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.
Hunyadi L, Papich MG, Pusterla N.The purpose of this study was to determine if a low dose of diclazuril (0.5mg/kg of 1.56% diclazuril pellets) given to six healthy adult horses every 3-4 days for a total of five administrations would achieve steady-state plasma concentrations known to be inhibitory to Sarcocystis neurona and Neospora caninum. Blood was collected via venipuncture immediately before (trough concentrations) and 10h after (peak concentrations) each diclazuril administration and analysed by high-pressure liquid chromatography. The mean population-derived peak concentration was 0.284μg/mL and the mean terminal hal...
Younkin JT, Santschi EM, Kukanich B, Lubbers BV, Warner M.Penicillin is administered intravenously (IV) or intramuscularly (IM) to horses for the prevention and treatment of infections, and both routes have disadvantages. To minimize these shortcomings, a 24-hr hybrid administration protocol (HPP) was developed. Our objective was to determine penicillin plasma concentrations in horses administered via HPP. Venous blood was collected from seven healthy horses administered IV potassium penicillin G at 0 and 6 hr and IM procaine penicillin G at 12 hr. Blood was collected at 2-hr intervals from 0 to 20 hr and at 24 hr. Plasma penicillin concentration...
Goodwin WA, Pasloske K, Keates HL, Ranasinghe MG, Woldeyohannes S, Perkins N.To determine the suitability of alfaxalone total intravenous (IV) anaesthesia in horses and concurrently evaluate infusion rates, cardiovascular effects, pharmacokinetics and the quality of the anaesthetic recovery period. Methods: Prospective, experimental study. Methods: Eight Standardbred horses. Methods: Horses were premedicated with IV acepromazine (0.03 mg kg) and xylazine (1 mg kg) and anaesthesia was induced with guaifenesin (35 mg kg) and alfaxalone (1 mg kg). Anaesthesia was maintained for 180 minutes using an IV infusion of alfaxalone at a rate determined by a horse's response to a ...
Hébert L, Guitton E, Madeline A, Géraud T, Carnicer D, Lakhdar L, Pitel PH, Coste M, Laloy E, Giraudet A, Zientara S, Büscher P, Laugier C, Hans A....Trypanosoma equiperdum, the causative agent of dourine, may affect the central nervous system, leading to neurological signs in infected horses. This location protects the parasite from most (if not all) existing chemotherapies. In this context, the OIE terrestrial code considers dourine as a non-treatable disease and imposes a stamping-out policy for affected animals before a country may achieve its dourine-free status. The use of practices as drastic as euthanasia remains controversial, but the lack of a suitable tool for studying a treatment's efficacy against dourine hampers the developmen...
Alvarez AV, Schumacher J, DeGraves FJ.OBJECTIVE To determine whether addition of epinephrine to a lidocaine solution would prolong and potentiate the efficacy of a palmar digital nerve block (PDNB) in horses. ANIMALS 6 adult horses with naturally occurring forefoot lameness. PROCEDURES Initially, a PDNB with a 2% lidocaine solution was performed on the affected foot of each horse. Three days later, the PDNB was repeated with a 1% lidocaine solution or a 1% lidocaine solution containing epinephrine (dilution, 1:200,000). After another 3-day washout period, the PDNB was repeated with the treatment opposite that administered for the ...
Knych HK, Mama KR, Moore CE, Hill AE, McKEMIE DS.The use of intra-articular (IA) local anaesthetics has proven to be an effective means to treat post-operative pain. The effects of local anaesthetics on equine chondrocytes are mixed with some studies reporting chondrodestruction and others no adverse effects. A liposomal formulation of bupivacaine is used in people and dogs by intra- and peri-articular administration to provide up to 72 h of analgesia. The potential uses, side effects including chondrotoxicity, and likelihood of abuse (long-term analgesic effects) has not been evaluated in horses. Objective: Describe bupivacaine concentrati...
Grubb TL, Kurkowski D, Sellon DC, Seino KK, Coffey T, Davis JL.Buprenorphine is absorbed following sublingual administration, which would be a low-stress delivery route in foals. However, the pharmacokinetics/pharmacodynamics are not described in foals. Six healthy foals <21 days of age participated in a blinded, randomized, 3-period, 5-sequence, 3-treatment crossover prospective study. Foals received 0.01-0.02 mg/kg buprenorphine administered SL or IV with an equivalent volume of saline administered by the opposite route. Blood was collected from the cephalic vein for pharmacokinetic analysis. Physiologic parameters (HR, RR, body temperature, GI sou...
Tokushige H, Kushiro A, Okano A, Maeda T, Ito H, Wakuno A, Nagata SI, Ohta M.Alfaxalone has a number of pharmacological properties which are desirable for constant rate infusion (CRI). Previously, the co-administration of alfaxalone and medetomidine is shown to be suitable for short-term anesthesia in horses. However, the use of alfaxalone-medetomidine CRI with inhalational anesthesia under surgical procedures have not been investigated in clinical cases. The aim of the present study was to evaluate the clinical efficacy of alfaxalone-medetomidine CRI in sevoflurane-anesthetized Thoroughbred racehorses undergoing arthroscopic surgery. Sevoflurane requirement, cardiovas...
Knych HK, Arthur RM, McKemie DS, Baden R, Oldberg N, Kass PH.Flumetasone is a potent corticosteroid reportedly used in horses to decrease inflammation associated with strenuous exercise. There are currently no reports describing the use of this drug in horses. Objective: To describe the pharmacokinetics and effects on cortisol and eicosanoid concentrations, following administration of flumetasone to exercised horses. Methods: Parallel design. Methods: Twelve exercised horses received a single i.v. administration of 5 mg of flumetasone. Blood and urine samples were collected before and for 72 h post-drug administration for determination of flumetasone an...
Carstensen H, Hesselkilde EZ, Fenner M, Loft-Andersen AV, Flethøj M, Kanters JK, Sattler SM, Tfelt-Hansen J, Pehrson S, Jespersen T, Buhl R.Pharmacological treatment of atrial fibrillation (AF) in horses can be challenging because of low efficacy and adverse effects. Flecainide has been tested with variable efficacy. Objective: To test whether the efficacy of flecainide is dependent on AF duration. Methods: Nine Standardbred mares. Methods: Factorial study design. All horses were instrumented with a pacemaker and assigned to a control or an AF group. On day 0, all horses were in sinus rhythm and received 2 mg/kg flecainide IV. Atrial fibrillation subsequently was induced in the AF group by pacemaker stimulation. On days 3, 9, 27, ...
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...
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...
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...
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...
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...
Lucas Castillo JA, Gozalo-Marcilla M, Werneck Fonseca M, Possebon FS, da Rosa AC, de Araujo Aguiar AJ.Information on appropriate protocols for sedation of Nordestino donkeys is scarce. Objective: To evaluate the sedative and cardiorespiratory effects of low doses of intravenous (i.v.) xylazine with and without acepromazine in 'Nordestino' donkeys. Methods: Seven healthy female Nordestino donkeys (150 ± 18 kg) were included in this blinded, randomised, crossover experiment. Methods: Four treatments were administered, consisting of two i.v. injections, at baseline (T0, 1st injection) and 15 min later (T15, 2nd injection). Treatments included acepromazine 0.05 mg/kg bwt + saline (AS), saline + x...
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...
Tavanaeimanesh H, Azarnoosh A, Ashar FS, Dehghan MM, Mohebbi Z, Akbarinejad V, Corley K.The choice of analgesic agents for the horse is limited, and many have side effects that can restrict their use for chronic and prolonged pain. Little information has been published on tramadol and acetaminophen use in the horse. The study evaluated the analgesic effects of coadministration of tramadol and acetaminophen compared to those of each drug individually in a crossover study. The study was performed on six healthy horses each infused with the following over 1 hour: control (normal saline), tramadol, acetaminophen, or both (acetaminophen and tramadol infused together). Nociception (usi...
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 ...
Knych HK, Seminoff K, McKemie DS, Kass PH.Acepromazine is a tranquilizer used commonly in equine medicine. This study describes serum and urine concentrations and the pharmacokinetics and pharmacodynamics of acepromazine following intravenous, oral, and sublingual (SL) administration. Fifteen exercised adult Thoroughbred horses received a single intravenous, oral, and SL dose of 0.09 mg/kg of acepromazine. Blood and urine samples were collected at time 0 and at various times for up to 72 hr and analyzed for acepromazine and its two major metabolites (2-(1-hydroxyethyl) promazine and 2-(1-hydroxyethyl) promazine sulfoxide) using liqu...
Alonso JM, Peccinini RG, Campos ML, Nitta TY, Akutagawa TYM, Crescencio AP, Alves ALG, Rodrigues CA, Watanabe MJ, Hussni CA.Intraperitoneal (IP) use of antimicrobial agents may lead to therapeutic effects with better clinical results than intravenous (IV) administration. The aim of this study was to compare plasma and peritoneal fluid concentrations of ceftriaxone after IP and IV administration in horses, and to evaluate possible adverse effects. One group of five horses received 25mg/kg ceftriaxone diluted in 1L saline solution by IP catheter once daily for 5 days, while a second group of five horses received 25mg/kg ceftriaxone diluted in 250mL saline solution by IV injection once daily for 5days and 1L saline so...
Scare JA, Lyons ET, Wielgus KM, Nielsen MK.Equine cyathostomin are pervasive gastrointestinal parasites with wide-spread resistance to the benzimidazole and tetrahydropyrimidine drug classes worldwide. Combination deworming has been proposed as a more sustainable parasite control strategy. Simulation studies have found combination deworming to be effective in controlling drug resistant ovine trichostrongylid parasites. One equine study demonstrated an additive effect of a combination of oxibendazole and pyrantel pamoate against cyathostomins. However, this is the only equine study evaluating combination therapy, and the effects of repe...
Davis JL, Schirmer J, Medlin E.Trazodone is a serotonin receptor antagonist and reuptake inhibitor used extensively as an anxiolytic in human and small animal veterinary medicine. The aims of this study were to determine the pharmacokinetics of oral trazodone in experimental horses and to evaluate the effect of oral trazodone in clinical horses. Six experimental horses were administered trazodone at 7.5 or 10 mg/kg. Plasma concentrations of trazodone and its metabolite (m-CPP) were determined via UPLC-MS/MS. Noncompartmental pharmacokinetic analysis, sedation and ataxia scores were determined. Trazodone was rapidly absorbe...
Berlin S, Wallstabe S, Scheuch E, Oswald S, Hasan M, Wegner D, Grube M, Venner M, Ullrich A, Siegmund W.Standard treatment of foals with severe abscessing lung infection caused by Rhodococcus equi using rifampicin and a macrolide antibiotic can be compromised by extensive inhibition and/or induction of drug metabolising enzymes (e.g. CYP3A4) and transport proteins (e.g. P-glycoprotein), as has been shown for rifampicin and clarithromycin. The combination of rifampicin with the new, poorly metabolised gamithromycin, a long-acting analogue of azithromycin and tulathromycin with lower pharmacokinetic interaction potential, might be a suitable alternative. Objective: To evaluate the pharmacokinetic ...
Monreal L, Sabaté D, Segura D, Mayós I, Homedes J.The objective was to compare the gastrointestinal and general toxicity of suxibuzone (SBZ) to that of phenylbutazone (PBZ) when administered orally in horses. Fifteen healthy horses were allocated to three treatment groups. One group received a high dose of PBZ for two weeks; the second group was given an equimolecular dosage of SBZ; and a third group received placebo. Horses were daily monitored, and blood samples were collected before and during the study. On day 18, complete post-mortem examinations were performed. One horse treated with PBZ showed clinical signs of NSAID toxicosis. Small o...
Tolliver SC, Lyons ET, Drudge JH, Stamper S, Granstrom DE.Critical tests were conducted in horses (n = 11) with naturally acquired infections of benzimidazole (BZ)-resistant population-B small strongyles in 1989 and 1990. Anthelmintics administered were thiabendazole (44 mg/kg of body weight, n = 4), oxibendazole (10 mg/kg, n = 3), and oxfendazole (OFZ, 10 mg/kg; n = 4). All compounds were paste formulations administered orally except for 1 of the OFZ treatments, which was a suspension formulation given by stomach tube. Aggregate mean efficacy was calculated for all species of small strongyles, drug-resistant and non-resistant. The highest efficacy w...
Krueger CR, Mitchell CF, Leise BS, Knych HK.Clodronate is a non-nitrogenated bisphosphonate approved for use in horses. There are no peer-reviewed published reports describing the pharmacokinetics or evaluating renal health indices and urinary excretion patterns in conjunction with plasma and synovial fluid concentration following the systemic administration of clodronate to horses. Objective: Describe clodronate concentrations in plasma, urine and synovial fluid and evaluate the effects on renal indices after intramuscular administration to healthy horses. Methods: Experimental study with repeated measures. Methods: Six healthy adult h...
Olsén L, Ingvast-Larsson C, Larsson P, Broström H, Bondesson U, Sundqvist M, Tjälve H.The pharmacokinetics and the effects on inhibition of histamine-induced cutaneous wheal formation of the histamine H1-antagonist fexofenadine were studied in horse. The effect of ivermectin pretreatment on the pharmacokinetics of fexofenadine was also examined. After intravenous infusion of fexofenadine at 0.7 mg/kg bw the mean terminal half-life was 2.4 h (range: 2.0-2.7 h), the apparent volume of distribution 0.8 L/kg (0.5-0.9 L/kg), and the total body clearance 0.8 L/h/kg (0.6-1.2 L/h/kg). After oral administration of fexofenadine at 10 mg/kg bw bioavailability was 2.6% (1.9-2.9%). Ivermect...
Ammann VJ, Vrins AA, Lavoie JP.The effects of beclomethasone dipropionate on pulmonary function and arterial blood gas values were investigated in horses with chronic obstructive pulmonary disease (COPD). Six mature mares, diagnosed as having COPD based on clinical signs, cytological examination of bronchoalveolar lavage and pulmonary function testing, were used. Beclomethasone dipropionate (3750 microg) was administered b.i.d. for a 2 week period with a metered dose inhaler using a mask. Pulmonary function tests and arterial blood gas analyses were performed at weekly intervals, starting before beclomethasone administratio...
Schwarzwald CC, Hamlin RL, Bonagura JD, Nishijima Y, Meadows C, Carnes CA.Although atrial arrhythmias are clinically important in horses, atrial electrophysiology has been incompletely studied. Objective: Standard electrophysiologic methods can be used to study drug effects in horses. Specifically, the effects of diltiazem on atrioventricular (AV) nodal conduction are rate-dependent and allow control of ventricular response rate during rapid atrial pacing in horses undergoing quinidine treatment. Methods: Fourteen healthy horses. Methods: Arterial blood pressure, surface electrocardiogram, and right atrial electrogram were recorded during sinus rhythm and during pro...
Gozalo-Marcilla M, Gasthuys F, Luna SPL, Schauvliege S.The objective of this review was to perform a literature compilation of all the equine publications that used dexmedetomidine as the first article on this topic was published, in 2005. We also aimed to answer the question whether the use of dexmedetomidine can currently be justified. For that, we compiled information from databases, such as PubMed, Google Scholar and Web of Science and the proceedings of the last veterinary anaesthesiology meetings. Dexmedetomidine is an attractive drug to be used in horses, mainly due to its pharmacokinetic profile and pharmacodynamics that favour its use as ...
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.
Baggot JD.Veterinary and human pharmacology differ principally in the range of species in which drugs are used and studied. In animals, as in humans, an understanding of the dose-effect relationship can be obtained by linking pharmacokinetic behaviour with pharmacodynamic information. Studies of different classes of drugs support the assumption that the range of therapeutic plasma concentrations in animals is generally the same as in humans. The requirement for species differences in dosage or administration rate (dose/dosage interval) may be attributed to variations in pharmacokinetic behaviour or phar...
Goodwin W, Keates H, Pasloske K, Pearson M, Sauer B, Ranasinghe MG.To determine the pharmacokinetics and pharmacodynamics of the neurosteroid anaesthetic, alfaxalone, in neonatal foals after a single intravenous (IV) injection of alfaxalone following premedication with butorphanol tartrate. Methods: Prospective experimental study. Methods: Five clinically healthy Australian Stock Horse foals of mean ± SD age of 12 ± 3 days and weighing 67.3 ± 12.4 kg. Methods: Foals were premedicated with butorphanol (0.05 mg kg(-1) IV) and anaesthesia was induced 10 minutes later by IV injection with alfaxalone 3 mg kg(-1) . Cardiorespiratory variables (pulse rate, respir...
Bauquier JR, Boston RC, Sweeney RW, Wilkins PA, Nolen-Walston RD.Gentamicin is an aminoglycoside antimicrobial commonly used in horses at 6.6 mg/kg IV once daily. Therapeutic drug monitoring (TDM) can confirm desired peak concentration is reached for common bacterial isolates, and detect toxicosis associated with high trough values. Objective: Determine the relationship between gentamicin dose and plasma concentration in hospitalized horses, and identify a starting dose range to achieve peaks > 32 μg/mL. Methods: Sixty-five horses (2002-2010) receiving once-daily gentamicin with TDM performed (N = 99 sets). Methods: Retrospective study. Data from hospit...
Larenza MP, Landoni MF, Levionnois OL, Knobloch M, Kronen PW, Theurillat R, Schatzmann U, Thormann W.The arterial pharmacokinetics of ketamine and norketamine enantiomers after racemic ketamine or S-ketamine i.v. administration were evaluated in seven gelding ponies in a crossover study (2-month interval). Methods: Anaesthesia was induced with isoflurane in oxygen via a face-mask and then maintained at each pony's individual MAC. Racemic ketamine (2.2 mg kg(-1)) or S-ketamine (1.1 mg kg(-1)) was injected in the right jugular vein. Blood samples were collected from the right carotid artery before and at 1, 2, 4, 8, 16, 32, 64, and 128 min after ketamine administration. Ketamine and norketamine...
Venner M, Peters J, Höhensteiger N, Schock B, Bornhorst A, Grube M, Adam U, Scheuch E, Weitschies W, Rosskopf D, Kroemer HK, Siegmund W.Macrolide antibiotics penetrate in the lung against steep concentration gradients into the epithelial lining fluid (ELF) and broncho-alveolar cells (BAC). Since they interact with ABCB1, ABCC2, and organic anion transporting proteins (OATPs), which are localized to lung tissue, pulmonary concentration may be influenced by rifampicin (RIF), an inducer and modulator of efflux and uptake transporters. We measured concentrations of tulathromycin (TM) in plasma, ELF and BAC in 21 warm-blooded foals 24 and 192 h after first and last intramuscular injection of 2.5 mg/kg TM once weekly for 6 weeks. In...
Tapio H, Raekallio MR, Mykkänen A, Männikkö S, Scheinin M, Bennett RC, Vainio O.Medetomidine suppresses cardiovascular function and reduces gastrointestinal motility in horses mainly through peripheral α -adrenoceptors. Vatinoxan, a peripheral α -antagonist, has been shown experimentally to alleviate the adverse effects of some α -agonists in horses. However, vatinoxan has not been investigated during constant-rate infusion (CRI) of medetomidine in standing horses. Objective: To evaluate effects of vatinoxan on cardiovascular function, gastrointestinal motility and on sedation level during CRI of medetomidine. Methods: Experimental, randomised, blinded, cross-over stud...
Baggot JD.The route of administration and formulation of the dosage form affect the bioavailability (rate and extent of absorption) of a drug and may thereby influence the intensity and duration of the pharmacological effect. Location of injection site may affect the plasma concentration profile of drugs administered as aqueous suspensions or sustained release parenteral preparations (procaine penicillin G). When absorption influences the rate of elimination ('flip-flop' phenomenon), the apparent half-life of the drug will be increased (cefazolin sodium, i.m.; meclofenamic acid, p.o.). Absorption genera...
van Nieuwstadt RA, Henricks PA, Hajer R, van der Meer van Roomen WA, Breukink HJ, Nijkamp FP.This study was undertaken to assess the importance of muscarinic receptor subtypes in equine airway disease. Smooth muscle strips from the mid-cervical portion of the trachea of horses were placed in tissue baths and isometric contractile force was measured. Active force was measured in response to metacholine and the selective muscarinic receptor agonists McN-A-343 (M1-selective) and pilocarpine (M2-selective) in cumulative concentrations (10(-9)M through 10(-3)M), with and without preincubation with three or four concentrations of the selective muscarinic receptor antagonists pirenzepine (M1...
Clark JO, Clark TP.Critical to reducing patient morbidity as well as heightened ethical awareness, alleviation of pain in animals has become integral to medical case management and surgical procedures. Pharmacotherapy is directed at peripheral nociceptors, primary and secondary spinal neurons, and pain-processing areas in the CNS. Accordingly, three primary pharmacologic strategies have evolved: drugs that bind to and activate opioid receptors, drugs that bind to and activate alpha 2 receptors, and drugs that reduce de novo prostaglandin synthesis. In horses, the two predominant types of pain encountered are mus...
Knych HK, Stanley SD, Arthur RM, Mitchell MM.The use of firocoxib in horses and its ability to affect performance and potential to allow a horse to compete when it otherwise should not, necessitates establishing appropriate withdrawal time guidelines prior to performance. Objective: To describe plasma concentrations and characterise the pharmacokinetics of 3 firocoxib formulations following multiple administrations of the label dose, with respect to recommended plasma thresholds for performance horses. Methods: Balanced 3-way crossover prospective study. Methods: Nine healthy mature horses were administered firocoxib injectable solution ...
Beccar-Varela AM, Epstein KL, White CL.To determine the effects of experimentally induced synovitis of the radiocarpal joint on the intra-articular pharmacokinetics and pharmacodynamics of amikacin after intravenous regional limb perfusion (IVRLP). Methods: Randomized crossover experimental design. Methods: Adult horses (n = 8). Methods: Horses were randomly assigned into 2 trials: synovitis and no-synovitis. Radiocarpal joint synovitis was induced with lipopolysaccharide 6 hours before IVRLP. IVRLP (5-mg/kg amikacin qs 60 mL) was performed with a pneumatic tourniquet under general anesthesia. Synovial fluid was obtained before and...
Winther L, Baptiste KE, Friis C.Cefquinome concentrations, following intravenous and aerosol administration to horses, in pulmonary epithelial lining fluid (PELF) were examined and compared to plasma concentrations. Single dose of cefquinome sulphate (1 mg/kg) was administered intravenously to six horses followed by a single aerosol administration (225 mg) with a wash-out period of 14 days between treatments. After each drug administration, cefquinome concentrations in plasma and PELF, obtained by intrabronchial cotton swabs, were determined. After intravenous administration, cefquinome concentrations in plasma declined fast...
Fenner MF, Gatta G, Sattler S, Kuiper M, Hesselkilde EM, Adler DMT, Smerup M, Schotten U, Sørensen U, Diness JG, Jespersen T, Verheule S....Small-conductance Ca2+-activated K+ (KCa2) channels have been proposed as a possible atrial-selective target to pharmacologically terminate atrial fibrillation (AF) and to maintain sinus rhythm. However, it has been hypothesized that the importance of the KCa2 current-and thereby the efficacy of small-conductance Ca2+-activated K+ current (I K,Ca) inhibition-might be negatively related to AF duration and the extent of AF-induced remodeling. Unassigned: To address the hypothesis of the efficacy of I K,Ca inhibition being dependent on AF duration, the anti-arrhythmic properties of the I K,Ca inh...
Vainionpää MH, Raekallio MR, Pakkanen SA, Ranta-Panula V, Rinne VM, Scheinin M, Vainio OM.To investigate plasma drug concentrations and the effect of MK-467 (L-659'066) on sedation, heart rate and gut motility in horses sedated with intravenous (IV) detomidine. Methods: Experimental randomized blinded crossover study. Methods: Six healthy horses. Methods: Detomidine (10 μg kg(-1) IV) was administered alone (DET) and in combination with MK-467 (250 μg kg(-1) IV; DET + MK). The level of sedation and intestinal sounds were scored. Heart rate (HR) and central venous pressure (CVP) were measured. Blood was collected to determine plasma drug concentrations. Repeated measures anova was ...
Semrad SD, Hardee GE, Hardee MM, Moore JN.The pharmacokinetics and inhibition of prostaglandin synthesis in conscious horses given various dosages of flunixin meglumine were studied. Plasma concentrations of flunixin were measured by high-performance liquid chromatography, and serum thromboxane B2 and 6-keto prostaglandin F1 alpha were quantitated by radioimmunoassay. Within the dosage range studied, linear pharmacokinetics were achieved. After IV administration of flunixin (1.1 mg/kg, 0.25 mg/kg, 0.1 mg/kg), significant suppression of serum thromboxane generation persisted for 12, 4, and 3 hours, respectively. Repeated administration...
Maitho TE, Lees P, Taylor JB.The disposition of phenylbutazone (4.4 mg/kg), administered intravenously to six Welsh Mountain ponies, was described by a two-compartment open model. Pharmacokinetic parameters were not significantly different after morning dosing in comparison with afternoon dosing. When phenylbutazone (4.4 mg/kg) was administered orally to the same ponies, marked variations in time to peak concentrations were produced with different feeding schedules. When access to hay was permitted before and after dosing, the mean time to peak concentration was 13.2 +/- 1.2 h and double peaks in the plasma concentration-...
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 ...
Johnstone IB.Nonsteroidal anti-inflammatory drugs are commonly used in the treatment of inflammatory conditions, and have potential value in the treatment of thrombotic disease in the horse. This study compares the potency of three nonsteroidal anti-inflammatory drugs phenylbutazone, naproxen (equiproxen) and flunixin meglumine (banamine) with respect to their effects on equine platelets. Two functional responses of horse platelets were evaluated in vitro: their ability to aggregate and their ability to make available platelet factor 3 procoagulant activity. Flunixin at a concentration of 10(-6) M signific...
Pille F, De Baere S, Ceelen L, Dewulf J, Croubels S, Gasthuys F, De Backer P, Martens A.To determine radiocarpal (RC) joint synovial fluid and plasma ceftiofur concentrations after regional intravenous perfusion (RIP) and systemic intravenous (IV) administration. Methods: Experimental cross-over study. Methods: Five normal adult horses. Methods: One RC joint was randomly selected for RIP and the contralateral RC joint was sampled to determine intrasynovial ceftiofur concentrations after IV administration. Wash-out between IV and RIP was > or = 14 days. After surgical introduction of an intraarticular catheter, ceftiofur (2 g) was administered under general anesthesia either IV or...
Knych HK, Casbeer HC, McKemie DS, Arthur RM.Butorphanol is a narcotic analgesic commonly used in horses. Currently, any detectable concentration of butorphanol in biological samples collected from performance horses is considered a violation. The primary goal of the study reported here was to update the pharmacokinetics of butorphanol following intravenous administration, utilizing a highly sensitive liquid chromatography-mass spectrometry (LC-MS) assay that is currently employed in many drug-testing laboratories. An additional objective was to characterize behavioral and cardiac effects following administration of butorphanol. Ten exer...
Cornelisse CJ, Robinson NE, Berney CE, Kobe CA, Boruta DT, Derksen FJ.Although the efficacy of dexamethasone for the treatment of recurrent airway obstruction (RAO) has been documented, the speed of onset of effect and duration of action are unknown, as is the efficacy of orally administered dexamethasone with or without fasting. Objective: To document the time of onset of effect and duration of action of a dexamethasone solution i.v. or orally with and without fasting. Methods: Protocol 1 used 8 RAO-affected horses with airway obstruction in a crossover design experiment that compared the effect of i.v. saline and dexamethasone (0.1 mg/kg bwt) on pulmonary func...
Scare JA, Lyons ET, Wielgus KM, Nielsen MK.Equine cyathostomin are pervasive gastrointestinal parasites with wide-spread resistance to the benzimidazole and tetrahydropyrimidine drug classes worldwide. Combination deworming has been proposed as a more sustainable parasite control strategy. Simulation studies have found combination deworming to be effective in controlling drug resistant ovine trichostrongylid parasites. One equine study demonstrated an additive effect of a combination of oxibendazole and pyrantel pamoate against cyathostomins. However, this is the only equine study evaluating combination therapy, and the effects of repe...
