the bioavailability and pharmacokinetics of oral and injectable formulations of methadone after IV, oral, and intragastric administration in horses. Methods: 6 healthy adult horses. Methods: Horses received single doses (each 0.15 mg/kg) of an oral formulation of methadone hydrochloride orally or intragastrically or an injectable formulation of the drug orally, intragastrically, or IV (5 experimental treatments/horse; 2-week washout period between each experimental treatment). A blood sample was collected from each horse before and at predetermined time points over a 360-minute...
Wojtasiak-Wypart M, Soma LR, Rudy JA, Uboh CE, Boston RC, Driessen B.Romifidine HCl (romifidine) is an α(2)-agonist commonly used in horses. This study was undertaken to investigate the pharmacokinetics (PK) of romifidine following intravenous (i.v.) administration and describe the relationship between PK parameters and simultaneously recorded pharmacodynamic (PD) parameters. Romifidine (80 μg/kg) was administered by i.v. infusion over 2 min to six adult Thoroughbred horses, and plasma samples were collected and analyzed using liquid chromatography-mass spectrometry. Limit of quantification was <0.1 ng/mL. PD parameters and arterial blood gases were measur...
Ringer SK, Portier KG, Fourel I, Bettschart-Wolfensberger R.To elaborate constant rate infusion (CRI) protocols for xylazine (X) and xylazine/butorphanol (XB) which will result in constant sedation and steady xylazine plasma concentrations. Methods: Blinded randomized experimental study. Methods: Ten adult research horses. Methods: Part I: After normal height of head above ground (HHAG = 100%) was determined, a loading dose of xylazine (1 mg kg(-1) ) with butorphanol (XB: 18 μg kg(-1) ) or saline (X: equal volume) was given slowly intravenously (IV). Immediately afterwards, a CRI of butorphanol (XB: 25 μg kg(-1) hour(-1)) or saline (X) was administer...
Grimsrud KN, Mama KR, Steffey EP, Stanley SD.To describe the pharmacodynamics and pharmacokinetics following an intravenous (IV) bolus dose of medetomidine in the horse. Methods: Prospective experimental trial. Methods: Eight, mature healthy horses age 11.7 ± 4.6 (mean ± SD) years, weighing 557 ± 54 kg. Methods: Medetomidine (10 μg kg(-1) ) was administered IV. Blood was sampled at fixed time points from before drug administration to 48 hours post administration. Behavioral, physiological and biochemical data were obtained at predetermined time points from 0 minutes to 24 hours post administration. An algometer was also used to measu...
Aljuffali IA, Brainard BM, Moore JN, Kwon S, Allen D, Robertson TP, Arnold RD.The purpose of this study was to determine the pharmacokinetics (PK) of the 5-HT(2A) receptor antagonist ketanserin in healthy adult horses, and to develop a computational model that could be used to optimize dosing. Plasma concentrations of ketanserin were determined using liquid chromatography with mass spectrometry after single and multiple intravenous administration in the horse. A two-compartment linear pharmacokinetic model described the plasma concentration-time profile of ketanserin after single and multiple doses in healthy horses; the terminal half-life was 11.5 h; steady-state volum...
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...
Müller JM, Wissemann J, Meli ML, Dasen G, Lutz H, Heinzerling L, Feige K.Whole blood pharmacokinetics of intratumourally injected naked plasmid DNA coding for equine Interleukin 12 (IL-12) was assessed as a means of in vivo gene transfer in the treatment of melanoma in grey horses. The expression of induced interferon gamma (IFN-g) was evaluated in order to determine the pharmacodynamic properties of in vivo gene transduction. Seven grey horses bearing melanoma were injected intratumourally with 250 µg naked plasmid DNA coding for IL-12. Peripheral blood and biopsies from the injection site were taken at 13 time points until day 14 post injection (p.i.). Samples w...
Dimaio Knych HK, Stanley SD.To characterize pharmacokinetics and pharmacodynamics of detomidine gel administered sublingually in accordance with label instructions to establish appropriate withdrawal guidelines for horses before competition. Methods: 12 adult racehorses. Methods: Horses received a single sublingual administration of 0.04 mg of detomidine/kg. Blood samples were collected before and up to 72 hours after drug administration. Urine samples were collected for 5 days after detomidine administration. Plasma and urine samples were analyzed via liquid chromatography-mass spectrometry, and resulting data were anal...
Lippert-Gruner M, Svestkova O.The acute management of spasticity following ABI is challenging. Contractures can occur during the acute phases of illness. The joints most affected are the shoulders and the ankles. Methods: A case study of a 48-year-old female patient who received local chemoneurolytic anti-spasticity therapy following a severe subarachnoid haemorrhage for pes equines deformity is presented to illustrate the role of focal neurotoxin therapy. Methods: The increasing spasticity in her legs was observed and could not be effectively treated with oral anti-spasticity agents or intensive physiotherapy. As spastici...
Baker WT, Frederick J, Giguere S, Lynch TM, Lehmkuhl HD, Slone DE.To evaluate the outcome in horses treated with a rolling technique or surgically for nephrosplenic entrapment of the large colon (NSE) and to examine the benefit of phenylephrine (PE) HCl on the efficacy of nonsurgical (rolling) management of NSE. Methods: Case series. Methods: Horses (n = 211) diagnosed with NSE by rectal palpation with or without ultrasonography, or at the time of exploratory celiotomy or necropsy. Methods: Medical records (January 1, 2001-September 1, 2008) were collected from horses diagnosed with NSE at 2 referral centers. Records were used to obtain signalment, physical ...
Beccar-Varela AM, Epstein KL, White CL.To determine the effects of experimentally induced synovitis of the radiocarpal joint on the intra-articular pharmacokinetics and pharmacodynamics of amikacin after intravenous regional limb perfusion (IVRLP). Methods: Randomized crossover experimental design. Methods: Adult horses (n = 8). Methods: Horses were randomly assigned into 2 trials: synovitis and no-synovitis. Radiocarpal joint synovitis was induced with lipopolysaccharide 6 hours before IVRLP. IVRLP (5-mg/kg amikacin qs 60 mL) was performed with a pneumatic tourniquet under general anesthesia. Synovial fluid was obtained before and...
Goodwin WA, Keates HL, Pasloske K, Pearson M, Sauer B, Ranasinghe MG.To determine the pharmacokinetics and pharmacodynamics of the neurosteroidal anaesthetic, alfaxalone, in horses after a single intravenous (IV) injection of alfaxalone, following premedication with acepromazine, xylazine and guaiphenesin. Methods: Prospective experimental study. Methods: Ten (five male and five female), adult, healthy, Standardbred horses. Methods: Horses were premedicated with acepromazine (0.03 mg kg(-1) IV). Twenty minutes later they received xylazine (1 mg kg(-1) IV), then after 5 minutes, guaiphenesin (35 mg kg(-1) IV) followed immediately by IV induction of anaesthesia w...
Marshall JF, Blikslager AT.Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in the management of pain and endotoxaemia associated with colic in the horse. While NSAIDs effectively treat the symptoms of colic, there is evidence to suggest that their administration is associated with adverse gastrointestinal effects including right dorsal colitis and inhibition of mucosal barrier healing. Several studies have examined the pathophysiology of NSAID associated effects on the large and small intestine in an effort to avoid these complications and identify effective alternative medications. Differences in the re...
Morton AJ, Varney CR, Ekiri AB, Grosche A.N-butylscopolammonium bromide (NBB) and xylazine are commonly used medications for the treatment of spasmodic colic and other forms of abdominal pain in horses. Both NBB and xylazine exert significant effects on the cardiovascular system and other vital systems of horses. Objective: To evaluate the effects of i.v. administration of NBB, xylazine, and the combination of NBB and xylazine on heart rate, other commonly measured physiological parameters, cardiac rhythm and blood pressure. Methods: Six mature horses of mixed breed were used. In a random cross-over design, each horse was given 0.3 mg...
Turkan F, Harbi Calimli M, Akgun A, Gulbagca F, Sen F.Benzimidazoles are antiparasitic drugs having an extensive application field like agriculture, medicine, and especially in veterinary medicine. In this study, we report the effect of some benzimidazole drugs such as ricobendazole (RBZ), thiabendazole (TBZ), albendazole (ALBA) and oxfendazole (OFZ) on glutathione s-transferase (GST) enzyme activity. The kinetics studies, IC and Ki values of the tested drugs on GSTs enzyme activity were investigated. The obtained ranking of IC values were found to be approximately RBZ (53.31 μM, r 0.9778) < OFZ (57.75 μM, r 0.9630) < ALBA (63.00 μM, r 0...
Törneke K, Ingvast-Larsson C, Pettersson K, Bergvall K, Hedeland M, Bondesson U, Broström H.Clemastine is an H1 antagonist used in certain allergic disorders in humans and tentatively also in horses, although the pharmacology of the drug in this species has not yet been investigated. In the present study we determined basic pharmacokinetic parameters and compared the effect of the drug measured as inhibition of histamine-induced cutaneous wheal formation in six horses. The most prominent feature of drug disposition after intravenous dose of 50 microg/kg bw was a very rapid initial decline in plasma concentration, followed by a terminal phase with a half-life of 5.4 h. The volume of d...
Hardefeldt LY, Crabb HK, Bailey KE, Gilkerson JR, Billman-Jacobe H, Browning GF.Appropriate dosing with antimicrobial agents is critical for effective treatment and to prevent the development of antimicrobial resistance. Methods: A review was undertaken of equine journal articles (Equine Veterinary Journal, Equine Veterinary Education, Australian Veterinary Journal, Australian Equine Veterinarian, Journal of Veterinary Internal Medicine and Journal of Equine Veterinary Science) between January 2015 and August 2018. Those with dosing regimens for procaine penicillin G, gentamicin or trimethoprim-sulfonamide in adult horses were examined and evaluated. Pharmacokinetics and ...
Stojan J.Highly efficient and rapid lead compound evaluation for estimation of inhibition parameters and type of inhibition is proposed. This is based on a single progress-curve measurement in the presence of each candidate compound, followed by the simultaneous analysis of all of these curves using the ENZO enzyme kinetics suite, which can be implemented as a web application. In the first step, all of the candidate ligands are tested as competitive inhibitors. Where the theoretical curves do not correspond to the experimental data, minimal additional measurements are added, with subsequent processing ...
Knych HK, Weiner D, Harrison L, McKemie DS.Intra-articular corticosteroids, such as isoflupredone acetate, are commonly used in the treatment of joint inflammation, especially in performance horses. Following administration in a non-inflamed joints blood concentrations of isoflupredone were low and detectable for only a short period of time post-administration compared to synovial fluid concentrations. For some drugs, inflammation can affect pharmacokinetics, therefore, the goal of the current study was to describe the pharmacokinetics of isoflupredone acetate following intra-articular administration using a model of acute synovitis. S...
Delatour P, Benoit E, Bourdin M, Gobron M, Moysan F.After the administration of racemic ketoprofen and carprofen to man, both enantiomers of each compound exhibit similar plasma profiles. This contrasts with the rat where the active S(+) enantiomer is predominant. For carprofen, regardless of the route of administration, the R(-) enantiomer is predominant in the plasma of all investigated animal species. The S(+)/R(-) ratio of the "areas under the curves" during the time course of the kinetics, is: 0.60 in dogs, 0.53 in Yucatan micro-pigs, 0.48 in mini-goats, 0.67 in calves and 0.19 in horses. For ketoprofen, the S(+) enantiomer is predominant ...
Kang M, Lee S, Seo JP, Lee EB, Ahn D, Shin J, Paik YK, Jo D.The use of the FDA-approved osteoinductive growth factor BMP2 is widespread for bone regeneration. However, its clinical application has been hindered by limitations in cell permeability and a short half-life in circulation. To address this issue, we have developed a modified version of BMP2, referred to as Cell Permeable (CP)-BMP2, which possesses improved cell permeability. CP-BMP2 incorporates an advanced macromolecular transduction domain (aMTD) to facilitate transfer across the plasma membrane, a solubilization domain, and recombinant human BMP2. Compared to traditional rhBMP2, CP-BMP2 ex...
Kamerling S, Weckman T, Donahoe J, Tobin T.Current opiate receptor theory suggests that kappa agonists should provide good analgesia without producing marked central nervous system stimulation. U-50,488H is an experimental narcotic analgesic that is a selective kappa agonist. In the present study, U-50,488H produced good analgesia in horses using both the skin twitch and hoof withdrawal reflex assays. Further, the analgesia was relatively long lasting (120 mins) compared to other mu-agonists tested in horses. The locomotor response to U-50,488H was less than observed with ethylketazocine and butorphanol, and has yielded the smallest lo...
Taylor PM, Browning AP, Harris CP.Combinations of detomidine (mean dose rate 13 micrograms/kg) and butorphanol (mean dose rate 26 micrograms/kg) were used to sedate 61 horses for a variety of surgical or diagnostic procedures in general equine practice. Three horses were sedated on more than one occasion. The degree of sedation was graded from 3 to 0 (deep sedation to no effect) and any side effects were recorded. Forty-three per cent of the horses were graded 3, 46 per cent were graded 2, 8 per cent were graded 1 and 3 per cent were graded 0. Bradycardia and ataxia were the major side effects. The combination was judged to be...
Moore BR.Interferons are efficacious therapeutic agents for treatment of several clinically important diseases in cattle and horses. In some instances, the therapeutic goal of IFN administration is prevention or clinical cure of acute viral infections. On the other hand, IFN may serve as adjunctive treatment to diminish clinical manifestations of disease and improve the quality of life. Oral administration of IFN alpha appears to be a safe and convenient route of administration, and the therapeutic benefit likely develops via unique mechanisms involving oropharyngeal-associated lymphoid tissue for diss...
Foreman JH, Ruemmler R.There are no peer reviewed, blinded controlled studies regarding the skeletal analgesic efficacy of intramuscularly administered meperidine in horses. Objective: Using an adjustable heart bar shoe model of equine foot pain, the objective of this study was to test the hypothesis that meperidine (pethidine) administered intramuscularly would prove more efficacious in alleviating lameness than a saline placebo. Methods: Crossover pharmacodynamic experiment. Methods: Eight healthy adult Thoroughbred horses randomly underwent weekly i.m. treatments 1 h after lameness induction: saline placebo (1â...
Knych HK, Corado CR, McKemie DS, Steffey EP.Both the potential analgesic effect and the conflicting reports describing tramadol disposition in the horse warrant further study of the pharmacokinetics of tramadol in this species. Objective: To describe the pharmacokinetics of tramadol and its metabolites, O-desmethyltramadol and N-desmethyltramadol, following i.v. administration of 3 doses to the horse. Methods: Nine adult horses received a single i.v. dose of 0.5, 1.5 and 3 mg/kg bwt tramadol. Blood samples were collected prior to and at various times up to 72 h post administration. Plasma samples were analysed using liquid chromatograph...
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...
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...
Nieto JE, Maher O, Stanley SD, Knych HK, Snyder JR.To determine the pharmacokinetics, pharmacodynamics, and safety of zoledronic acid in horses. Methods: 8 healthy horses. Methods: A single dose of zoledronic acid (0.057 mg/kg, IV) was administered during a 30-minute period. Venous blood was collected at several time points. Zoledronic acid concentration in plasma was measured by liquid chromatography-tandem mass spectrometry, and pertinent pharmacokinetic parameters were determined. Plasma was analyzed for total calcium, BUN, and creatinine concentrations and a marker for bone resorption (C-terminal telopeptides of type I collagen). Results: ...
Knych HK, Mama KR, Steffey EP, Stanley SD, Kass PH.OBJECTIVE To measure concentrations of trazodone and its major metabolite in plasma and urine after administration to healthy horses and concurrently assess selected physiologic and behavioral effects of the drug. ANIMALS 11 Thoroughbred horses enrolled in a fitness training program. PROCEDURES In a pilot investigation, 4 horses received trazodone IV (n = 2) or orally (2) to select a dose for the full study; 1 horse received a vehicle control treatment IV. For the full study, trazodone was initially administered IV (1.5 mg/kg) to 6 horses and subsequently given orally (4 mg/kg), with a 5-week ...
Broadstone RV, Gray PR, Robinson NE, Derksen FJ.The effect of IV administration of the alpha 2-adrenoceptor agonist xylazine hydrochloride (0.5 mg/kg of body weight) was examined in ponies with recurrent obstructive pulmonary disease, commonly called heaves. Six ponies with the disease (principals) were studied during clinical remission and during an acute attack of airway obstruction precipitated by stabling and feeding of dusty hay. Six control ponies were also studied. In principal ponies with airway obstruction, xylazine administration significantly (P < 0.05) decreased pulmonary resistance and increased dynamic compliance, but did n...
Bergan T, Versland I.To be active, antimicrobials must reach the bacteria in the infectious foci in adequate concentrations. Direct measurements of levels in the various foci are difficult to perform, but a number of animal models with artificial extravascular foci have been developed. In many ways, the physiology of pigs resemble that of humans. Consequently, it was thought that pigs might also parallel humans in the handling of penicillins. General pharmacokinetics of ampicillin and flucloxacillin and the penetration of the substances to subcutaneously implanted teflon tistisue chambers were investigated. Ampici...
Snow DH.Using adrenergic agonists and antagonists this study has demonstrated that adrenaline induced sweating is mediated via beta2-adrenoreceptors in the horse.
Simonsen U, Prieto D, Hernández M, Sáenz de Tejada I, GarcÃa-Sacristán A.The receptors mediating the contractions to both exogenously applied noradrenaline and electrical field stimulation (EFS) were characterized in horse isolated penile resistance arteries. The alpha 1-adrenoceptor-selective antagonist, prazosin, caused competitive rightward shifts of the contractile concentration-response curves (CRC) to phenylephrine. The alpha 2-antagonist, rauwolscine, also displaced to the right the CRC to the alpha 2-adrenoceptor-selective agonist, BHT 920. EFS (0.3 ms, 20-second trains) caused tetrodotoxin-sensitive frequency-dependent contractions which were enhanced in t...
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 ...
Alonso BB, La Rosa L, Carregaro AB, Gasthuys F, Schauvliege S.To examine the influence of detomidine or romifidine on recovery quality from isoflurane anesthesia, 78 anesthetic records were reviewed, from horses that had received romifidine (group R) during premedication [80-120 μg kg IV], anesthetic maintenance (40 μg kg hour IV), and recovery (20 μg kg IV) or detomidine (group D), at doses of 10-20 μg kg IV, 5 μg kg hour IV, and 2.5 μg kg IV, respectively. Duration of the different recovery phases, the number of attempts to sternal and standing, scores for transition to standing (TrSta), balance and coordination once standing (BC), and fina...
Ringer SK, Schwarzwald CC, Portier K, Mauch J, Ritter A, Bettschart-Wolfensberger R.The aim of the present study was to investigate changes in blood glucose concentration ([Glu]B), acid-base status and electrolyte concentrations during constant rate infusions (CRI) of two alpha2-adrenergic agonists in seven horses treated in a blinded, randomised, crossover design with xylazine or romifidine. An intravenous (IV) bolus of xylazine (1mg/kg) or romifidine (80 μg/kg) was administered followed by an IV CRI of xylazine (0.69 mg/kg/h) or romifidine (30 μg/kg/h) for 2h. Blood samples were collected from the pulmonary artery before and after loading doses, during the CRI, and for 1h...
Broux B, De Clercq D, Decloedt A, Vera L, Devreese M, Gehring R, Croubels S, van Loon G.Arrhythmias in horses may require long-term anti-arrhythmic therapy. Unfortunately, oral anti-arrhythmic drugs for use in horses are currently scarce. In human patients and small animals, sotalol, a β-blocker with class III anti-arrhythmic properties, is often used for long-term treatment. Objective: To determine the pharmacokinetics of sotalol at multiple oral dosages in unfasted horses, as well as the effects on electro- and echocardiographic measurements, right atrial and ventricular monophasic action potential (MAP) and effective refractory period (ERP). Methods: Placebo controlled, doubl...