Pharmacokinetics in horses involves the study of how drugs are absorbed, distributed, metabolized, and excreted in equine species. This field of study provides insights into the time course of drug concentrations within the horse's body and helps in understanding the effects of various pharmaceuticals. Key parameters in equine pharmacokinetics include absorption rates, bioavailability, half-life, and clearance. These parameters can vary significantly due to factors such as age, breed, and health status of the horse. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacokinetic profiles of different drugs in horses, aiming to optimize dosing regimens and improve therapeutic outcomes in equine medicine.
Gokbulut C, McKellar QA.Internal parasites of horses comprise an intractable problem conferring disease, production and performance losses. Parasitism can rarely be controlled in grazing horses by management alone and anthelmintic drugs have formed the basis of therapy and prophylaxis for the last sixty years. The pharmacology of the anthelmintic drugs available dictate their spectrum of activity and degree of efficacy, their optimal routes of administration and characteristics which prevent some routes of administration, their safety tolerance and potential toxicities and as a consequence of their persistence in the...
Wang J, Xue J, Kong J, Li J, Zhang S, Cao X.The pharmacokinetic properties of vitacoxib have not been established completely; current dosage recommendations are based on clinical experiences. The primary objective of this study was to describe plasma concentrations and characterize the pharmacokinetics of vitacoxib formulation following oral administrations in horses. Also, the effect of the state of stomach contents on the absorption of vitacoxib was investigated in fed/fasted horses. Blood samples were collected prior to and at various times up to 72 hr post-administration. Drug concentrations were measured using ultra high-performan...
Fontenot RL, Langston VC, Zimmerman JA, Wills RW, Sloan PB, Mochal-King CA.To determine meropenem concentrations in radiocarpal (RC) joint fluid and plasma after intravenous regional limb perfusion (IVRLP). Methods: In vivo experimental study. Methods: Nine healthy adult mares. Methods: Meropenem (500 mg) was injected in the forelimb of standing sedated horses via IVRLP with a pneumatic tourniquet inflated to 400 mmHg. Synovial fluid was collected from RC joints at 0, 0.5, 1, 2, 4, 6, 8, 12, and 18 hours after meropenem injection. Blood samples were collected from the jugular vein at the same time points and at 5 and 15 minutes following injection. Meropenem concentr...
Soma LR, You Y, Robinson MA, Boston RC.Intravenous (iv), subcutaneous (sq), and topical (tp) lidocaine was administered to six horses in a cross-over, randomized design study. Samples were collected for up to 72 hr. Compartmental models were used to investigate the pharmacokinetics of (LD) and its metabolites 3-hydroxylidocaine (3-OH), 4-hydroxylidocaine (4-OH), and monoethylglycinexylidide (MEGX). Metabolites 3-OH and 4-OH were present in conjugated forms, whereas LD and metabolite MEXG were present primarily in the un-conjugated form. Plasma concentrations of LD after iv administration (100 mg) were described by three-compartme...
Stein F, Gilliam L, Davis J, Taylor J.In a randomized crossover design study, 10 adult horses were administered crushed metronidazole tablets rectally at 20 mg/kg. Horses' rectums were either evacuated (E) or not evacuated (NE) of manure prior to the administration of the drug. Serum samples were taken over 24 hr and plasma concentrations were determined via high pressure liquid chromatography. At 15 min post-administration, group E had a significantly higher plasma concentration (p = 0.027), but there were no concentration differences at any other time points. There was large variability in relative bioavailability in the NE...
Knych HK, McKemie DS, Seminoff K, Hartmann P, Hovda L, Benson D.Ethylphenidate is a psychostimulant and analog of the commonly prescribed compound, methylphenidate (Ritalin®). There are a limited number of studies describing the disposition and pharmacologic/toxicological effects of ethylphenidate in any species. The abuse potential in equine athletes along with the limited data available regarding administration in horses necessitates further study. The objectives of the current study were to describe drug concentrations, develop an analytical method that could be used to regulate its use, and describe the pharmacodynamic effects of ethylphenidate in hor...
Zak A, Siwinska N, Slowikowska M, Borowicz H, Szpot P, Zawadzki M, Niedzwiedz A.Capsaicin and dihydrocapsaicin are alkaloids with analgesic effects in humans and animals. When used locally, both of them minimalise pain sensation by defunctionalising nerve endings. According to the Federation Equestrian International Prohibited Substances List, these are substance banned in horse competitions. The aim of the study was to determine the detection time of capsaicin in both plasma and serum after long-term use of a gel recommended for commercial use and applied as intended. The objective of the study was to select the best material for the detection of capsaicin as a doping su...
Watson Levings RS, Broome TA, Smith AD, Rice BL, Gibbs EP, Myara DA, Hyddmark EV, Nasri E, Zarezadeh A, Levings PP, Lu Y, White ME, Dacanay EA....Toward the treatment of osteoarthritis (OA), the authors have been investigating self-complementary adeno-associated virus (scAAV) for intra-articular delivery of therapeutic gene products. As OA frequently affects weight-bearing joints, pharmacokinetic studies of scAAV gene delivery were performed in the joints of the equine forelimb to identify parameters relevant to clinical translation in humans. Using interleukin-1 receptor antagonist (IL-1Ra) as a secreted therapeutic reporter, scAAV vector plasmids containing codon-optimized cDNA for equine IL-1Ra (eqIL-1Ra) were generated, which produc...
Roska S, Morello S, Rajamanickam V, Smith LJ.Effects of lactated Ringer's solution (LRS) and hetastarch 130/0.4 (HES) on colloid osmotic pressure (COP), plasma osmolality (OSM) and total protein (TP) were investigated in 18 inhalational-anaesthetised healthy horses. Horses received 4-6 ml/kg LRS (LRS; n=9) or HES (HES; n=9) from anaesthesia induction through 60 min, after which all were administered LRS. COP, TP and OSM were measured before premedication (baseline), postinduction and 30 (n=18), 60 (n=18), 90 (n=18) and 120 (n=12) minutes. Baseline COP, OSM and TP were not different between groups. TP decreased in both groups at all t...
Sandker MJ, Duque LF, Redout EM, Klijnstra EC, Steendam R, Kops N, Waarsing JH, van Weeren R, Hennink WE, Weinans H.The aim of this study was to develop a formulation with a sustained intra-articular release of the anti-inflammatory drug tacrolimus. Drug release kinetics from the prepared tacrolimus loaded monodisperse biodegradable microspheres based on poly(d-l-lactide-PEG)--poly(l-lactide) multiblock copolymers were tunable by changing polymer composition, particularly hydrophobic-hydrophilic block ratio. The monospheres were 30 μm and released the drug, depending on the formulation, in 7 to >42 days. The formulation exhibiting sustained release for 1 month was selected for further in vivo evaluation...
Vissani MA, Zabal O, Tordoya MS, Parreño V, Thiry E, Barrandeguy M.Equid alphaherpesvirus 3 (EHV3) is the etiological agent of equine coital exanthema (ECE), which is a venereal, highly contagious disease, characterized by the formation of papules, vesicles, pustules and ulcers on the external genitalia of mares and stallions. EHV3 remains in a latent state after a successful infection and there are latently infected animals in which the virus is reactivated and generally re-excreted subclinically. There are no available vaccines for this condition and prevention is based on the clinical examination of mares prior to mating, which allows to segregate those sh...
Agne GF, Jung SW, Wooldridge AA, Duran SH, Ravis W, Toribio R.Diuretic treatment is the mainstay for management of congestive heart failure in horses, and its use has been restricted to injectable medications because no currently data supports the use of PO administered loop diuretics. Objective: To determine the pharmacokinetic and pharmacodynamic properties of PO administered torsemide and, determine if PO administered torsemide, could be used as an alternative to injectable diuretics in the horse. Methods: Six healthy adult mares. Methods: A 2-phase, prospective study, that consisted of pharmacokinetic profiling of a single dose (6 mg/kg PO) and pharm...
Mason LV, Moroney JR, Mason RJ.Guidelines regarding the impact and value of prophylaxis or maintenance therapy in equine gastric ulcer syndrome (EGUS) are not well-established or defined. The merits and the magnitude of effects of prophylaxis for spontaneous or recurrent squamous gastric ulceration in horses in training are uncertain. Objective: To pool data from randomised controlled trials (RCTs) to eliminate reporting bias and evaluate the efficacy of prophylactic omeprazole in the prevention of EGUS in training horses, and secondarily to compare prophylactic dosages of omeprazole. Methods: Meta-analysis. Methods: This m...
Pakkanen SAE, de Vries A, Raekallio MR, Mykkänen AK, Palviainen MJ, Sankari SM, Vainio OM.Romifidine, an α-2 adrenoceptor agonist, is a widely-used sedative in equine medicine. Besides the desired sedative and analgesic actions, α-2 adrenoceptor agonists have side effects like alterations of plasma concentrations of glucose and certain stress-related hormones and metabolites in various species. Vatinoxan (previously known as MK-467), in turn, is an antagonist of α-2 adrenoceptors. Because vatinoxan does not cross the blood brain barrier in significant amounts, it has only minor effect on sedation induced by α-2 adrenoceptor agonists. Previously, vatinoxan is shown to prevent th...
Emmerich IU.In 2017, no new active pharmaceutical ingredients were released on the German market for horses or food-producing animals. Four established veterinary active pharmaceutical ingredients became available for additional species: the ectoparasitic Fluralaner (Exzolt®) of the isoxazoline group was additionally authorized for chickens, the macrolide antibiotics Gamithromycin (Zactran®) and Tulathromycin (Draxxin®) for sheep and the nonsteroidal anti-inflammatory drug Tolfenamic Acid (Tolfedol®) from the fenamate group for cattle and pigs. Additionally, one drug with a new combination of active i...
Cokelaere SM, Plomp SGM, de Boef E, de Leeuw M, Bool S, van de Lest CHA, van Weeren PR, Korthagen NM.Synovial inflammation is an important characteristic of arthritic disorders like osteoarthritis and rheumatoid arthritis. Orally administered non-steroidal anti-inflammatory drugs (NSAIDs) such as celecoxib are among the most widely prescribed drugs to manage these debilitating diseases. Intra-articular delivery in biodegradable in situ forming hydrogels overcomes adverse systemic effects and prolongs drug retention in the joint. In this study two formulations of celecoxib (40 mg/g and 120 mg/g) in a propyl-capped PCLA-PEG-PCLA triblock copolymer were sequentially evaluated in a multiple L...
Hardefeldt LY, Gilkerson JR, Billman-Jacobe H, Stevenson MA, Thursky K, Browning GF, Bailey KE.Antimicrobial resistance is a public health emergency, placing veterinary antimicrobial use under growing scrutiny. Antimicrobial stewardship, through appropriate use of antimicrobials, is a response to this threat. The need for antimicrobial stewardship in Australian veterinary practices has had limited investigation. A 2016 survey undertaken to investigate antimicrobial usage patterns by Australian veterinarians found that antimicrobial dose rates were varied and often inappropriate. Doses of procaine penicillin in horses and cattle were often low, with 68% and 90% of respondents, respective...
Sandbaumhüter FA, Thormann W.Glucuronidation catalyzed by uridine-5'-diphospho-glucuronosyl-transferases (UGTs) is the most important reaction in phase II metabolism of drugs and other compounds. O-glucuronidation is more common than N-glucuronidation. The anesthetic, analgesic and antidepressive drug ketamine is metabolized in phase I by cytochrome P450 enzymes to norketamine, hydroxynorketamine (HNK) diastereomers and dehydronorketamine (DHNK). Equine urine samples collected two hours after ketamine injection were treated with β-glucuronidase and analyzed with three enantioselective capillary electrophoresis assays. Co...
Sandbaumhüter FA, Vimercati S, Thormann W, Mevissen M.The anesthetic ketamine is often combined with analgesics and benzodiazepines in equine medicine. Therefore, drug-drug interactions are possible. Enzyme kinetics for ketamine N-demethylation were determined using equine CYP3A94, CYP3A95 and CYP3A97, and the effect of medetomidine, diazepam and methadone on the ketamine metabolism was studied in vitro. Ketamine was incubated with the CYPs or equine liver microsomes (ELM) alone or in presence of medetomidine, diazepam and/or methadone for different times. Norketamine levels were determined using enantioselective capillary electrophoresis (CE) wi...
Bergstrom TC, Sakai RR, Nieto JE.A mare was euthanized because of gastric rupture secondary to complete duodenal obstruction by 2 bezoars located in the pylorus and proximal duodenum. Infrared spectroscopy showed that the bezoars were composed of psyllium. The mare had been receiving treatment with a pelleted psyllium product at 4 times the recommended dosage. Veterinarians should be aware that treatment of colic in horses with pelleted psyllium products could be associated with gastric impaction. Rupture gastrique catastrophique secondaire à des pharmacobézoards de psyllium en boulettes chez un cheval. Une jument a été e...
Tapio HA, Raekallio MR, Mykkänen A, Mama K, Mendez-Angulo JL, Hautajärvi H, Vainio OM.OBJECTIVE To compare the effects of MK-467 and hyoscine butylbromide on detomidine hydrochloride-induced cardiorespiratory and gastrointestinal changes in horses. ANIMALS 6 healthy adult horses. PROCEDURES Horses received detomidine hydrochloride (20 μg/kg, IV), followed 10 minutes later by MK-467 hydrochloride (150 μg/kg; DET-MK), hyoscine butylbromide (0.2 mg/kg; DET-HYO), or saline (0.9% NaCl) solution (DET-S), IV, in a Latin square design. Heart rate, respiratory rate, rectal temperature, arterial and venous blood pressures, and cardiac output were measured; blood gases and arterial plas...
The ultra long-acting β -adrenoceptor agonist olodaterol plus the ultra long-acting muscarinic antagonist tiotropium bromide are known to relax equine airways. In human bronchi combining these drugs elicits a positive interaction, thus we aimed to characterize this information further in equine isolated airways stimulated by electrical field stimulation (EFS) and using the Concentration-Reduction Index (CRI) and Combination Index (CI) equations. The drugs were administered alone and together by reproducing ex vivo the concentration-ratio delivered by the currently available fixed-dose combina...
Durham AE.Therapeutic drug monitoring and minimum inhibitory concentration (MIC) data allow more informed use of gentamicin. Objective: To measure peak and trough serum gentamicin concentrations in horses after a 6.6 mg/kg dose of gentamicin given IV and the MIC of gentamicin of bacteria for which gentamicin might be selected. Methods: Retrospective analysis of hospital records. Peak and trough plasma gentamicin concentrations were measured after 6.6 mg/kg gentamicin IV in 339 hospitalized horses. The MIC of gentamicin was measured for 503 isolates from ambulatory practice and 33 from hospital practice....
Knych HK, Seminoff K, McKemie DS.Traditional therapeutic options for the treatment of lameness associated with inflammation in performance horses include administration of cyclooxygenase enzyme inhibiting non-steroidal anti-inflammatory drugs (NSAID). As long-term use of these drugs can adversely impact the health of the horse, anti-inflammatories with a more favorable safety profile are warranted. Grapiprant is a newly approved non-cyclooxygenase inhibiting NSAID that has demonstrated efficacy and safety in other species and which may be a valuable alternative to traditional NSAIDs used in the horse. The objectives of the cu...
Kim Y, Seo C, Oh S, Kwak J, Jung S, Sin E, Kim H, Ji M, Lee HS, Park HJ, Lee G, Yu J, Kim M, Lee W, Paik MJ.Loxoprofen is a non-steroidal anti-inflammatory drug of the 2-arylpropionic acid type, which has used to treat musculoskeletal disorders in the horse racing industry. However, it has also used illicitly to mask clinical signs of inflammation and pain in racehorses. Thus, its accurate analysis has become an important issue in horse doping laboratories. In this study, an analytical method of loxoprofen was developed as tert-butyldimethylsilyl (TBDMS) derivative by gas chromatography-mass spectrometry (GC-MS). Characteristic fragment ions of [M-15], [M-57], and [M-139] permitted the accurate and ...
Liu Y, Siard M, Adams A, Keowen ML, Miller TK, Garza F, Andrews FM, Seeram NP.The human health benefits attributed to turmeric/curcumin spice has resulted in its wide utilization as a dietary supplement for companion pets and other animals including horses. While the quantification of free curcuminoids (curcumin, demethoxycurcumin, bisdemethoxycurcumin) and their phase-2 metabolites (curcumin-O-sulfate, curcumin-O-glucuronide) have been extensively investigated in human and rodent biological samples (primarily plasma and serum), there is lack of similar data for horses. Herein, we report a validated LC-ESI-MS/MS method for the simultaneous quantification of the aforemen...
Viljanto M, Hillyer L, Hincks P, Pearce C, Paine SW.Medication control and doping control have been established in horse racing to ensure the integrity of the sport and the welfare of the horses. This ensures that horses do not compete under the influence of any drugs, including omeprazole, a therapeutic medication used to treat equine gastric ulcer syndrome. In this study, pharmacokinetic data were produced in equine plasma and urine following an oral administration of 4 mg/kg of generic buffered formulation of omeprazole to six Thoroughbred horses in five daily doses to determine an appropriate screening limit and detection time in equine pl...
Kilcoyne I, Nieto JE, Knych HK, Dechant JE.OBJECTIVE To determine the maximum concentration (Cmax) of amikacin and time to Cmax (Tmax) in the distal interphalangeal (DIP) joint in horses after IV regional limb perfusion (IVRLP) by use of the cephalic vein. ANIMALS 9 adult horses. PROCEDURES Horses were sedated and restrained in a standing position and then subjected to IVRLP (2 g of amikacin sulfate diluted to 60 mL with saline [0.9% NaCl] solution) by use of the cephalic vein. A pneumatic tourniquet was placed 10 cm proximal to the accessory carpal bone. Perfusate was instilled with a peristaltic pump over a 3-minute period. Synovial ...
Choi TLS, Wong JKY, Kwok WH, Curl P, Mechie S, Wan TSM.Methylstenbolone (2,17α-dimethyl-5α-androst-1-en-17β-ol-3-one) is a synthetic anabolic and androgenic steroid (AAS) sold as an oral 'nutritional supplement' under the brand names 'Ultradrol', 'M-Sten' and 'Methyl-Sten'. Like other AASs, methylstenbolone is a prohibited substance in both human and equine sports. This paper describes the studies of the in vitro and in vivo metabolism of methylstenbolone in horses using LC/HRMS, GC/MS and GC/MS/MS. Phase I in vitro metabolic study of methylstenbolone was performed using homogenised horse liver. Hydroxylation was the only biotransformation obse...
Daglish J, Mama KR.This article provides a brief overview of pain physiology and its relevance to equine patients. Objective and subjective techniques for assessing pain in the horse are described in depth. Pharmacologic and interventional pain modulation treatments are discussed with a focus on the rehabilitating horse.
Burrows GE.Endotoxins are non-protein fragments of the cell wall of Gram-negative bacteria. They must be absorbed into the circulation to produce disease and systemic effects are similar, regardless of bacterial source. Absorption of endotoxins occurs in obstructive bowel disease and may play a significant part in determining the severity of the disease. Many of the responses to experimentally administered endotoxin are identical to those of bowel diseases or the horse and include circulatory, haematological and metabolic alterations. Therapeutic approaches are indirect and include many drugs currently e...
Weber LA, Puff C, Kalbitz J, Kietzmann M, Feige K, Bosse K, Rohn K, Cavalleri JV.The naturally occurring betulinic acid (BA) and its derivative NVX-207 show anticancer effects against equine malignant melanoma (EMM) cells and a potent permeation in isolated equine skin in vitro. The aim of the study was to determine the in vivo concentration profiles of BA and NVX-207 in equine skin and assess the compounds' local and systemic tolerability with the intent of developing a topical therapy against EMM. Eight horses were treated percutaneously in a crossover design with 1% BA, 1% NVX-207 or a placebo in a respective vehicle twice a day for seven consecutive days with a seven-d...
Wiederkehr A, Barbarossa A, Ringer SK, Jörger FB, Bryner M, Bettschart-Wolfensberger R. To assess drug plasma levels, preanesthetic sedation, cardiopulmonary effects during anesthesia and recovery in horses anesthetized with isoflurane combined with medetomidine or xylazine. Prospective blinded randomized clinical study. Sixty horses undergoing elective surgery. Thirty minutes after administration of antibiotics, flunixine meglumine or phenylbutazone and acepromazine horses received medetomidine 7 μg kg (group MED) or xylazine 1.1 mg kg (group XYL) slowly intravenously (IV) and sedation was assessed 3 min later. Anesthesia was induced with ketamine/diazepam and maintained wi...
Aida H, Mizuno Y, Hobo S, Yoshida K, Fujinaga T.The minimum alveolar concentration (MAC) of sevoflurane required to prevent gross purposeful movement in response to electrical stimulation of the oral mucous membranes was determined in horses, and their physical responses to inhalation of this anesthetic were observed. The MAC was 2.31 +/- 0.11%. The horses showed good ventilation, without any signs of airway irritation such as coughing. The horses became slightly excited before they laid down. The end tidal sevoflurane concentration (ESC) required to produce recumbency was 2.54 +/- 0.11%. These results suggest that sevoflurane is a clinical...
Villalba M, Santiago I, Gomez de Segura IA.Lidocaine and ketamine are administered to horses as a constant rate infusion (CRI) during inhalation anaesthesia to reduce anaesthetic requirements. Morphine decreases the minimum alveolar concentration (MAC) in some domestic animals; when administered as a CRI in horses, morphine does not promote haemodynamic and ventilatory changes and exerts a positive effect on recovery. Isoflurane-sparing effect of lidocaine, ketamine and morphine coadministration has been evaluated in small animals but not in horses. Objective: To determine the reduction in isoflurane MAC produced by a CRI of lidocaine ...
Villarino N, Martín-Jiménez T.Macrolides are used for treatment of pneumonia and extrapulmonary conditions caused by Rhodococcus equi. In foals, macrolides have an extraordinary capacity to accumulate in different lung tissue compartments. These drugs show unique pharmacokinetic features such as rapid and extensive distribution and long persistence in pulmonary epithelial lining fluid (PELF) and bronchoalveolar lavage (BAL) cells from foals. This article reviews the pharmacokinetic characteristics of erythromycin, azithromycin, clarithromycin, tulathromycin, telithromycin, gamithromycin, and tilmicosin in foals, with empha...
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...
Lyons ET, Tolliver SC, Drudge JH, Granstrom DE, Collins SS, Stamper S.The activity of moxidectin was evaluated in 1988 and 1989 against natural infections of internal parasites in 20 critical tests (n = 20 equids) and three controlled tests (n = 20 equids). Two formulations, injectable administered intramuscularly (i.m.) or intraorally (i.o.) and gel i.o., were given at dose rates of 0.2, 0.3 or 0.4 mg kg-1 body weight. For the critical tests (all three dose rates evaluated), removals of second instar Gasterophilus intestinalis were 93-100%, except (89%) for the injectable formulation (i.m.) at 0.2 mg kg-1. Removals of third instar G. intestinalis were 88-100% f...
Brosnan RJ.Inhaled agents represent an important and useful class of drugs for equine anesthesia. This article reviews the ether-type anesthetics in contemporary use, their uptake and elimination, their mechanisms of action, and their desirable and undesirable effects in horses.
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...
Crabtree NE, Epstein KL.Despite the frequent inclusion of fluid therapy in the treatment of many conditions in horses, there are limited studies available to provide evidenced-based, species-specific recommendations. Thus, equine fluid therapy is based on the application of physiology and extrapolation from evidence in other veterinary species and human medicine. The physiologic principles that underly the use of fluids in medicine are, at first glance, straightforward and simple to understand. However, in the past 20 years, multiple studies in human medicine have shown that creating recommendations based on theory i...
Back W, MacAllister CG, van Heel MC, Pollmeier M, Hanson PD.Lameness is a highly prevalent condition in horses and the principal cause of removal from athletic activity. In clinical studies to evaluate nonsteroidal anti-inflammatory drug therapies, force plates are commonly used to assess improvement of lameness objectively. Objective: To use a force plate to determine the optimal dose of a new COX-2 inhibitor (firocoxib) that will reduce lameness, when administered orally to horses once daily. Methods: Sixty-four horses that exhibited chronic lameness presumed due to osteoarthritis, including navicular disease, in at least one of the frontlimbs and at...
Salonen JS, Vähä-Vahe T, Vainio O, Vakkuri O.The pharmacokinetics of detomidine, a novel analgesic sedative, was studied in the major target species after high (80 micrograms/kg) i.v. and i.m. doses. In addition, drug residues in some organs were determined. Concentrations were measured using a sensitive, detomidine-specific radio-immunoassay method. Rapid absorption following i.m. dosing occurred. Absorption half-lives were 0.15 h (horse) and 0.08 h (cattle). The mean peak concentration in the horse (51.3 ng/ml) was achieved in 0.5 h and in the cow (65.8 ng/ml) in 0.26 h. The areas under the concentration curve after i.m. dosing were 66...
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...
Hendrix DV, Stuffle JL, Cox SK.To evaluate the pharmacokinetics of topically applied ciprofloxacin 0.3% ophthalmic solution in tears of healthy horses. Methods: Twenty healthy, adult, mixed-breed horses. Methods: Twenty study horses were confirmed free of ophthalmic disease by complete ophthalmic examination. Seventy microliters of 0.3% ciprofloxacin (Ciloxan) was placed in the ventral cul-de-sac of each eye using a microliter syringe and 19-g cannula. Population kinetics were carried out by sampling the tear film from the lower cul-de-sac of each eye with tear test strips at 5, 10, 15 and 30 min and 1, 2, 4 and 6 h post ad...
Alkabes SB, Adams SB, Moore GE, Alkabes KC.To determine whether joint lavage performed simultaneously with IV regional limb perfusion (IVRLP) reduces the effectiveness of IVRLP and to compare 2 types of tourniquets used for this procedure in horses. Methods: 11 adult horses. Methods: 2 groups of 6 horses were tested by use of a pneumatic or an Esmarch tourniquet (1 horse was tested twice [once in each group]). Standing IVRLP with amikacin (500 mg) was performed for 30 minutes. Simultaneously, the metacarpophalangeal joint was lavaged with 2 L of lactated Ringer's solution and the egress fluids were collected. Samples of the distal inte...
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...
Wohlfender FD, Doherr MG, Driessen B, Hartnack S, Johnston GM, Bettschart-Wolfensberger R.Multicentre Confidential Enquiries into Perioperative Equine Fatalities (CEPEF) have not been conducted since the initial CEPEF Phases 1-3, 20 years ago. Objective: To collect data on current practice in equine anaesthesia and to recruit participants for CEPEF-4. Methods: Online questionnaire survey. Methods: An online questionnaire was prepared and the link distributed internationally to veterinarians possibly performing equine anaesthesia, using emails, posters, flyers and an editorial. The questionnaire included 52 closed, semiclosed and open questions divided into 8 subgroups: demographic ...
Ballard S, Shults T, Kownacki AA, Blake JW, Tobin T.After intravenous (i.v.) injection, acepromazine was distributed widely in the horse (Vd = 6.6 litres/kg) and bound extensively (greater than 99%) plasma proteins. Plasma levels of drug declined with an alpha half-life of 4.2 min, while the beta phase or elimination half-life was 184.8 min. At a dosage level of 0.3 mg/kg acepromazine was detectable in the plasma for 8 h post dosing. The whole blood partitioning of acepromazine was 46% in the plasma phase and 54% in the erythrocyte phase. Penile prolapse was clearly evident at doses from 0.01 mg/kg to 0.4 mg/kg i.v., and the duration and extent...
Soma LR, Uboh CE, Guan F, McDonnell S, Pack J.Anabolic steroids (ABS) boldenone (BL; 1.1 mg/kg) and stanozolol (ST; 0.55 mg/kg) were administered i.m. to horses and the plasma samples collected up to 64 days. Anabolic steroids and androgenic steroids (ANS) in plasma were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The limit of detection of all analytes was 25 pg/mL. The median absorption (t1/2 partial differential) and elimination (t1/2e) half-lives for BL were 8.5 h and 123.0 h, respectively, and the area under the plasma concentration-time curve (AUCho) was 274.8 ng.h/mL. The median t1/2e for ST was 82.1 ...
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...
Dirikolu L, Lehner F, Nattrass C, Bentz BG, Woods WE, Carter WG, Karpiesiuk W, Jacobs J, Boyles J, Harkins JD, Granstrom DE, Tobin T.Diclazuril (4-chlorophenyl [2,6-dichloro-4-(4,5-dihydro-3H-3,5-dioxo-1,2,4-triazin-2-yl)pheny l] acetonitrile), is a benzeneacetonitrile antiprotozoal agent (Janssen Research Compound R 64433) marketed as Clinacox . Diclazuril may have clinical application in the treatment of Equine Protozoal Myeloencephalitis (EPM). To evaluate its bioavailability and preliminary pharmacokinetics in the horse we developed a sensitive quantitative high-pressure liquid chromatography (HPLC) method for diclazuril in equine biological fluids. MS/MS analysis of diclazuril in our HPLC solvent yielded mass spectral ...
Divers TJ, Irby NL, Mohammed HO, Schwark WS.Information on antibiotic concentrations in the equine eye following systemic therapy is limited. Reports that Leptospira spp. are frequently present in the eyes of horses with recurrent uveitis, emphasises a need for studies on ocular concentrations of specific antibiotics. Objective: 1) Enrofloxacin, administered i.v. at 7.5 mg/kg bwt q. 24 h, results in aqueous humour concentrations greater than the reported minimum inhibitory concentration (MIC) for Leptospira pomona. 2) Aqueous humour paracentesis sufficiently disrupts the blood-aqueous humour barrier (BAB) to cause an increase in aqueous...
De Clercq D, van Loon G, Tavernier R, Verbesselt R, Deprez P.To investigate effects of IV administration of propafenone for naturally occurring and experimentally induced chronic atrial fibrillation in horses. Methods: 2 horses with naturally occurring atrial fibrillation and 4 horses with pacing-induced atrial fibrillation. Methods: Horses received a bolus of propafenone (2 mg/kg, IV over 15 minutes). If atrial fibrillation persisted after 20 minutes, a continuous infusion of propafenone (7 microg/kg/min) was given for 120 minutes. Before, during, and after treatment, plasma propafenone concentrations, hematologic and serum biochemical values, and elec...
Devine EP, KuKanich B, Beard WL.To determine the pharmacokinetics of morphine after IM administration in a clinical population of horses. Methods: Prospective clinical study. Methods: 77 horses. Methods: Morphine sulfate (0.1 mg/kg [0.045 mg/lb], IM) was administered to horses, and blood samples were obtained at predetermined time points. Plasma morphine concentrations were measured via liquid chromatography and mass spectrometry. In preliminary investigations, samples were obtained from 2 healthy horses at 12 time points (up to 12 hours after drug administration) and analyzed via 2-stage pharmacokinetic analysis. In the cli...
