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.
Kodaira K, Kakizaki M, Nagata SI, Ode H, Okano A, Tamura N, Mizobe F, Matsuda Y, Kurimoto S, Aida H.To investigate the pharmacodynamics and pharmacokinetics of rocuronium administered by bolus injection to sevoflurane-anesthetized horses. Methods: Prospective, experimental, crossover study. Methods: Five healthy adult Thoroughbred horses (body mass 368-470 kg, three females and two males). Methods: Each horse was anesthetized twice with sevoflurane and assigned to be administered rocuronium bromide intravenously: 0.2 mg kg (R02) or 0.4 mg kg (R04). There was a minimum 2 week washout period between experiments. During anesthesia, the peroneal nerve was stimulated (train-of-four) and neuromusc...
Wong AM, Schier MF, Hosgood G, Drynan E, Raisis AL.To explore the influence of acepromazine on the cardiovascular effects of dobutamine in isoflurane-anaesthetised horses premedicated with romifidine. Methods: Prospective randomised clinical trial. Methods: A total of 18 horses undergoing elective arthroscopy were enrolled, of which 12 horses requiring dobutamine were included. Methods: Horses were randomised to receive acepromazine 0.02 mg kg (Group A+) intravenously (IV) or none (Group A-), 35 minutes before anaesthesia. Horses received xylazine 0.2 mg kg concurrently to facilitate IV access. Horses were premedicated with romifidine 0.08 mg ...
Lehman ML, Domenig O, Ames MK, Morgan JM.Furosemide, a commonly used diuretic, activates the renin-angiotensin-aldosterone system (RAAS) in other species. Little is known about RAAS peptide activation in horses. Objective: To evaluate equilibrium analysis as a practical method for RAAS quantification in horses and describe the RAAS response to a single dose of furosemide. We hypothesize that furosemide would cause transient increase in RAAS peptides in horses. Methods: 14 healthy adult thoroughbreds from a university teaching herd. Methods: Horses received either furosemide (1 mg/kg IV) or saline IV in a crossover study design. Pro...
Galinelli NC, Bamford NJ, Erdody ML, Warnken T, de Laat MA, Sillence MN, Harris PA, Bailey SR.Alpha-methyl-para-tyrosine (AMPT) is a reversible inhibitor of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. This study aimed to determine whether AMPT could reduce dopamine concentrations in horses. Six healthy adult Standardbred geldings were administered AMPT (40 mg/kg BW, orally) or placebo in a randomised crossover study design. Clinical examination findings were recorded, and blood samples were collected for up to 6 h after administration of AMPT or placebo, for measurement of blood glucose, plasma ACTH and cortisol concentrations, and plasma metabolomic anal...
Knych HK, Steinmetz SJ, Traynham ML, McKemie DS, Kass PH.Morphine is an effective analgesic in horses, however, IV administration at therapeutic doses has been shown to produce dose-dependent neuroexcitation and unwanted gastrointestinal effects. The analgesic effects of morphine have, at least in part, been attributed to the morphine-6-glucuronide (M6G) metabolite. Oral administration to horses results in comparable M6G concentrations to that achieved following IV administration of a therapeutic dose without the adverse effects. The anti-nociceptive effects have not yet been reported. In the current study the thermal anti-nociceptive effects of sin...
Knych HK, Blea J, Scollay M, Kass PH, McKemie DS.Ethanol, a central nervous system depressant and banned substance in horseracing, has reportedly been administered to horses prior to competition to "calm a horse's nerves." In this study, the pharmacokinetics of two metabolites of ethanol were studied to better understand the behavior of this compound in the horse and provide a scientific basis for regulation of its administration. Six horses received a single intravenous (30 mL; 1200 mg) and oral (90 mL; 3600 mg) administration of ethanol (vodka, 40% ABV) in a balanced cross-over design. Blood and urine samples were collected at vari...
Swanton WE, Johnson R, Zhao Q, Schroeder C.To evaluate sedation and IV xylazine requirements to achieve 45% of baseline head height above ground measurements following oral (PO) administration of 2 trazodone dosages. Methods: 8 healthy, adult mares of various weights and breeds belonging to a university teaching herd were utilized in a blinded, crossover study design. Horses were randomly assigned to 1 of 3 PO treatments: control (no trazodone), trazodone at 3 mg/kg (low dose [LD]), or trazodone at 6 mg/kg (high dose [HD]). Before treatment, cardiac auscultation, EquiSed sedation score, and head height above ground (HHAG; cm) measureme...
McCarrel TM, Cole C, Maxwell LK, Roe HA, Morton AJ.To determine (1) the dose of liposomal bupivacaine (LB) to eliminate grade 2 of 5 lameness, the (2) duration of analgesia of LB versus bupivacaine hydrochloride (BH), and (3) LB pharmacokinetics versus BH. Methods: A reversible lameness model was validated in conditioned Thoroughbred horses (n = 12), aged 3 to 10 years. A dose-response trial compared subjective and objective lameness following abaxial sesamoid block with 25 mg BH/nerve or 30, 60, or 133 mg LB/nerve (n = 3/group). The LB dose that eliminated lameness and reduced lameness for the longest was used for blinded, randomized, crossov...
Ebeling-Koning NE, Fowler JT, DelBianco JD, Surmaitis RM.Veterinary medication exposure may result in human toxicity, with approximately 6,000 exposures to veterinary-only medications reported to poison centers in 2022. There is a paucity of literature on the management of poisoned patients secondary to pharmaceuticals intended for equine use. Pergolide is a dopamine and serotonin receptor agonist and is currently approved to treat equine Cushing's disease. It was previously approved in the United States (US) to treat Parkinson's disease in humans; however, it was withdrawn from the market in 2007 due to its association with valvular heart disease....
Wong ASY, Yuen BP, Wong COL, Kong FK, So YM, Kwok WH, Brooks L, Wan TSM, Ho EN.Bisphosphonates and myo-inositol trispyrophosphate (ITPP) are two classes of difficult-to-detect polar drugs that are prohibited under the rules of racing. ITPP is a drug capable of increasing the amount of oxygen in hypoxic tissues, and studies have shown that administration of ITPP increases the maximal exercise capacity in mice. The properties of ITPP make it an ideal candidate as a doping agent to enhance performance in racehorses. In recent years, ITPP had indeed been detected in racehorses and confiscated items. As for bisphosphonates, it is especially critical to control their use as si...
Kilcoyne I, Nieto J, Nottle BF, Flynn H, Knych HK.Addition of morphine to the perfusate while performing intravenous regional limb perfusion (IVRLP) may be helpful in treating painful infectious orthopaedic conditions of the distal limb. Objective: The main objective of this study was to determine synovial morphine concentrations following IVRLP with morphine alone or in combination with amikacin. Methods: Randomised cross-over in vivo experiment. Methods: Six horses underwent IVRLP with 0.1 mg/kg morphine sulphate diluted to 60 mL using 0.9% NaCl (M group) or combined with 2 g amikacin and 0.9% NaCl (MA group) with a 2-week washout per...
Shokrollahi S, Mohammadi R, Sarrafzadeh-Rezaei F, Jalilzadeh-Amin G, Hashemi-Asl SM.The aim of this study was to compare the sedative and cardiovascular effects of the combination of xylazine-acepromazine versus xylazine-pregabalin - in horses. Four healthy crossbred horses were included in the study and assigned to two treatments. In treatment I (T1), the animals received xylazine hydrochloride (1.00 mg kg) in combination with acepromazine maleate (0.05 mg kg) intravenously. In treatment II (T2), the animals received intragastric administration of pregabalin (4.00 mg kg) followed by xylazine hydrochloride (1.00 mg kg) intravenously after 60 min. Head height above ground (HHA...
Hubbell JAE, Muir WW, Gorenberg E, Hopster K.Horses are the most challenging of the common companion animals to anesthetize. Induction of anesthesia in the horse is complicated by the fact that it is accompanied by a transition from a standing position to recumbency. The purpose of this article is to review the literature on induction of anesthesia with a focus on the behavioral and physiologic/pharmacodynamic responses and the actions and interactions of the drugs administered to induce anesthesia in the healthy adult horse with the goal of increasing consistency and predictability.
Ferran AA, Roques BB, Chapuis L, Kuroda T, Lacroix MZ, Toutain PL, Bousquet-Melou A, Lallemand EA.Benzylpenicillin (BP) is a first-line antibiotic in horses but there are discrepancies between manufacturers and literature recommendations regarding dosing regimen. Objectives of this study were to evaluate pharmacokinetics and local tolerance of four different formulations of BP in adult horses, and to suggest optimized dosing regimen according to the formulation. Unassigned: A cross-over design was used in 3 phases for the intramuscular injection of three different products: procaine BP alone, procaine BP/ benzathine BP combination or penethamate hydriodide were administered IM in the glute...
Zscherpe P, Kalbitz J, Weber LA, Paschke R, Mäder K, von Rechenberg B, Cavalleri JV, Meißner J, Klein K.Gray horses are predisposed to equine malignant melanoma (EMM) with advancing age. Depending on the tumor's location and size, they can cause severe problems (e.g., defaecation, urination, feeding). A feasible therapy for EMM has not yet been established and surgical excision can be difficult depending on the location of the melanoma. Thus, an effective and safe therapy is needed. Naturally occurring betulinic acid (BA), a pentacyclic triterpene and its synthetic derivate, NVX-207 (3-acetyl-betulinic acid-2-amino-3-hydroxy-2-hydroxymethyl-propanoate) are known for their cytotoxic properties ag...
Nelson GR, Mama KR, Weiner D, McKemie DS, Kass PH, Steinmetz SJ, Knych HK.This study describes the pharmacokinetics and pharmacodynamics, including antinociceptive effects, of a transdermal buprenorphine solution in horses. It was hypothesized that transdermal application would lead to sustained blood concentrations and antinociceptive effects with fewer adverse effects compared with intravenous (IV) injection. Methods: Prospective nonrandomized four-part parallel experimental study. Methods: A group of eight horses (three mares and five geldings) aged 6-12 years. Methods: Horses were administered incremental doses of 15, 30 and 45 μg kg of buprenorphine transderma...
Emmerich IU.In 2023, no new active pharmaceutical ingredients were released on the German market for horses and food-producing animals. Two established veterinary active pharmaceutical ingredients became available for additional species: The phosphorus compound butafosfan was also approved for horses, dogs, and cats and the mineral sodium chloride as an isotonic sodium chloride solution was also approved for rabbits and guinea pigs. In addition, for small animals, there were new releases of an agent (pergolidmesilate) in a novel pharmaceutical formulation and a lower content of the active ingredient, one ...
Morris J, Hoang D.This article discusses a rare case of isolated xylazine overdose in a human, treated successfully with naloxone. Xylazine, typically used as a veterinary tranquilizer, acts as a potent α2 adrenergic agonist, leading to sedation, muscle relaxation, and potential respiratory depression. In this case, a female mistakenly injected herself with xylazine mistaking it for a different medication. The report discusses naloxone's role beyond opioid overdose, especially regarding substances causing central nervous system (CNS) depression via mechanisms similar to those of opioids. While naloxone is trad...
Reed RA, Berghaus LJ, Reynolds RM, Holmes BT, Krikorian AM, Sakai DM, Ishikawa Y, Knych HK.Understanding the pharmacokinetics and pharmacodynamics of fentanyl in horses is crucial for optimizing pain management strategies in veterinary medicine. Unassigned: Six adult horses were enrolled in a randomized crossover design. Treatments included: placebo, two 100 mcg/h patches (LDF), four 100 mcg/h patches (MDF), and six 100 mcg/h patches (HDF). Patches were in place for 72 h. Blood was obtained for fentanyl plasma concentration determination, thermal threshold, mechanical threshold, heart rate, respiratory rate, and rectal temperature were obtained prior patch placement and at m...
Kuroda T, Minamijima Y, Niwa H, Mita H, Tamura N, Fukuda K, Toutain PL, Ohta M.Fosfomycin (FOM) is an approved veterinary medicinal product for large animals in Japan, but Clinical breakpoint (CBP) for antimicrobial susceptibility test (AST) is not defined for animals. This study aimed at conducting a pharmacokinetics/pharmacodynamics (PK/PD) analysis to determine the PK/PD cutoff for the CBP in horses. Drug concentrations following single intravenous administration (IV) of 20 mg/kg body weight (BW) FOM in nine horses were measured using liquid chromatography/mass spectrometry. The data were modelled using a nonlinear mixed-effects model, followed by Monte Carlo simulati...
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...
Vergara-Hernandez FB, Nielsen BD, Kottwitz JJ, Panek CL, Robison CI, Paris BL, Welsh TH, Bradbery AN, Leatherwood JL, Colbath AC.To determine the single-dose pharmacokinetics of clodronate disodium (CLO) in juvenile sheep and the plasma protein binding (PPB) of CLO in juvenile sheep and horses. Methods: 11 juvenile crossbred sheep (252 ± 6 days) for the pharmacokinetic study. Three juvenile crossbred sheep (281 ± 4 days) and 3 juvenile Quarter Horses (599 ± 25 days) for PPB analysis. Methods: CLO concentrations were determined using liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental analysis from plasma samples obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, and 72 hours ...
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...
McLean AK, Falt T, Abdelfattah EM, Middlebrooks B, Gretler S, Spier S, Turoff D, Navas Gonzalez FJ, Knych HK.Recent approval of transdermal flunixin meglumine (FM) (Banamine®) in cattle has opened the door for the drug's potential application in other species. Transdermal FM could provide a safe and effective form of pain relief in donkeys. In order to evaluate the pharmacokinetics and effects of FM on anti-inflammatory biomarkers in donkeys, a three-way crossover study design was employed. In total, 6 healthy donkeys were administered transdermal (TD) FM at a dosage of 3.3 mg/kg, and oral (PO) and intravenous (IV) doses of 1.1 mg/kg body weight. Blood samples were collected over 96 h to determine t...
Di Cesare F, Negro V, Ravasio G, Villa R, Draghi S, Cagnardi P.Gabapentin is an anticonvulsant drug, which presents an established clinical efficacy in human patients for the management of refractory partial seizures, secondarily generalized tonic-clonic seizures, and for the control of chronic neuropathic pain. Gabapentin was synthesized as a structural analogue of the inhibitory neurotransmitter GABA, with GABA-mimetic effects, able to cross the blood-brain barrier. In veterinary medicine, is extra-label used in combination with other treatments to control seizures when other drugs are no longer effective or become toxic or for neuropathic pain treatmen...
Beaumont RE, Smith EJ, Zhou L, Marr N, Thorpe CT, Guest DJ.We investigated how Interleukin 1 beta (IL-1β) impacts equine tenocyte function and global gene expression in vitro and determined if these effects could be rescued by pharmacologically inhibiting nuclear factor-κB (NF-B) or interleukin 1 signalling. Equine superficial digital flexor tenocytes were cultured in three-dimensional (3D) collagen gels and stimulated with IL-1β for two-weeks, with gel contraction and interleukin 6 (IL6) measured throughout and transcriptomic analysis performed at day 14. The impact of three NF-B inhibitors on gel contraction and IL6 secretion were measured in 3D ...
Bishop RC, Wilkins PA, Kemper AM, Stewart RM, McCoy AM.Nonsteroidal anti-inflammatory drug (NSAID) administration carries risks of gastrointestinal toxicity. Selective COX-2 inhibitors ("coxibs") were designed to reduce risks of adverse effects but are still associated with gastrointestinal complications in humans. The effect of coxibs on colonic inflammation and integrity in horses is unknown. The study objective was to compare the effects of the coxib firocoxib and the nonselective NSAID flunixin meglumine on ultrasonographic indicators of colonic inflammation in healthy horses. Twelve healthy adult horses were administered flunixin meglumine (1...
Mercer MA, Davis JL, McKenzie HC.This review firstly examines the underlying pathophysiology of pain and inflammation associated with orthopedic disease and endotoxemia. Then, it reviews the clinical pharmacology (pharmacokinetics and pharmacodynamics) of both conventional and non-conventional NSAIDs in the adult horse, and finally provides an overview of different modalities to evaluate the therapeutic efficacy of NSAIDs in research.
Auckburally A, Wiklund M, Lord P, Nyman G.To measure changes in regional lung perfusion using CT angiography in mechanically ventilated, anesthetized ponies administered pulsed inhaled nitric oxide (PiNO) during hypotension and normotension. Methods: 6 ponies for anesthetic 1 and 5 ponies for anesthetic 2. Methods: Ponies were anesthetized on 2 separate occasions, mechanically ventilated, and placed in dorsal recumbency within the CT gantry. Pulmonary arterial, right atrial, and facial arterial catheters were placed. During both anesthetics, PiNO was delivered for 60 minutes and then discontinued. Anesthetic 1: hypotension (mean arter...
Owens JG, Kamerling SG, Stanton SR, Keowen ML, Prescott-Mathews JS.To compare the analgesic and anti-inflammatory effects of the nonsteroidal anti-inflammatory drugs (NSAID), ketoprofen (2.20 and 3.63 mg/kg of body weight) and phenylbutazone (4.40 mg/kg), in an acute equine synovitis model. Methods: 4 groups of 6 horses received NSAID or saline solution in a randomized design. Methods: 24 clinically normal mares and geldings. Methods: Left intercarpal joints were injected with sterile carrageenan to induce synovitis at the same time as IV administration of NSAID or saline solution. Clinical assessments were made and synovial fluid was withdrawn at 0, 1, 3, 6,...
Berghaus LJ, Giguère S, Guldbech K.The objectives of this study were to determine the mutant prevention concentration (MPC), time above the MPC and mutant selection window for 10 antimicrobial agents against Rhodococcus equi and to determine if the combination of a macrolide with rifampin would decrease emergence of resistant mutants. Antimicrobial agents investigated (erythromycin, clarithromycin, azithromycin, rifampin, amikacin, gentamicin, enrofloxacin, vancomycin, imipenem, and doxycycline) were selected based on in vitro activity and frequency of use in foals or people infected with R. equi. Each antimicrobial agent or co...
Massoco C, Palermo-Neto J.Benzodiazepines (BDZ) are among the most frequently used class of psychotropic drugs employed in veterinary medicine in Brazil and worldwide due to their anxiolytic, muscle relaxant and anticonvulsant effects [J. Clin. Pharmacol. 33 (1993) 124]. Peripheral benzodiazepine receptor (PBR) sites were described in peripheral organs, endocrine steroidogenic tissues and immune organs and cells. Midazolam is a mixed-type agonist of PBRs. The present study is focused on the effects of midazolam on equine peripheral blood neutrophils, peritoneal macrophages and cortisol levels in plasma. Adult horses we...
Armstrong RA, Lawrence RA, Jones RL, Wilson NH, Collier A.1. This study describes attempts to compare prostacyclin (IP-) receptors in human, pig, horse, rabbit and rat platelets and in circular muscle of human, rabbit and dog mesenteric and pig gastroepiploic arteries. Three stable prostacyclin analogues, iloprost, cicaprost and 6a-carba-prostacyclin (6a-carba-PGI2) and a prostaglandin endoperoxide analogue EP 157 (previously shown to mimic prostacyclin on human platelets) were used. 2. Our main conclusion is that prostacyclin receptors on human, pig and horse platelets are similar in nature, but distinct from those on rabbit and rat platelets. Funct...
Robertson SA, Sanchez LC, Merritt AM, Doherty TJ.Commonly used analgesics (nonsteroidal anti-inflammatory agents, opioids and alpha2-agonists) have unwanted side effects. An effective alternative with minimal adverse effects would benefit clinical equine pain management. Objective: To compare the effect of lidocaine or saline on duodenal and rectal distension threshold pressure and somatic thermal threshold in conscious mature horses. Objective: Systemically administered lidocaine would increase somatic and visceral nociceptive thresholds. Methods: Lidocaine (2 mg/kg bwt bolus followed by 50 microg/kg bwt/min for 2 h) or saline was administe...
Garrison KL, Sahin S, Benet LZ.This study was conducted to determine the number of drugs exhibiting flip-flop pharmacokinetics following oral (p.o.) dosing from immediate-release dosage forms and if they exhibit a common characteristic that may be predicted based on BDDCS classification. The literature was searched for drugs displaying flip-flop kinetics (i.e., absorption half-life larger than elimination half-life) in mammals in PubMed, via internet search engines and reviewing drug pharmacokinetic data. Twenty two drugs were identified as displaying flip-flop kinetics in humans (13 drugs), rat (nine drugs), monkey (three ...
Jamila N, Khairí·ªn M, Yeong KK, Osman H, Murugaiyah V.Context: Garcinia hombroniana Pierre, known as manggis hutan in Malaysia is a rich source of xanthones and benzophenones. Objective: This study was aimed to isolate and characterize potential cholinesterase inhibitors from the extracts of G. hombroniana bark and investigate their interactions with the enzymes. Methods: The dichloromethane extract afforded five triterpenoids which were characterized by NMR and mass spectral techniques. Cholinesterase inhibitory assay and molecular docking were performed to get insight of the inhibitory activity and molecular interactions of the compounds. The c...
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...
Barragry TB.The avermectins were introduced in 1981 and constitute a potent new class of anthelmintic agents. They are naturally-derived products of microbial action displaying an exceptionally wide range of antiparasitic efficacy against internal and external parasites of domestic animals. This paper reviews their isolation and chemistry, mechanism of action, chemical efficacy and safety in cattle, sheep, swine, horses and dogs.
Yocom AF, O'Fallon ES, Gustafson DL, Contino EK.Cannabidiol (CBD) products are widely marketed to horse owners, trainers, and veterinarians and are readily available to the consumer despite minimal pharmacokinetic or safety data being available. The objectives of this study were to determine the plasma pharmacokinetics, short-term safety, and synovial fluid levels of CBD following oral administration in horses. A prospective, randomized, controlled study design was used. Twelve horses were administered sunflower lecithin oil-based CBD at either 1 mg/kg (Group 1) or 3 mg/kg (Group 2) for a 24-hour pharmacokinetic study. Horses then received ...
Campbell WC.The avermectins are macrocyclic lactones produced by Streptomyces avermitilis. One of them has been chemically modified and given the non-proprietary name ivermectin. The compounds have shown efficacy against various stages of filarial parasites. With respect to pre-adult stages in the mammalian host, activity has been observed against Dirofilaria immitis in ferrets and dogs, and Dipetalonema viteae and Litomosoides carinii in jirds (Meriones); but activity has not been observed against the developing stages of Brugia spp. in jirds or Onchocerca spp. in cattle. The compounds have not shown act...
Clode AB, Davis JL, Salmon J, Michau TM, Gilger BC.To determine penetration of topically and orally administered voriconazole into ocular tissues and evaluate concentrations of the drug in blood and signs of toxicosis after topical application in horses. Methods: 11 healthy adult horses. Methods: Each eye in 6 horses was treated with a single concentration (0.5%, 1.0%, or 3.0%) of a topically administered voriconazole solution every 4 hours for 7 doses. Anterior chamber paracentesis was performed and plasma samples were collected after application of the final dose. Voriconazole concentrations in aqueous humor (AH) and plasma were measured via...
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...
Bryant CE, England GC, Clarke KW.The sedative effects in horses of the new alpha 2 agonist medetomidine were compared with those of xylazine. Four ponies and one horse were treated on separate occasions with two doses of medetomidine (5 micrograms/kg bodyweight and 10 micrograms/kg bodyweight) and with one dose of xylazine (1 mg/kg bodyweight) given by intravenous injection. Medetomidine at 10 micrograms/kg was similar to 1 mg/kg xylazine in its sedative effect but produced more severe and more prolonged ataxia, and one animal fell over during the study. Medetomidine at 5 micrograms/kg produced less sedation but a similar deg...
Kvaternick V, Pollmeier M, Fischer J, Hanson PD.The primary objective of this study was to determine the pharmacokinetic profile of firocoxib, a novel second generation coxib, in horses. Horses were administered either a single oral or intravenous dose of firocoxib at 0.1 mg/kg in a two-period crossover study with 12 animals. The dosage was based on previously determined pharmacodynamic parameters. Oral firocoxib was well absorbed with an average bioavailability (absolute) of 79% and a Cmax of 75 ng/mL at 3.9 h. The average elimination half-life was 30 h. Following intravenous administration the average Cmax was 210 ng/mL and the eliminatio...
Derksen FJ, Olszewski MA, Robinson NE, Berney C, Hakala JE, Matson CJ, Ruth DT.To determine the dose of aerosolized albuterol sulfate required to cause bronchodilation in horses with recurrent airway obstruction (RAO) and duration of this effect. Methods: 19 horses with RAO (10 in experiment 1; 9 in experiment 2). Methods: Horses were moved from pasture to stables, and airway obstruction was induced. Pulmonary function was measured in 10 horses before and 5, 10, and 30 minutes after administration of vehicle or 120, 240, 360, or 720 microg of the drug. Nine horses received vehicle or 360 or 720 microg of albuterol, and pulmonary function was measured at baseline and 5 mi...
Haugaard MM, Pehrson S, Carstensen H, Flethøj M, Hesselkilde EZ, Praestegaard KF, Diness JG, Grunnet M, Jespersen T, Buhl R.Only few pharmacologic compounds have been validated for treatment of atrial fibrillation (AF) in horses. Studies investigating the utility and safety of flecainide to treat AF in horses have produced conflicting results, and the antiarrhythmic mechanisms of flecainide are not fully understood. Objective: To study the potential of flecainide to terminate acutely induced AF of short duration (≥ 15 minutes), to examine flecainide-induced changes in AF duration and AF vulnerability, and to investigate the in vivo effects of flecainide on right atrial effective refractory period, AF cycle length...
Di Cesare F, Negro V, Ravasio G, Villa R, Draghi S, Cagnardi P.Gabapentin is an anticonvulsant drug, which presents an established clinical efficacy in human patients for the management of refractory partial seizures, secondarily generalized tonic-clonic seizures, and for the control of chronic neuropathic pain. Gabapentin was synthesized as a structural analogue of the inhibitory neurotransmitter GABA, with GABA-mimetic effects, able to cross the blood-brain barrier. In veterinary medicine, is extra-label used in combination with other treatments to control seizures when other drugs are no longer effective or become toxic or for neuropathic pain treatmen...
Lees P, Toutain PL.The presence of horse meat in food products destined for human consumption and labelled as beef has raised several concerns of public interest. This review deals solely with one aspect of these concerns; samples of equine tissue from horses destined for the human food chain have tested positive for the non-steroidal anti-inflammatory drug, phenylbutazone. The safety of some or all such foods for human consumers is a major concern, because it was shown many years ago that phenylbutazone therapy in humans can be associated with life threatening blood dyscrasias. As an initial basis for assessing...
Bettschart-Wolfensberger R, Clarke KW, Vainio O, Aliabadi F, Demuth D.The pharmacokinetics of intravenous (i.v.) medetomidine (7 mcg kg(-1)) were best described by a two-compartment model in five ponies. Total body clearance was 4 (SD 0.60) 1 kg h,(-1)t(1/2alpha)7. 6 (0.91) minutes and t(1/2beta)51.3 (13.09) minutes. In one pony the one-compartmental model was best fit, and total body clearance was 4. 2 l kg h(-1)and t(1/2)was 11 minutes. Medetomidine plasma levels had fallen below the limits of quantification (0.05 ng ml(-1)) within 4 hours. Medetomidine 5 mcg kg(-1)i.v. followed by an infusion of 3.5 mcg kg h(-1)for two hours provided a constant level of sedat...
Muir WW.N-Methyl-D-aspartate (NMDA) is a synthetic chemical binding molecule (ligand) that selectively binds to the "slow response" glutamate NMDA receptor (NMDAR). NMDARs are important for normal brain function and play a central role in learning, memory, and the development of central nervous system hyperactive states. Diverse chemicals belonging to various drug families have demonstrated NMDAR antagonistic effects. Ketamine has been shown to produce antihyperalgesic effects produced by incision and tissue or nerve damage, and has become popular in equine practice as an anesthetic and more recently ...
Clarke KW, Paton BS.The effects of administration of one of four opiates (pethidine 1 mg/kg bodyweight (bwt), morphine 0.1 mg/kg bwt, methadone 0.1 mg/kg bwt, and butorphanol 0.05 mg/kg bwt) given intravenously to horses and ponies already sedated with detomidine (10 micrograms/kg bwt) were investigated. Behavioural, cardiovascular and respiratory effects of the combinations were compared with those occurring with detomidine alone. Addition of the opiate increased the apparent sedation and decreased the response of the animal to external stimuli. At doses used, butorphanol produced the most reliable response. Sid...
Terry RL, McDonnell SM, Van Eps AW, Soma LR, Liu Y, Uboh CE, Moate PJ, Driessen B.Gabapentin is being used in horses although its pharmacokinetic (PK) profile, pharmacodynamic (PD) effects and safety in the equine are not fully investigated. Therefore, we characterized PKs and cardiovascular and behavioral effects of gabapentin in horses. Gabapentin (20 mg/kg) was administered i.v. or p.o. to six horses using a randomized crossover design. Plasma gabapentin concentrations were measured in samples collected 0-48 h postadministration employing liquid chromatography-tandem mass spectrometry. Blood pressures, ECG, and sedation scores were recorded before and for 12 h after gaba...
Sykes BW, Kathawala K, Song Y, Garg S, Page SW, Underwood C, Mills PC.Pilot investigations have suggested that a novel, long-acting, injectable i.m. formulation of omeprazole (LA-OMEP) can induce acid suppression for up to 7 days following a single injection. Objective: To investigate the pharmacodynamics and assess the clinical efficacy of the LA-OMEP formulation. Methods: Part A comprised a pharmacodynamic study. Part B consisted of a pilot clinical trial. Methods: Part A enrolled six adult Thoroughbred horses with percutaneous gastrotomy tubes. Intragastric pH was measured for continuous 23-h periods (08.00-07.00 h) for eight consecutive days (days 0-7). A si...
Naylor RJ, Taylor AH, Knowles EJ, Wilford S, Linnenkohl W, Mair TS, Johns IC.Ex vivo evidence suggests that cyclo-oxygenase (COX) 2-preferential inhibitor nonsteroidal anti-inflammatory drugs (NSAIDs), such as meloxicam, have a less detrimental effect on intestinal healing than flunixin meglumine (FM). Whether this translates to a beneficial effect in horses with naturally occurring strangulating small intestinal (SSI) lesions is unknown. Objective: To compare the clinical outcome of horses with naturally occurring SSI lesions treated with meloxicam or FM. Methods: Randomised prospective study. Methods: Cases presenting to the Royal Veterinary College Equine Referral H...
Rezende ML, Grimsrud KN, Stanley SD, Steffey EP, Mama KR.The aim of the study was to describe the pharmacokinetics and selected pharmacodynamics of intravenous dexmedetomidine in horses. Eight adult horses received 5 μg/kg dexmedetomidine IV. Blood samples were collected before and for 10 h after drug administration to determine dexmedetomidine plasma concentrations. Pharmacokinetic parameters were calculated using noncompartmental analysis. Data from one outlier were excluded from the statistical summary. Behavioral and physiological responses were recorded before and for 6 h after dexmedetomidine administration. Dexmedetomidine concentrations dec...
Martinez M, Modric S.In veterinary medicine, the characterization of a drug's pharmacokinetic (PK) properties is generally based upon data that are derived from studies that employ small groups of young healthy animals, often of a single breed. These are also the data from which population predictions are often generated to forecast drug exposure characteristics in the target population under clinical conditions of use. In veterinary medicine, it is rare to find information on the covariates that can influence drug exposure characteristics. Therefore, it is important to recognize some of the factors that can alter...
Dillon PF, Root-Bernstein R, Robinson NE, Abraham WM, Berney C.Previous in vitro research demonstrated that ascorbate enhances potency and duration of activity of agonists binding to alpha 1 adrenergic and histamine receptors. Objective: Extending this work to beta 2 adrenergic systems in vitro and in vivo. Methods: Ultraviolet spectroscopy was used to study ascorbate binding to adrenergic receptor preparations and peptides. Force transduction studies on acetylcholine-contracted trachealis preparations from pigs and guinea pigs measured the effect of ascorbate on relaxation due to submaximal doses of beta adrenergic agonists. The effect of inhaled albuter...
Hamamoto-Hardman BD, Steffey EP, Weiner D, McKemie DS, Kass P, Knych HK.The objective of the current study was to describe and characterize the pharmacokinetics and selected pharmacodynamic effects of morphine and its two major metabolites in horses following several doses of morphine. A total of ten horses were administered a single intravenous dose of morphine: 0.05, 0.1, 0.2, or 0.5 mg/kg, or saline control. Blood samples were collected up to 72 hr, analyzed for morphine, and metabolites by LC/MS/MS, and pharmacokinetic parameters were determined. Step count, heart rate and rhythm, gastrointestinal borborygmi, fecal output, packed cell volume, and total prote...
