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.
Minuto J, Bedenice D, Ceresia M, Zaghloul I, Böhlke M, Mazan MR.Nebulized lidocaine appears promising as a novel corticosteroid-sparing therapeutic for equine asthma, but its safety and pharmacokinetic behavior have yet to be confirmed. Unassigned: To describe the effect of nebulized lidocaine on upper airway sensitivity, lung mechanics, and lower respiratory cellular response of healthy horses, as well as delivery of lidocaine to lower airways, and its subsequent absorption, clearance, and duration of detectability. Unassigned: Six healthy university- and client-owned horses with normal physical examination and serum amyloid A, and no history of respirato...
Ishii H, Shibuya M, Leung GN, Yamashita S, Nagata SI, Kushiro A, Sakai S, Toju K, Okada J, Kawasaki K, Kusano K, Kijima-Suda I.For the purpose of doping control, this is the first report of accurate quantification of four critical structural isomers of nicotine metabolites (trans-3'-hydroxycotinine, cis-3'-hydroxycotinine, 5'-hydroxycotinine, and N'-hydroxymethylnorcotinine) in equine plasma and urine for the establishment of their elimination profiles. Besides, the pharmacokinetic studies of trans-3'-hydroxycotinine and N'-hydroxymethylnorcotinine in equine plasma and urine are also presented for the first time. Methods: The accurate quantification methods of the aforementioned four structural isomers in horse plasma...
Ekstrand C, Michanek P, Gehring R, Sundell A, Källse A, Hedeland M, Ström L.Atropine is an essential part of the treatment protocol for equine uveitis. Topical atropine administration has been associated with decreased intestinal motility and abdominal pain in horses. Experimental studies have indicated that frequent dosing is associated with a higher risk than dosing every 6 h. Unfortunately, no quantitative pharmacodynamic data for inhibition of the equine gut are published. Unassigned: Eight standardbred horses were assigned to receive either atropine or saline (control) to be infused over 30 min in a two-treatment cross-over design. Atropine concentrations in plas...
Kellon EM, Gustafson KM.Hyperinsulinemia associated with pituitary pars intermedia dysfunction (PPID) and/or equine metabolic syndrome is well documented to put horses at high risk of laminitis. While dietary control of simple sugars and starch is the most effective therapy to control hyperinsulinemia, some horses fail to respond. Ten horses with hyperinsulinemia refractory to diet control, metformin, levothyroxine, and pergolide (if diagnosed with PPID) were treated with sodium-glucose cotransporter-2 inhibitor canagliflozin (Invokana®). Nine horses were hyperglycemic (>5.5 mmol/l) or had a history of hyperglyce...
Burroughs DL, Lorch G, Guo Y, Hill K, Schroeder EL, Cole LK, Phelps MA.Mycophenolate mofetil (MMF) is the prodrug of mycophenolic acid (MPA) which acts as an immunosuppressive agent. During the biotransformation of MMF to MPA, additional metabolites including MPA phenol glucuronide (MPAG), MPA acyl glucuronide (AcMPAG) and MPA phenol glucoside (MPG) are formed. Objective: To define the noncompartmental pharmacokinetic (PK) parameters of three single doses of intravenous (i.v.) MMF and its downstream metabolites in healthy horses. Methods: Six healthy Standardbred mares. Methods: Generic MMF (Par Pharmaceuticals; Chestnut Ridge, NY, USA) was reconstituted and admi...
Knych HK, Kanarr K, Fang Y, McKemie DS, Kass PH.To describe the pharmacokinetics, behavioral and physiologic effects and effects on thermal thresholds of morphine, morphine 6-glucuronide (M6G) and morphine 3-glucuronide (M3G) following administration to horses. Methods: Randomized balanced crossover study. Methods: A total of seven University-owned horses, five mares and two geldings, aged 3-6 years. Methods: Horses were treated with a single intravenous dosage of saline, morphine (0.2 mg kg), M6G (0.01 mg kg) and M3G (0.03 mg kg). Blood was collected prior to (baseline) and at several times post administration. Drug and metabolite concentr...
Amorim GB, Segabinazzi LG, Oliveira OM, Perecmanis S, Arruda R, Canisso IF.Misoprostol, a synthetic PGE1, is becoming a common therapy for mares with suspected uterine tube obstruction. Recently, there have been concerns that uterine administration of misoprostol induces exacerbated uterine inflammation; however, this has not been critically evaluated. This study aimed to assess the inflammatory response and potential systemic reactions after uterine administration of misoprostol, either during prebreeding or immediately after postembryo flushing. Privately owned embryo donor mares (n = 11) were randomly assigned in a crossover design to receive misoprostol (3 mL +...
Werners A, Karasek I, Butler C, Yeatts J, Enomoto H, Baynes R.Several different tick species are known to infest horses. Aside from causing serious health and welfare issues, including anaemia, ill thrift, and immunosuppression, ticks can transmit a variety of important, sometimes zoonotic, pathogens. The successful prevention and treatment of tick infestations have been described, but the information is scarce and, in many instances, anecdotal. Here we describe a practical and affordable prevention of tick infestation by using abamectin-impregnated cattle ear tags affixed to a safety collar. We have assessed the radial distribution of abamectin by analy...
Reed R, Trenholme N, Skrzypczak H, Chang K, Ishikawa Y, Barletta M, Quandt J, Knych H, Sakai D.To compare the effects of hydromorphone and butorphanol in horses undergoing arthroscopy and describe the pharmacokinetics of hydromorphone in anesthetized horses. Methods: Randomized controlled clinical trial. Methods: A total of 40 adult horses admitted for elective arthroscopy. Methods: Horses were randomly assigned to be administered intravenous hydromorphone (0.04 mg kg-1; group TxH; n = 19) or butorphanol (0.02 mg kg-1; group TxB; n = 21) prior to surgery as part of a standardized anesthetic protocol. Pain was scored by two observers unaware of group assignment using the Equine Utrecht...
Hoffmann SL, Seminoff K, McKemie DS, Kass PH, Knych HK.Grapiprant is a prostaglandin E2 receptor antagonist that has been found to be an effective anti-inflammatory in dogs and that is devoid of some of the adverse effects associated with traditional NSAIDs that elicit their effects through inhibition of PGE2 production. Previously published reports have described the pharmacokinetics of this drug in horses when administered at 2 mg/kg; however, pharmacodynamic effects in this species have yet to be described. The objective of the current study was to describe the pharmacokinetics and pharmacodynamics of grapiprant at a higher dose. Eight horses...
Kondampati KD, Saini SPS, Sidhu PK, Anand A, Kumar D, Beesam S, Bedi JS, Kaur R, Bhardwaj R.The pharmacokinetics of ampicillin-cloxacillin, given as single intravenously dose of 10 mg.kg-1 (5 mg.kg-1 of ampicillin plus 5 mg.kg-1 of cloxacillin) was examined in clinically presented Indian thoroughbred horses (n = 6) in order to design appropriate dosing strategies. Drug concentrations in plasma were determined by high performance liquid chromatography (HPLC) and pharmacokinetic parameters were derived by non-compartmental analysis using WinNonlin software. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of ampicillin-cloxacillin against qualit...
Haughan JE, Missanelli JR, You Y, Stefanovski D, Soma LR, Robinson MA.Glaucine, an aporphine alkaloid with anti-tussive, anti-inflammatory, and anti-nociceptive properties, has been identified in post-race samples from racehorses. To investigate pharmacokinetics of glaucine in horses, a three-way crossover study of intravenous and oral glaucine (0.1 mg/kg) and orally administered tulip poplar shavings (50 g shavings = 0.001 mg/kg glaucine) was performed in six horses. A two-compartment model best described IV administration with alpha ( ) and beta ( ) half-life lives of 0.3 (0.1-0.7) and 3.1 (2.4-7.8) h, respectively. The area under the curve ( ) was ...
Mahalingam-Dhingra A, Mazan MR, Bedenice D, Ceresia M, Minuto J, Deveney EF.There are limited options for treatment of the common disease, equine asthma. The aim of this study was to estimate the feasibility and potential efficacy of using nebulized lidocaine for treating equine asthma, while at the same time treating a separate cohort of asthmatic horses with inhaled budesonide. Nineteen horses with a history consistent with equine asthma were recruited from our referral population for a double-blind, randomized, controlled pilot clinical trial using Consolidated Standards of Reporting Trials (CONSORT) guidelines. After screening, 16 horses met the inclusion criteria...
Gustafsson K, Tatz AJ, Britzi M, Dahan R, Sutton GA, Kelmer G.Eight horses underwent IVRLP at two occasions through a 23-gauge 2Â cm long butterfly catheter. Regional anaesthesia of the ulnar, median and medial cutaneous antebrachial nerves was performed prior, and an 8Â cm rubber tourniquet was placed on the proximal radius for 30Â minutes following the infusion. The first infusion consisted of 2Â g of amikacin sulphate and 10Â mg of dexamethasone phosphate diluted with 0.9% NaCl to a total volume of 100Â ml. The second perfusion was performed after a 2-week washout period, the same protocol was used but without dexamethasone phosphate. Synovial fluid s...
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 ...
Jurek KA, Schoonover MJ, Williams MR, Rudra P.To determine the influence of perfusate volume on synovial fluid amikacin concentrations in the joints of the hind limb after standing saphenous intravenous regional limb perfusion (IVRLP). Methods: Randomized crossover design. Methods: Six adult horses. Methods: Saphenous IVRLP was performed in 6 standing horses with 1 g of amikacin diluted with 0.9% NaCl to volumes of 10 ml, 60 ml, and 120 ml. Samples of synovial fluid from the tarsocrural, metatarsophalangeal, and hind limb distal interphalangeal joints were collected at 15 and 30 min after perfusate administration. Concentrations ...
Ekstrand C, Nostell K, Gehring R, Bondesson U, Bröjer J.Septicaemia in the neonatal foal is caused by both Gram positive and Gram negative bacteria. The life-threatening nature of this condition requires treatment to be initiated with broad spectrum antimicrobial drugs pending antimicrobial susceptibility testing. Potentiated sulphonamides, for example, trimethoprim combined with sulfadiazine, could be clinically relevant options but their pharmacokinetics in the neonatal foal are unknown. To describe the plasma disposition of trimethoprim and sulfadiazine in neonatal foals and to relate the results to patterns in the minimum inhibitory concentrati...
Gold JR, Grubb TL, Cox S, Malavasi L, Villarino NL.The repeated administration of high doses of gabapentin may provide better analgesia in horses than current clinical protocols. Objective: Administration of gabapentin at 40 and 120 mg/kg PO q 12 h for 14 days will not alter serum biochemistry findings or cause adverse effects. Our objectives were to evaluate the effect of gabapentin on serum biochemistry, physical examination, and plasma pharmacokinetics of gabapentin. Methods: Six healthy adult mares. Methods: Horses received 40 and 120 mg/kg of gabapentin orally q 12 h for 14 days. Horses were examined and scored for ataxia and ...
Bergstrom TC, Kilcoyne I, Magdesian KG, Nieto JE.To determine whether IV regional limb perfusion (IVRLP) performed in the cephalic vein with a wide rubber tourniquet (WRT) applied proximal and distal to the carpus results in a higher peak concentration (Cmax) of amikacin in the radiocarpal joint (RCJ), compared with the Cmax for IVRLP using a single WRT proximal to the carpus. Methods: 7 healthy adult horses. Methods: Horses underwent IVRLP using standing sedation with 2 g of amikacin sulfate diluted to 60 mL by use of saline (0.9% NaCl) solution in the cephalic vein with 2 different tourniquet techniques; proximal WRT (P) and proximal and d...
Hunyadi L, Datta P, Rewers-Felkins K, Sundman E, Hale T, Fajt V, Wagner S.The objective of this study was to determine the pharmacokinetic parameters of oclacitinib maleate as a top dress given to adult horses. Six adult horses with a mean weight of 528Â kg were administered a single dose of 0.5Â mg/kg oclacitinib maleate. Blood was collected prior to drug administration and at 15Â min, 30Â min, 45Â min, 1, 2, 4, 6, 8, 12, 24, 48, and 72Â h after treatment. Oclacitinib maleate plasma concentrations were measured by liquid chromatography/mass spectrometry. Pharmacokinetic parameters were found best to fit a one-compartment model. Mean C was 486Â ng/ml (range 423-549Â...
Rizk MA, El-Sayed SAE, Eltaysh R, Igarashi I.Equine piroplasmosis is a tick-transmitted disease that is considered one of the most serious infectious diseases affecting equines. Searching for novel antipiroplasm drugs remains indispensable due to the emergence and spreading of resistant piroplasm parasites against the limited currently used drugs, diminazene aceturate and imidocarb dipropionate. Therefore, novel drugs with specified targets need to be identified and exploited. The inhibitory effects of Medicines for Malaria Venture (MMV) Malaria Box compounds with potent in vitro anti-equine piroplasmosis activity were evaluated against ...
Schellenberg LM, Regenthal R, Abraham G.This research paper investigates the influence of the Rho kinase (ROCK) inhibitor Y-27632 on β2-adrenoceptor density and the generation of a cellular messenger called cAMP in horse bronchial cells. The [...]
Luethy D, Robinson MA, Stefanovski D, Haughan J, Torcivia C, Kowalski A, Ford M, You Y, Missanelli J, Slack J.Cardiac drugs with defined pharmacological parameters in horses are limited. The objective of this study was to characterize the pharmacokinetic properties and cardiovascular effects of intravenous and oral metoprolol tartrate (MET) in horses. In a 2-period randomized cross-over design, MET was administered IV (0.04Â mg/kg) and PO (6Â mg/kg) once to six healthy adult horses. Horses were monitored via continuous telemetry and non-invasive blood pressure (NIBP). Blood samples were serially collected for 72Â h post-administration, and concentrations were determined by LC-MS/MS. Pharmacokinetics w...
Nichols CL, Doherty TJ, Schumacher J, Jones PD, Sun X.To determine whether palmar digital nerve (PDN) blockade in horses with a combination of dexmedetomidine and mepivacaine would block the response to mechanical force applied to the digit longer than would anesthetizing these nerves with mepivacaine alone or dexmedetomidine alone. Methods: 8 mares with no signs of lameness. Methods: In a randomized, crossover, blinded, experimental study, both PDNs of the same forelimb of each horse were anesthetized by perineural injection with either 30 mg mepivacaine alone, 250 µg of dexmedetomidine alone, or 30 mg mepivacaine combined with 250 µg of dexme...
Kuroda T, Minamijima Y, Nomura M, Yamashita S, Yamada M, Nagata S, Mita H, Tamura N, Fukuda K, Kuwano A, Kusano K, Toutain PL, Sato F.For medication control in several jurisdictions, withdrawal time is the period of refrain from racing after drug administration. It is set by adding a safety period to an experimental detection time. However, there are no reports of statistical analyses of detection time for the determination of withdrawal time in flunixin meglumine-treated horses. Objective: To analyse the population pharmacokinetics of flunixin in horses through the generation of a dataset for detection time statistical analysis and predictions via Monte Carlo simulation. Methods: Experimental study. Methods: Drug plasma and...
Loomes K, Louro LF.The recovery phase after equine general anaesthesia (GA) is a time of considerable risk and therefore has been the subject of extensive research over the last 20Â years. Various pharmacological interventions have been developed and studied with the objective of improving recovery quality and reducing anaesthetic-related mortality and morbidity. Nevertheless, some controversy remains regarding the influence of anaesthetic protocol choice on recovery quality from GA and its implications for recovery-related mortality and morbidity. A systematic review of the literature investigating the influenc...
Waitt Wolker LH, Veltri CA, Pearman K, Lozoya M, Norris JW.This study aimed to investigate pharmacokinetics of fluoxetine in horses and validate a method for liquid chromatography mass spectrometry analysis of serum levels. Fluoxetine pharmacokinetics were determined using 10Â healthy, adult horses. Fluoxetine pharmacokinetics following a single oral dose (0.25Â mg/kg) were determined using blood samples collected prior to and at several time points over 7Â days following administration. Serum concentrations of fluoxetine and its bioactive metabolite norfluoxetine were measured using liquid chromatography coupled to an accurate mass/high-resolution ma...
Bishop RC, Kemper AM, Wilkins PA, McCoy AM.Equine gastric ulcer syndrome (EGUS) is a common and significant cause of morbidity in horses, with a range of clinical signs, including inappetence, colic and poor performance. Hospitalised horses are exposed to factors that may induce EGUS, including fasting and nonsteroidal anti-inflammatory drug (NSAID) administration, and may be at risk for development of squamous (ESGD) and glandular gastric disease (EGGD). Prophylactic anti-ulcer medication is often prescribed for these patients, but drug selection is complicated by different aetiology and response to treatment of ESGD and EGGD. Objecti...
Barton AK, Gehlen H.The term remodeling describes the process resulting in a tissue that is structurally and architecturally altered compared to its healthy counterpart. At least in severe equine asthma, this occurs mainly, but not exclusively, as a consequence of neutrophilic airway inflammation and is characterized by hypertrophy of the smooth muscle layers in airway and arterial walls as well as fibrosis of the bronchial walls and pulmonary interstitial tissue. To date, much less is known for mild to moderate equine asthma. For a long time it was assumed that these processes are irreversible, and at least for ...
McReynolds CB, Yang J, Guedes A, Morisseau C, Garcia R, Knych H, Tearney C, Hamamoto B, Hwang SH, Wagner K, Hammock BD.There are few novel therapeutic options available for companion animals, and medications rely heavily on repurposed drugs developed for other species. Considering the diversity of species and breeds in companion animal medicine, comprehensive PK exposures in the companion animal patient is often lacking. The purpose of this paper was to assess the pharmacokinetics after oral and intravenous dosing in domesticated animal species (dogs, cats, and horses) of a novel soluble epoxide hydrolase inhibitor, EC1728, being developed for the treatment of pain in animals. Results: Intravenous and oral adm...
Tobin T, Chay S, Kamerling S, Woods WE, Weckman TJ, Blake JW, Lees P.Phenylbutazone is an acidic, lipophilic, non-steroidal anti-inflammatory drug (NSAID). It is extensively metabolized in the horse. The metabolites so far identified, oxyphenbutazone, gamma-hydroxyoxyphenbutazone, account for some 25-30% of administered dose over 24 h. The plasma half-life of phenylbutazone and termination of its pharmacological action are determined primarily by its rate of hepatic metabolism. Phenylbutazone acts by inhibiting the cyclooxygenase enzyme system, which is responsible for synthesis of prostanoids such as PGE2. It appears to act on prostaglandin-H synthase and pros...
Valverde A.Balanced anesthetic techniques are commonly used in equine patients, and include the combination of a volatile anesthetic with at least one injectable anesthetic throughout the maintenance period. Injectable anesthetics used in balanced anesthesia include the α2-agonists, lidocaine, ketamine, and opioids, and those with muscle-relaxant properties such as benzodiazepines and guaifenesin. Administration of these injectable anesthetics is best using constant-rate infusions based on the pharmacokinetics of the drug, which allows steady-state concentrations and predictable pharmacodynamic actions....
Gustafsson A, BÃ¥verud V, Franklin A, Gunnarsson A, Ogren G, Ingvast-Larsson C.Six healthy adult horses were given repeated administrations of trimethoprim/ sulfadiazine (TMP/SDZ) intravenously (i.v.) (2.5 mg/kg TMP and 12.5 mg/kg SDZ) and orally (p.o.) as a paste (5 mg/kg TMP and 25 mg/kg SDZ). Both formulations were given twice daily for 5 days, with a 3-week interval between i.v. and oral administration. The influence of the drug combination on the intestinal microflora was examined and the plasma concentrations, pharmacokinetic parameters and plasma protein binding were determined. There were no major changes in the bacterial intestinal flora and no clinical evidence...
Saps M, Miranda A.There is little evidence for most of the medications currently used to treat functional abdominal pain disorders (FAPDs) in children. Not only are there very few clinical trials, but also most have significant variability in the methods used and outcomes measured. Thus, the decision on the most appropriate pharmacological treatment is frequently based on adult studies or empirical data. In children, peppermint oil, trimebutine, and drotaverine have shown significant benefit compared with placebo, each of them in a single randomized clinical trial. A small study found that cyproheptadine was be...
Berry DB, Sullins KE.To determine whether povidone iodine ointment or 2 forms of silver sulfadiazine applied topically to wounds of the distal aspect of the limbs in horses affect the rate of second intention healing and to evaluate the additional influence of bandaging with these antimicrobials on granulation tissue formation. Methods: 6 healthy adult horses. Methods: Six standardized 2.5-cm2 skin wounds/horse were distributed between the dorsomedial surfaces of the metacarpi and metatarsi. One of the following 6 treatments was applied to each wound: 1% silver sulfadiazine cream with bandage, 1% silver sulfadiazi...
Lees P, Landoni MF.Carprofen is a nonsteroidal anti-inflammatory drug of the 2-arylpropionate subclass. It contains a single chiral centre and exists in two enantiomeric forms. In this study rac-carprofen, at two dosages, 0.7 and 4.0 mg/kg, and placebo were administered i.v. to six New Forest horses in a three period cross-over study. The concentration-time profiles were established for R(-) and S(+)-carprofen for plasma and both inflamed (exudate) and noninflamed (transudate) tissue cage fluids. R(-)-carprofen was the predominant enantiomer in all three fluids, as indicated by plasma area under the curve (AUC) ...
Muir WW, Sams RA, Huffman RH, Noonan JS.The cardiopulmonary, behavioral, and pharmacokinetic properties of diazepam were determined in horses. Heart rate, cardiac output, mean pulmonary artery, aortic and right atrial blood pressures, respiratory rate, and arterial pH and blood gas values did not change after IV diazepam (0.05, 0.1, 0.2, 0.4 mg/kg) administration. Increasing doses of diazepam resulted in signs of muscle weakness including fixed stance, muscle fasciculations of the head, neck, and thorax muscles, ataxia, and then recumbency. Dosages of diazepam exceeding 0.2 mg/kg produced mild sedation. Behavioral changes persisted ...
Cox S, Villarino N, Sommardahl C, Kvaternick V, Zarabadipour C, Siger L, Yarbrough J, Amicucci A, Reed K, Breeding D, Doherty T.The objective of this study was to determine if a single loading dose (LD), 3× the label dose of firocoxib oral paste, followed by nine maintenance doses at the current label dose achieves and maintains near steady state concentrations. Six healthy, adult mares were administered 0.3mg/kg of firocoxib on Day 0, and 0.1 mg/kg 24 h later on Day 1, and at 24 h intervals from Day 2 to Day 9, for a total of 10 doses. Blood samples were collected throughout the study. The mean firocoxib maximum plasma concentration and standard deviation was 199±97 ng/mL, 175±44 ng/mL and 183±50 ng/mL after the L...
Butt TD, Bailey JV, Dowling PM, Fretz PB.The purpose of this study was to compare the synovial fluid concentrations and pharmacokinetics of amikacin in the equine limb distal to the carpus following intraosseous and intravenous regional perfusion. The front limbs of 6 horses were randomly assigned to either intraosseous or intravenous perfusion. A tourniquet was placed distal to each carpus and the limb perfused with 500 mg of amikacin. Systemic blood samples and synovial fluid samples were collected over 70 min from the distal interphalangeal (DIP) joint, metacarpophalangeal joint, and digital flexor sheath. The tourniquet was remov...
Kaka JS, Klavano PA, Hayton WL.Ketamine HCl was administered IV to xylazine HCl-treated horses. The plasma concentration of ketamine was measured several times after administration of the drug and these data were used to develop a two-compartment pharmacokinetic model. The distribution and the elimination phase half-lives averaged 2.9 and 42 minutes. The volume of the central compartment averaged 212 ml/kg of body weight and the volume of the peripheral compartment was approximately threefold larger. The total body clearance of ketamine averaged 26.6 ml/minute/kg. Plasma protein binding of ketamine averaged 50% over the con...
Mama KR, Grimsrud K, Snell T, Stanley S.Detomidine hydrochloride is used to provide sedation, muscle relaxation and analgesia in horses, but a lack of information pertaining to plasma concentration has limited the ability to correlate drug concentration with effect. Objective: To build on previous information and assess detomidine for i.v. and i.m. use in horses by simultaneously assessing plasma drug concentrations, physiological parameters and behavioural characteristics. Objective: Systemic effects would be seen following i.m. and i.v. detomidine administration and these effects would be positively correlated with plasma drug con...
Hesselkilde EZ, Carstensen H, Haugaard MM, Carlson J, Pehrson S, Jespersen T, Buhl R, Platonov PG.Atrial fibrillatory cycle length has been considered one of the indices of atrial electrical remodelling during atrial fibrillation (AF), which can be assessed from surface ECG by computer-assisted calculation of atrial fibrillatory rate (AFR). Horses have been suggested as a bona fide model for AF studies since horses too, develop lone AF, however data on AF characteristics in horses are extremely sparse and non-invasive characterization of AF complexity using surface ECG processing has not been reported. Objective: The aim was to study characteristics of induced AF and its modification by fl...
Mendoza FJ, Perez-Ecija A, Toribio RE.Donkeys and mules show several pharmacodynamic and pharmacokinetic idiosyncrasies that have to be fully considered by any clinician dealing with these species. Because they possess an increased metabolic rate and cellular water content compared with horses, higher doses (or shorter dosing intervals) are usually recommended for those drugs where pharmacologic studies have been performed. Nonetheless, owing to the lack of species-specific information, this assumption cannot be arbitrarily applied. Thus, when a drug protocol published for horses is extrapolated to a donkey or a mule, a close moni...
Muir WW, Robertson JT.The visceral analgesic, cardiorespiratory, and behavioral effects induced by xylazine, butorphanol, meperidine, and pentazocine were determined in 9 adult horses with colic. Colic was produced by inflating a balloon in the horses' cecum. Heart rate, respiratory rate, mean arterial blood pressure, and cardiac output increased after cecal balloon inflation. Xylazine and butorphanol decreased the hemodynamic response to cecal balloon inflation. Meperidine and pentazocine had minimal effects on the cardiorespiratory changes induced by cecal balloon inflation. Xylazine produced the most pronounced ...
Queiroz-Neto A, Zamur G, Gonçalves SC, Carregaro AB, Mataqueiro MI, Harkins JD, Tobin T.Amitraz, an acaricide used to control ectoparasites in animals has a complex pharmacological activity, including alpha2-adrenergic agonist action. The purpose of this research was to investigate the possible antinociceptive and/or sedative effect of amitraz in horses. The sedative effect of the intravenous (i.v.) injection of dimethylformamide (DMF, 5 mL, control) or amitraz (0.05, 0.10, 0.15 mg/kg), was investigated on the head ptosis test. The participation of alpha2-adrenergic receptors in the sedative effect provoked by amitraz was studied by dosing yohimbine (0.12 mg/kg, i.v.). To measure...
Morris DD, Fregin GF.Seventy-seven horses with atrial fibrillation (AF) were treated orally with quinidine sulfate (QS) at the University of Pennsylvania, School of Veterinary Medicine, Thirty-seven horses (48%) had adverse reactions to QS, the most common of which were nasal mucosal edema, anorexia, colic, and diarrhea. The mean highest daily QS dose was slightly greater in horses showing toxicity (P less than 0.1) and their conversion rate was less (P less than 0.05). A schedule of gradually increasing QS dose was time consuming, costly and not associated with fewer adverse reactions. Horses were compared by the...
Knobloch M, Portier CJ, Levionnois OL, Theurillat R, Thormann W, Spadavecchia C, Mevissen M.Ketamine is widely used as an anesthetic in a variety of drug combinations in human and veterinary medicine. Recently, it gained new interest for use in long-term pain therapy administered in sub-anesthetic doses in humans and animals. The purpose of this study was to develop a physiologically based pharmacokinetic (PBPk) model for ketamine in ponies and to investigate the effect of low-dose ketamine infusion on the amplitude and the duration of the nociceptive withdrawal reflex (NWR). A target-controlled infusion (TCI) of ketamine with a target plasma level of 1 microg/ml S-ketamine over 120 ...
Waterman AE, Robertson SA, Lane JG.The metabolism and distribution of ketamine and its two major metabolites (norketamine and dehydronorketamine) was investigated in 10 horses undergoing airway surgery. Following premedication with xylazine (1.1 mg kg-1 intravenously) anaesthesia was induced by the rapid injection of ketamine at a dose of 2.2 mg kg-1 intravenously. Anaesthesia was maintained with halothane vaporized in oxygen and nitrous oxide (50:50). Serially collected blood samples were analysed by a sensitive gas liquid chromatographic technique. Plasma ketamine concentrations declined biexponentially with a rapid initial d...
Oswald S, Peters J, Venner M, Siegmund W.Clarithromycin (CLA) is a well established macrolide antibiotic which is frequently used in therapy of airway diseases in foals. It is extensively metabolized by CYP3A4 resulting in the antimicrobial active metabolite 14-hydroxyclarithromycin (OH-CLA). Rifampicin (RIF) is often comedicated to prevent resistance and augment therapy. RIF is a known inducer for metabolizing enzymes and transporter proteins. Therefore, comedication might bare the risks of pharmacokinetic drug interactions which were investigated in a clinical trial. As no adequate method to determine CLA, RIF and their main metabo...
Letendre LT, Tessman RK, McClure SR, Kvaternick VJ, Fischer JB, Hanson PD.To determine pharmacokinetic parameters and variables, firocoxib concentrations in urine and plasma, urine-to-plasma ratios, and the urine depletion profile of firocoxib and to evaluate whether the pharmacokinetic behavior of firocoxib was governed by linear processes after multiple doses of firocoxib were administered IV and orally. Methods: 6 healthy female horses (5 Paint horses and 1 Quarter Horse) in experiment 1 and 12 healthy male and female horses in experiment 2. Methods: In experiment 1, 6 horses were orally administered firocoxib paste once daily for 12 consecutive days, and plasma ...
Varley G, Bowen IM, Habershon-Butcher JL, Nicholls V, Hallowell GD.Previous studies have demonstrated a poor response to healing of gastric glandular lesions with oral omeprazole and other medications. Objective: To evaluate the efficacy of two novel treatments (misoprostol [M] and combined omeprazole-sucralfate [OS]) in horses for gastric glandular disease. Methods: Prospective, clinical study. Methods: Sixty-three sports horses with grade >1/4 glandular disease were identified by gastroscopy. Horses received either 5 μg/kg of misoprostol per os BID 1 h prior to feeding or a combination of 4 mg/kg enteric coated omeprazole per os SID and 12 mg/kg suc...
Rush BR, Raub ES, Thomsen MM, Davis EG, Matson CJ, Hakala JE.To evaluate clinical response, pulmonary function, and adrenal gland response to incremental doses of beclomethasone dipropionate in horses with recurrent airway obstruction. Methods: Crossover trial. Methods: 8 horses with recurrent airway obstruction. Methods: Horses randomly assigned to 4 groups were treated twice daily via aerosol administration of placebo or 500, 1,000, or 1,500 micrograms of beclomethasone dipropionate in a crossover design with a 10-day minimum washout period. Subjective assessment of airway obstruction, serum cortisol concentration, and maximum change in pleural pressu...
Driessen B, Nann L, Benton R, Boston R.To study whether hemodynamic function in horses, particularly mean arterial blood pressure (MAP), is better maintained with sevoflurane than isoflurane, thus requiring less pharmacological support. Methods: Prospective randomized clinical investigation. Animals Thirty-nine racehorses undergoing arthroscopy in lateral recumbency. Methods: Horses were assigned to receive either isoflurane (n = 20) or sevoflurane (n = 19) at 0.9-1.0 minimum alveolar concentration (MAC) for maintenance of anesthesia. Besides routine clinical monitoring, cardiac output (CO) was measured by lithium dilution. Hemodyn...
Leclere M, Lefebvre-Lavoie J, Beauchamp G, Lavoie JP.Orally administered prednisolone and dexamethasone are used commonly in the treatment of recurrent airway obstruction (RAO) in horses. However, the efficacy of prednisolone in improving pulmonary function during continuous antigen exposure has not been evaluated critically and there is little evidence supporting the efficacy of low-dose oral dexamethasone in the same conditions. Objective: Oral prednisolone and dexamethasone improve pulmonary function in RAO under conditions of continuous antigen exposure, and dexamethasone is more effective than prednisolone at commonly used dosages. Methods:...
Shilo Y, Britzi M, Eytan B, Lifschitz T, Soback S, Steinman A.Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat moderate to moderately severe pain in humans. The present study investigated tramadol administration in horses by intravenous, intramuscular, oral as immediate-release and oral as sustained-release dosage-form routes. Seven horses were used in a four-way crossover study design in which racemic tramadol was administered at 2 mg/kg by each route of administration. Altogether, 23 blood samples were collected between 0 and 2880 min. The concentration of tramadol and its M1 metabolite were ...
Martinuk SD, Manning AW, Black WD, Murphy BD.The sialylation of eCG was examined to determine its influence on the in vivo metabolism and biological activity of the molecule. Sialic acid was decrementally removed from eCG by incubation with agarose-linked neuraminidase for varying time periods. Pharmacokinetic parameters for the disappearance of 4,000 IU (267 micrograms) of three desialylated eCG preparations (20%, 53%, and 80% sialic acid removed) and control eCG were determined in sheep. The clearance rate of eCG increased (p less than 0.05) with each decrement of sialic acid. The removal of 53% sialic acid enhanced the distribution of...
Lankveld DP, Driessen B, Soma LR, Moate PJ, Rudy J, Uboh CE, van Dijk P, Hellebrekers LJ.Ketamine (KET) possesses analgesic and anti-inflammatory activity at sub-anesthetic doses, suggesting a benefit of long-term KET treatment in horses suffering from pain, inflammatory tissue injury and/or endotoxemia. However, data describing the pharmacodynamic effects and safety of constant rate infusion (CRI) of KET and its pharmacokinetic profile in nonpremedicated horses are missing. Therefore, we administered to six healthy horses a CRI of 1.5 mg/kg/h KET over 320 min following initial drug loading. Cardiopulmonary parameters, arterial blood gases, glucose, lactate, cortisol, insulin, non...
Ringer SK, Portier K, Torgerson PR, Castagno R, Bettschart-Wolfensberger R.To compare xylazine and romifidine constant rate infusion (CRI) protocols regarding degree of sedation, and effects on postural instability (PI), ataxia during motion (A) and reaction to different stimuli. Methods: Blinded randomized experimental cross-over study. Methods: Ten adult horses. Methods: Degree of sedation was assessed by head height above ground (HHAG). Effects on PI, A and reaction to visual, tactile and acoustic stimulation were assessed by numerical rating scale (NRS) and by visual analogue scale (VAS). After baseline measurements, horses were sedated by intravenous loading dos...
Marntell S, Nyman G, Funkquist P, Hedenstierna G.To study pulmonary gas exchange and cardiovascular responses to sedation achieved with romifidine and butorphanol (RB) alone, or combined with acepromazine, and during subsequent tiletamine-zolazepam anaesthesia in horses. Methods: Six (four males and two females) healthy Standardbred trotters aged 3-12 years; mass 423-520 kg. Methods: Randomized, cross-over, experimental study. Methods: Horses were anaesthetized on two occasions (with a minimum interval of 1 week) with intravenous (IV) tiletamine-zolazepam (Z; 1.4 mg kg(-1)) after pre-anaesthetic medication with IV romifidine (R; 0.1 mg kg(-1...
Chou CC, Vickroy TW.To determine the presence of adenosine receptor subtypes A1 and A2a in equine forebrain tissues and to characterize the interactions of caffeine and its metabolites with adenosine receptors in the CNS of horses. Methods: Brain tissue specimens obtained during necropsy from 5 adult male research horses. Methods: Membrane-enriched homogenates from cerebral cortex and striatum were evaluated by radioligand binding assays with the A1-selective ligand [3H]DPCPX and the A2a-selective ligand [3H]ZM241385. Functional responses to adenosine receptor agonists and antagonists were determined by a nucleot...
