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.
Crosignani N, Luna SP, Dalla Costa T, Pimenta EL, Detoni CB, Guterres SS, Puoli Filho JN, Pantoja JC, Pigatto MC.We investigated the thermal, electrical and mechanical antinociceptive and physiological effects (heart rate, respiratory rate, arterial blood pressure, head height and abdominal auscultation score), and pharmacokinetics, of 0.5 mg/kg of the injectable formulation (ORAL) or nanoparticulated methadone (NANO) given orally, in six adult mares, using a crossover, blind and prospective design. Repeated-measure models were used to compare parametric data between and within treatments, followed by Tukey's test. Nonparametric data were analysed with Wilcoxon signed-rank, adjusted by Bonferroni tests....
Edwards SH, Khalfan SA, Jacobson GA, Pirie AD, Raidal SL.OBJECTIVE To determine plasma drug concentrations after IV administration of a bolus followed by continuous rate infusion (CRI) of sodium benzylpenicillin and ceftiofur sodium to healthy adult horses. ANIMALS 6 Thoroughbred mares (3 to 9 years old; mean ± SD body weight, 544 ± 55 kg) with no history of recent antimicrobial treatment. PROCEDURES Horses were used in 2 experiments conducted 14 days apart. For each experiment, horses were housed individually in stables, and catheters were placed bilaterally in both jugular veins for drug administration by CRI (left catheter) and for intermittent...
Ramsay EC, Geiser D, Carter W, Tobin T.To compare the effect of orally delivered detomidine on head posture when administered alone or in combination with two different food items, and to determine the serum concentrations of detomidine after oral delivery. Methods: Prospective randomized experimental study. Methods: Fifteen adult grade mares weighing 328-537 kg. Methods: The horses were randomly assigned to one of the three treatment groups (five horses each). The groups were given detomidine (0.06 mg kg): alone; mixed with 3 mL of an apple sauce and gum mixture; or mixed with 3 mL molasses. Head droop, measured before treatment a...
Machnik M, Kaiser S, Koppe S, Kietzmann M, Schenk I, Düe M, Thevis M, Schänzer W, Toutain PL.Methylxanthines positives in competition samples have challenged doping control laboratories and racing jurisdictions since methylxanthines are naturally occurring prohibited substances and often constituents of feed. For theobromine, an international threshold (renamed in International Residue Limit, IRL) of 2 µg/mL in urine has been established. On the basis of the data presented herein, a threshold or rather an IRL for theobromine in plasma of 0.3 µg/mL was proposed and was thereupon approved by the International Federation of Horseracing Authorities (IFHA). Official recommendations f...
Burkett BN, Thomason JM, Hurdle HM, Wills RW, Fontenot RL.Determine the effects of nonsteroidal anti-inflammatory drugs (NSAID) on platelet function and thromboxane synthesis immediately after drug administration and following 5 days of NSAID administration in healthy horses. Methods: Randomized cross-over study. Methods: Healthy adult horses (n=9; 6 geldings and 3 mares). Methods: Horses received either flunixin meglumine (1.1 mg/kg IV every 12 hours), phenylbutazone (2.2 mg/kg IV every 12 hours), or firocoxib (loading dose of 0.27 mg/kg IV on day 1, then 0.09 mg/kg IV every 24 hours for 4 days) for a total of 5 days. Blood samples were collected pr...
Rodríguez-Pozo ML, Armengou L, Monreal L, Viu J, Cesarini C, Jose-Cunilleras E.To assess whether an oral direct factor Xa inhibitor (DiXaI) anticoagulant drug used at the low end of the recommended dose in people achieves presumed prophylactic plasma concentrations and does not induce bleeding in horses. Methods: Experimental study. Methods: Field study. Methods: Ten healthy adult horses. Methods: A DiXaI was administered at a dose of 0.125 mg/kg every 24 h orally for 4 days. Following a wash-out period of 2 weeks, 8 of 10 horses received daily subcutaneous doses of a low molecular weight heparin (dalteparin) for 4 consecutive days at 50 IU/kg. In both trials, antifactor...
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...
Guan F, Robinson MA, Soma LR.Etanercept is a protein-based medication for the treatment of human patients with rheumatoid arthritis and other autoimmune-based diseases; its pharmacological action is to inhibit and antagonize tumour necrosis factor alpha. Etanercept was rumoured to be used in horse racing in North America. To detect such use, the aim of this study was to develop a liquid chromatography-mass spectrometry (LC-MS) method for confirmation of etanercept in equine plasma. Etanercept was extracted from plasma by anti-human IgG antibody linked to magnetic beads. The analyte was reduced and alkylated, and then dige...
Saes IL, Vera JHS, Fachiolli DF, Yamada PH, Dellaqua JVT, Saes RL, Amarante AFT, Soutello RVG.The aim of this study was to determine the time required by different anthelmintic agents to reduce strongyle egg shedding in horses. Fifty horses were divided into five homogenous groups based on faecal egg counts (FECs). Treatment groups received either ivermectin; moxidectin; fenbendazole; piperazine; or no treatment (control group). Faecal examinations were performed 4, 8, 12, 18, 24, 36 and 48h after the anthelmintic treatment. After this period, faecal samples were taken every 24h over the next 12days and finally on alternate days (48-h intervals) for another 14days until the end of the ...
Sykes BW, Underwood C, Greer R, McGowan CM, Mills PC.Conflicting data are presented in the current literature regarding the efficacy of omeprazole for suppressing gastric acidity in the horse. Objective: The objective of this study was to investigate the duration of intraday acid suppression achieved with two doses of omeprazole under two different dietary conditions. Methods: A four-way crossover design. Methods: Six adult Thoroughbred horses instrumented with percutaneous gastrotomy tubes were used. Intragastric pH was measured for continuous 23 h periods (08.00-07.00 h) for six consecutive days (Days 0-5). Baseline data was recorded on Day 0 ...
Epstein KL, Bergren A, Nie B, Arnold RD, Brainard BM.A lower molecular weight and molar substitution formulation (130/0.4) of hydroxyethyl starch solution has been shown to have a more sustained effect on COP and similar hemodynamic effects as a higher molecular weight and molar substitution formulation (600/0.75) in healthy horses. In humans, these pharmacodynamic characteristics are coupled with more rapid clearance and decreased adverse coagulation effects and accumulation. The objective of this study was to determine and compare the pharmacokinetics of these two formulations in horses. Eight healthy horses were given a 10 mL/kg bolus of eac...
Uney K, Altan F, Altan S, Erol H, Arican M, Elmas M.The plasma and synovial fluid pharmacokinetics and safety of cefquinome, a 2-amino-5-thiazolyl cephalosporin, were determined after multiple intravenous administrations in sixteen healthy horses. Cefquinome was administered to each horse through a slow i.v. injection over 20 min at 1, 2, 4, and 6 mg/kg (n = 4 horses per dose) every 12 h for 7 days (a total of 13 injections). Serial blood and synovial fluid samples were collected during the 12 h after the administration of the first and last doses and were analyzed by a high-performance liquid chromatography assay. The data were evaluate...
Knych HK, Stanley SD, McKemie DS, Arthur RM, Kass PH.There is limited data describing xylazine serum concentrations in the horse and no reports of concentrations beyond 24 hours. The primary goal of the study reported here was to update the pharmacokinetics of xylazine following intravenous (IV) administration in order to assess the applicability of current regulatory recommendations. Pharmacodynamic parameters were determined using PK-PD modeling. Sixteen exercised adult Thoroughbred horses received a single IV dose of 200 mg of xylazine. Blood and urine samples were collected at time 0 and at various times for up to 96 hours and analyzed...
Wetmore LA, Pascoe PJ, Shilo-Benjamini Y, Lindsey JC.OBJECTIVE To determine the locomotor response to the administration of fentanyl in horses with and without the G57C polymorphism of the μ-opioid receptor. ANIMALS 20 horses of various breeds and ages (10 horses heterozygous for the G57C polymorphism and 10 age-, breed-, and sex-matched horses that did not have the G57C polymorphism). PROCEDURES The number of steps each horse took was counted over consecutive 2-minute periods for 20 minutes to determine a baseline value. The horse then received a bolus of fentanyl (20 μg/kg, IV), and the number of steps was again counted during consecutive 2-...
Kooyman FN, van Doorn DC, Geurden T, Mughini-Gras L, Ploeger HW, Wagenaar JA.For the control of cyathostomins in horses, the macrocyclic lactones (MLs), moxidectin (MOX) and ivermectin (IVM) are the most commonly used anthelmintics. However, reduced activity, observed as shortening of the egg reappearance period (ERP) has been described. Shortening of the ERP may be caused by a decreased susceptibility of immature worms for MLs. Alternatively, immature worms may develop faster into egg producing adults as a result of repeated ML treatments. The species composition of the larval cultures obtained shortly after ML and pyrantel (PYR) treatment can confirm the hypothesis o...
Afonso T, Giguère S, Rapoport G, Brown SA, Coleman AE.Benazepril has been shown to inhibit circulating angiotensin-converting enzyme (ACE) activity in horses but the optimal dosage is unknown. Objective: To determine the lowest tested dose of benazepril that results in ≥75% attenuation in the response of arterial blood pressure (BP) to exogenous angiotensin I (ANG-I) administration. Methods: Prospective experimental study. Methods: A total of 5 healthy horses were instrumented for the direct measurement of BP. Each horse received 4 intragastric doses of benazepril (0.5, 1, 2 and 4 mg/kg bwt) with a washout period of 7 days between doses. Prior ...
McConaghy FF, Green LA, Colgan S, Morris LH.To investigate the efficacy and safety of the long-acting altrenogest injection (NV Readyserve® injection) for horses. Methods: A single-dose pharmacokinetic (PK) study was conducted. The in vivo efficacy study was a blinded, repeated measures design evaluating behaviour scores. The safety study was a non-blinded, controlled, parallel-group, randomised-block design as per the VICH protocol. Methods: In the PK study, serial blood samples were obtained for analysis of plasma altrenogest for 150 h following the injection and a non-compartmental PK analysis was performed. For the efficacy study, ...
McFarlane D, Banse H, Knych HK, Maxwell LK.The objective of this study was to gain an understanding of the pharmacokinetic and pharmacodynamic properties of pergolide in horses with PPID after of long-term oral administration. Six horses with confirmed PPID were treated with pergolide (Prascend ) at 1 mg/horse po q24 h for 2 months, followed by 2 mg/horse po q24 h for 4 months. Following the last dose, plasma samples were collected for measurement of pergolide using an LC/MS/MS method and ACTH measurement using a chemiluminescent immunoassay. Noncompartmental and compartmental pharmacokinetic analyses were performed, as well as p...
Arroyo MG, Couëtil LL, Nogradi N, Kamarudin MM, Ivester KM.The (R)-enantiomer of racemic albuterol (levalbuterol) has bronchodilatory properties whereas the (S)-enantiomer causes adverse effects in human airways, animal models, and isolated equine bronchi. Levalbuterol is commercially available and improves pulmonary function of asthmatic patients with a longer duration of effect than albuterol. Objective: To determine the dose at which inhaled levalbuterol produces maximal bronchodilatory effect (EDmax) and determine its duration of action in recurrent airway obstruction (RAO)-affected horses in comparison to racemic albuterol. Methods: Nine horses w...
Oreff GL, Dahan R, Tatz AJ, Raz T, Britzi M, Kelmer G.To determine the influence of 3 perfusate volumes on amikacin concentration in the metacarpophalangeal joint following cephalic regional limb perfusion (RLP) in standing horses. Methods: Seven healthy horses. Methods: Three perfusate volumes (100, 60, and 30 mL), containing 2 grams of amikacin, were tested during intravenous RLP at the cephalic vein, placing the tourniquet at mid antebrachium, in standing sedated horses. Synovial fluid was collected from the metacarpophalangeal joint before perfusion and at 30 and 120 minutes after perfusion. Serum samples were taken from the jugular vein at t...
Godfrey JL, Hardy J, Cohen ND.OBJECTIVE To evaluate the effect of volume of IV regional limb perfusion (IVRLP) on amikacin concentrations in synovial and interstitial fluid of horses. ANIMALS 8 healthy adult horses. PROCEDURES Each forelimb was randomly assigned to receive IVRLP with 4 mL of amikacin sulfate solution (250 mg/mL) plus 56 mL (total volume, 60 mL) or 6 mL (total volume, 10 mL) of lactated Ringer solution. Horses were anesthetized, and baseline synovial and interstitial fluid samples were collected. A tourniquet was placed, and the assigned treatment was administered via the lateral palmar digital vein. Venous...
Knych HK, Steffey EP, White AM, McKemie DS.Tramadol is an analgesic agent used in man and a number of veterinary species. The pharmacokinetics and behavioural effects of tramadol and its active metabolite have been described in mature horses, but not in young foals. Objective: To characterise the pharmacokinetics, metabolism and some induced behavioural and physiological responses following i.v. tramadol administration in the same group of foals on 4 different occasions, from a few days after birth to age 43 days. Methods: Experimental. Methods: Tramadol was administered i.v. (3 mg/kg bwt) to a group of 8 foals on 4 separate occasion...
Knych HK, Stanley SD, Seminoff KN, McKemie DS, Kass PH.Methocarbamol (MCBL) is commonly used in performance horses for the treatment of skeletal muscle disorders. Current regulatory recommendations for show horses and racehorses are based on a single oral dose of 5 g, although doses in excess of this are often administered. The goal of the current study was to characterize the disposition of MCBL following higher dose administration and administration in combination with another commonly used drug in performance horses, phenylbutazone (PBZ). Exercised Thoroughbred horses were administered various doses of MCBL as a sole agent and MCBL in combinat...
de Vries A, Pakkanen SA, Raekallio MR, Ekiri A, Scheinin M, Taylor PM, Vainio OM.To investigate the effects of MK-467 on sedation quality, and cardiopulmonary and pharmacokinetic variables in horses sedated intravenously (IV) with romifidine. Methods: Experimental, randomized, crossover design. Methods: Seven healthy mares. Methods: Romifidine (80 μg kg-1 ; R) and MK-467 (200 μg kg-1 ; MK) were administered IV alone and in combination (R + MK). Levels of sedation and borborygmi were scored. Heart rate (HR), direct arterial blood pressure (ABP) and respiratory rate (fR ) were recorded. Arterial and venous blood gas analyses were performed and venous plasma drug conc...
Gokbulut C, Aksit D, Santoro M, Roncoroni C, Mariani U, Buono F, Rufrano D, Fagiolo A, Veneziano V.Mebendazole (MBZ) has been licensed for use in horses and donkeys, however there are no data available in the literature regarding its pharmacokinetic disposition and efficacy in donkeys. This study was designed to determine the plasma disposition, milk excretion and anthelmintic efficacy of MBZ in donkeys naturally infected by Cyathostominae. The animals were allocated to three groups, each of six donkeys. One group was untreated control (C-group) and the others were treated using a paste formulation of MBZ administered per os at the manufacturer's recommended horse dosage of 10 mg/kg body we...
Aristizabal FA, Nieto JE, Guedes AG, Dechant JE, Yamout S, Morales B, Snyder J.Regional limb perfusion (RLP) in horses has proven to be a simple and effective technique for the treatment of synovial and musculoskeletal infections in the distal portion of the limbs. The ideal tourniquet time needed to achieve therapeutic synovial concentrations remains unknown. The pharmacokinetic effects of general anesthesia (GA) versus standing sedation (SS) RLP on synovial amikacin concentrations are not completely understood. This study investigated the pharmacokinetic effects of RLP under general anesthesia (GA) versus standing sedation (SS) on synovial amikacin concentration follow...
Ekstrand C, Ingvast-Larsson C, Olsén L, Hedeland M, Bondesson U, Gabrielsson J.The cortisol response to glucocorticoid intervention has, in spite of several studies in horses, not been fully characterized with regard to the determinants of onset, intensity and duration of response. Therefore, dexamethasone and cortisol response data were collected in a study applying a constant rate infusion regimen of dexamethasone (0.17, 1.7 and 17 μg/kg) to six Standardbreds. Plasma was analysed for dexamethasone and cortisol concentrations using UHPLC-MS/MS. Dexamethasone displayed linear kinetics within the concentration range studied. A turnover model of oscillatory behaviour accu...
Autefage A, Alvinerie M, Toutain PL.Synovial fluid and plasma kinetics of methylprednisolone acetate (MPA) and methylprednisolone (MP) after a single intra-articular administration of MPA at a therapeutic dose (111 mg in toto) was measured in five horses. MPA was detected in synovial fluid for two to six days post injection and MP, which results from synovial MPA hydrolysis, was present in pharmacologically significant concentrations for 4.8 to 39 days, depending on the horse. MPA synovial concentration was maximal (289 +/- 284 micrograms/ml) at the first sampling time (2 h after administration) and MP synovial concentration was...
Winther L, Guardabassi L, Baptiste KE, Friis C.Sulfadiazine (SDZ) and trimethoprim (TMP) concentrations were examined in plasma and pulmonary epithelial lining fluid (PELF), following intravenous and oral administration and compared to minimum inhibitory concentrations (MICs) of common bacterial isolates from equine lower airway infections. SDZ/TMP (25/5 mg/kg) was administered intravenously, intragastric or per os to fed horses, and blood samples were collected before and 11 times, over 24 h, after administration. PELF samples were collected via a tampon device four times after drug administration and analysed for drug concentrations. Add...
Hall TL, Tell LA, Wetzlich SE, McCormick JD, Fowler LW, Pusterla N.Ceftiofur, a third generation cephalosporin, demonstrates in vitro efficacy against microorganisms isolated from septicemic neonatal foals. This pharmacokinetic study evaluated the intravenous and subcutaneous administration of ceftiofur sodium (5 mg/kg body weight; n = 6 per group) and subcutaneous administration of ceftiofur crystalline free acid (6.6 mg/kg body weight; n = 6) in healthy foals. Plasma ceftiofur- and desfuroylceftiofur-related metabolite concentrations were measured using high performance liquid chromatography following drug administration. Mean (±SD) noncompartmental pharma...
Broome TA, Brown MP, Gronwall RR, Casey MF, Meritt KA.Six healthy adult horses (5 mares and 1 stallion) were given a single dose of acetylsalicylic acid (ASA), 20 mg/kg of body weight, by intravenous (IV), rectal, and intragastric (IG) routes. Serial blood samples were collected via jugular venipuncture over a 36-h period, and plasma ASA and salicylic acid (SA) concentrations were determined by high-performance liquid chromatography. After IV administration, the mean elimination rate constant of ASA (+/- the standard error of the mean) was 1.32 +/- 0.09 h(-1), the mean elimination half-life was 0.53 +/- 0.04 h, the area under the plasma concentra...
Swanson CR, Muir WW, Bednarski RM, Skarda RT, Hubbell JA.The hemodynamic changes induced by constant infusions of dopamine or dobutamine (each 3, 5, and 10 micrograms/kg/min) were observed in halothane-anesthetized horses. Left ventricular dp/dt and cardiac output were increased in horses given dobutamine at dosage of 3 micrograms/kg/min and in those given either of the drugs at dosages of 5 and 10 micrograms/kg/min. Concomitant increases in systemic arterial blood pressure occurred at lower infusion dosage rates of dobutamine than those of dopamine and were modulated by dosage-related changes in peripheral vascular resistance that were different be...
Chen CL, Sailor JA, Collier J, Wiegand J.Seven mature thoroughbred horses, weighing between 400 and 541 kg, were each injected intra-articularly into three joints with 6 mg/joint of triamcinolone acetonide (Vetalog). The fourth joint, the control, was injected with saline. Synovial fluid was taken from all four legs of the horses on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following the injections. Triamcinolone acetonide was assayed by a radioimmunoassay. Blood was collected at 1, 2, 4, 6, 12 h and on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following injection of either triamcinolone or saline. Both cortisol and triamcinolone were as...
Ekstrand C, Ingvast-Larsson C, Olsén L, Hedeland M, Bondesson U, Gabrielsson J.The cortisol response to glucocorticoid intervention has, in spite of several studies in horses, not been fully characterized with regard to the determinants of onset, intensity and duration of response. Therefore, dexamethasone and cortisol response data were collected in a study applying a constant rate infusion regimen of dexamethasone (0.17, 1.7 and 17 μg/kg) to six Standardbreds. Plasma was analysed for dexamethasone and cortisol concentrations using UHPLC-MS/MS. Dexamethasone displayed linear kinetics within the concentration range studied. A turnover model of oscillatory behaviour accu...
Carregaro AB, Freitas GC, Ribeiro MH, Xavier NV, Dória RG.Continuous-rate infusion (CRI) of drugs results in more stable plasma drug concentrations than administration of intermittent boluses, thus providing greater stability of physiological parameters. The aim of this study was to evaluate the physiologic and analgesic effects of the administration of morphine, butorphanol, tramadol or methadone by CRI in horses with induced synovitis of the radiocarpal joint. Results: Increased values of cardiorespiratory parameters and body temperature were observed in all groups after initiation of opioid administration, and these increases were sustained throug...
Zhang XY, Zhu FX, Olszewski MA, Robinson NE.The beta 2-agonists currently used as bronchodilators are racemic mixtures of R- and S-enantiomers. In the present study, we examined the effects of enantiomers of the beta 2-agonists albuterol and formoterol on acetylcholine (ACh) release from equine trachealis parasympathetic nerves. ACh release was evoked by electrical field stimulation (20 V, 0.5 ms, 0.5 Hz) and measured by high-performance liquid chromatography coupled with electrochemical detection. We also tested the effects of enantiomers of albuterol and formoterol on equine tracheal smooth muscle (TSM) contraction in response to exog...
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-Mélou A, Formentini E, Picard-Hagen N, Delage L, Laroute V, Toutain PL.The present study aimed to characterize the adrenal response to ACTH. A model was developed that coupled the nonlinear disposition of cortisol with a physiologically based model for cortisol secretion by the adrenals. It was assumed that the response to ACTH resulted from two mechanisms: a stimulation of the cortisol secretion rate and control of the duration of the secretion. Seven dose levels of ACTH were tested in horses, a species similar to man as regards adrenal function. The main result was that the secretion rate of the adrenal gland can be modelized by a zero order process that is max...
Mendoza FJ, Serrano-Rodriguez JM, Perez-Ecija A.Nonsteroidal anti-inflammatory drugs are administered in horses for several systemic diseases. Selective cyclooxygenase-2 inhibitors are preferred because of lower risk of adverse effects. Several meloxicam formulations have been tested in horses, but a recently marketed granule oral formulation has not been studied. Objective: To characterize the pharmacokinetics of a novel granule meloxicam formulation in fasted and fed horses, and to compare pharmacokinetic features with oral suspension and tablets. Methods: Seven healthy adult horses. Methods: Meloxicam was administered at 0.6 mg/kg in fas...
Chapuis RJJ, Smith JS, French HM, Toka FN, Peterson EW, Little EL.Doxycycline (DXC) is a broad-spectrum antibacterial antimicrobial administered to horses for the treatment of bacterial infections which may also affect donkeys. Donkeys have a different metabolism than horses, leading to differences in the pharmacokinetics of drugs compared to horses. This study aimed to describe the population pharmacokinetics of DXC in donkeys. Five doses of DXC hyclate (10 mg/kg) were administered via a nasogastric tube, q12 h, to eight non-fasted, healthy, adult jennies. Serum, urine, synovial fluid and endometrium were collected for 72 h following the first administratio...
Grimsrud KN, Mama KR, Thomasy SM, Stanley SD.Detomidine is commonly used i.v. for sedation and analgesia in horses, but the pharmacokinetics and metabolism of this drug have not been well described. Objective: To describe the pharmacokinetics of detomidine and its metabolites, 3-hydroxy-detomidine (OH-detomidine) and detomidine 3-carboxylic acid (COOH-detomidine), after i.v. and i.m. administration of a single dose to horses. Methods: Eight horses were used in a balanced crossover design study. In Phase 1, 4 horses received a single dose of i.v. detomidine, administered 30 microg/kg bwt and 4 a single dose i.m. 30 microg/kg bwt. In Phase...
Chiavaccini L, Claude AK, Lee JH, Ross MK, Meyer RE, Langston VC.The study objective was to compare butorphanol pharmacokinetics and physiologic effects following intravenous and subcutaneous administration in horses. Ten adult horses received 0.1 mg/kg butorphanol by either intravenous or subcutaneous injections, in a randomized crossover design. Plasma concentrations of butorphanol were measured at predetermined time points using highly sensitive liquid chromatography-tandem mass spectrometry assay (LC-MS/MS). Demeanor and physiologic variables were recorded. Data were analyzed with multivariate mixed-effect model on ranks (P ≤ 0.05). For subcutaneous i...
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...
Kelmer G, Tatz AJ, Famini S, Bdolah-Abram T, Soback S, Britzi M.Regional limb perfusion (RLP) significantly decreases morbidity and mortality associated with distal limb injuries in horses. There is an urgent need for finding additional effective antimicrobial drugs for use in RLP. In this study, we tested the pharmacokinetics (PK) of chloramphenicol in RLP. Eight horses participated in the study, which was approved by the University Animal Care and Use Committee. The cephalic and the saphenous veins were used to perfuse the limbs. Synovial samples were collected from the metacarpo/metatarsophalangeal (MCP/MTP) joint. The Friedman Test was applied for asse...
Knych HK, Arthur RM, Mitchell MM, Holser I, Poppenga R, Smith LL, Helm MN, Sams RA, Gaskill CL.Cobalt has been used by human athletes due to its purported performance-enhancing effects. It has been suggested that cobalt administration results in enhanced erythropoiesis, secondary to increased circulating erythropoietin (EPO) concentrations leading to improvements in athletic performance. Anecdotal reports of illicit administration of cobalt to horses for its suspected performance enhancing effects have led us to investigate the pharmacokinetics and pharmacodynamic effects of this compound when administered in horses, so as to better regulate its use. In the current study, 18 horses were...
Spadavecchia C, Arendt-Nielsen L, Andersen OK, Spadavecchia L, Schatzmann U.To investigate the action of a single IV administration of romifidine on the thresholds of the nociceptive withdrawal reflex (NWR) and temporal summation in conscious horses. Methods: 10 adult horses. Methods: Single electrical stimulations were applied on the digital nerves to evoke NWR from the left forelimb and hind limb. Repeated electrical stimulations (10 stimuli, 5 Hz) were given to obtain temporal summation. Surface electromyographic reflex activity was recorded from the common digital extensor and cranial tibial muscles. After baseline assessment of NWR and temporal summation threshol...
Sun WC, Moore JN, Hurley DJ, Vandenplas ML, Linden JM, Murray TF.To evaluate anti-inflammatory effects of several novel adenosine receptor agonists and to determine their specificity for various adenosine receptor subtypes on neutrophils, cells heterologously expressing equine adenosine receptors, or equine brain membranes. Methods: Neutrophils isolated from 8 healthy horses. Methods: Radioligand binding experiments were performed to compare binding affinities of adenosine receptor agonists to equine adenosine A(1), A(2A), and A(3) receptor subtypes. Effects of these agonists on endotoxin-induced production of reactive oxygen species (ROS) by equine neutrop...
Jean D, Vrins A, Lavoie JP.To determine temporal variations of pulmonary function in horses without respiratory tract disease (controls) and horses with chronic obstructive pulmonary disease (COPD) and determine whether reversibility of airway obstruction after environmental control can be predicted by response to atropine administration. Methods: 7 COPD-affected and 5 control horses. Methods: Pulmonary function testing was performed monthly during 3 consecutive months, daily for 5 consecutive days, and at 6-hour intervals for 24 hours before and after administration of atropine (0.02 mg/kg of body weight, i.v.) and aft...
Uney K, Altan F, Altan S, Erol H, Arican M, Elmas M.The plasma and synovial fluid pharmacokinetics and safety of cefquinome, a 2-amino-5-thiazolyl cephalosporin, were determined after multiple intravenous administrations in sixteen healthy horses. Cefquinome was administered to each horse through a slow i.v. injection over 20 min at 1, 2, 4, and 6 mg/kg (n = 4 horses per dose) every 12 h for 7 days (a total of 13 injections). Serial blood and synovial fluid samples were collected during the 12 h after the administration of the first and last doses and were analyzed by a high-performance liquid chromatography assay. The data were evaluate...
Soma LR, Uboh CE, Luo Y, Guan F, Moate PJ, Boston RC.To determine the pharmacokinetics of methylprednisolone (MP) and develop a pharmacokinetic-pharmacodynamic model of the related changes in plasma concentrations of endogenous hydrocortisone (HYD) and cortisone (COR) following intra-articular administration of methylprednisolone acetate (MPA) in horses. Methods: 6 Thoroughbreds. Methods: In each horse, 200 mg of MPA was injected intrasynovially into a carpal joint, and plasma MP, HYD, and COR concentrations were determined via liquid chromatography-mass spectrometry. Results: A 5-compartment pharmacokinetic-pharmacodynamic model was used to des...
Bijman J, Quinton PM.Single equine sweat glands were found to secrete for more than 1 h in vitro in response to pharmacologic secretagogues. The adrenergic agonists epinephrine and norepinephrine evoked maximal sweat rates of 2.0 nl X gland-1 X min-1. However, the concentration of norepinephrine (10(-5) M) required to evoke the maximal response was 10 times higher than that for epinephrine. Maximal sweat rates also were stimulated with the beta 2-adrenergic agonist terbutaline. This stimulation was blocked by the beta-adrenergic antagonist propranolol. Moderate sweating responses were also obtained with the alpha-...
Guedes A, Knych H, Tucker L, Almeida DC, Baldo CF, Wendt-Hornickle E, Allweiler S.This study determined the pharmacokinetics and compared the clinical effects of xylazine and dexmedetomidine in horses recovering from isoflurane anesthesia. Six healthy horses aged 8.5 ± 3 years and weighing 462 ± 50 kg were anesthetized with isoflurane for 2 hr under standard conditions on two occasions one-week apart. In recovery, horses received 200 μg/kg xylazine or 0.875 μg/kg dexmedetomidine intravenously and were allowed to recover without assistance. These doses were selected because they have been used for postanesthetic sedation in clinical and research studies. Serial ...
Santonastaso A, Hardy J, Cohen N, Fajt V.In certain situations, an alternate route for parenteral drug administration in horses may be useful. The intra-osseous (IO) route may provide a safe alternative to the intravenous (i.v.) route for administration of sedatives to horses when the i.v. route is inaccessible or undesirable. Six adult horses were administered xylazine i.v. or IO in a block-randomized crossover design. For the i.v. trial, both jugular veins were catheterized, and one was used for xylazine administration, while the other was used for blood collection. For the IO trial, one jugular vein was catheterized for blood coll...
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 ...
Moore RM, Sedrish SA, Holmes EP, Koch CE, Venugopal CS.The objective of this study was to determine and compare the in vitro responses of equine large colon arterial and venous rings to vasodilatory neuropeptides; calcitonin gene-related peptide (CGRP); substance P (SP); vasoactive intestinal polypeptide (VIP); and acetylcholine (ACh), a standard nonpeptide endothelium-dependent vasodilator. Responses of vessel rings to graded concentrations (10(-11) M to 10(-5) M) of each drug were determined in endothelium-intact, denuded, and Nomega-nitro-L-arginine methyl ester (L-NAME, 10(-5) M)-treated rings that were pre-contracted with norepinephrine. Perc...
Lyons ET, Tolliver SC, Collins SS.Population B, drug-resistant small strongyles have been studied in naturally infected horses in Kentucky for more than 40 years. These parasites first were found to be resistant to phenothiazine (PTZ) and thiabendazole (TBZ), later to other parasiticides. Studies have been on evaluation of antiparasitic efficacy of several compounds, especially the benzimidazoles, against Population B small strongyles in clinical (field) tests (1959-1983) on the commercial farm of origin and in clinical and critical tests (1966-2001) at the University of Kentucky (UK) research farm. Research on these nematodes...
Eyre P, Elmes PJ, Strickland S.Spirally cut digital arteries and veins were mounted isotonically in organ baths containing oxygenated Krebs' Q-Henseleit solution. Twelve arterial and 12 venous preparations all contracted dose dependently when epinephrine, norepinephrine, serotonin, or histamine were added to the bathing fluid. Addition of hydrocortisone or betamethasone alone did not cause contractions in any of the tissues tested. However, when hydrocortisone or betamethasone was added to vessel strips that were partially contracted (40% to 60% maximal) by epinephrine, norepinephrine, or serotonin, each vessel strip invari...
