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.
Ohmura H, Okano A, Mukai K, Fukuda K, Takahashi T.This study evaluated induction of anesthesia and cardiorespiratory and anesthetic effects during maintained anesthesia with the combination of alfaxalone, medetomidine, and butorphanol. Alfaxalone (1.0 mg/kg) was administered to induce anesthesia after premedication with medetomidine (7.0 µg/kg), butorphanol (25 µg/kg), and midazolam (50 µg/kg) in six Thoroughbred horses. Intravenous general anesthesia was maintained with alfaxalone (2.0 mg/(kg∙hr)), medetomidine (5.0 µg/(kg∙hr)), and butorphanol (30 µg/(kg∙hr)) for 60 min. Electrical stimulation of the upper oral mucosa was used to...
Haspeslagh M, Taevernier L, Maes AA, Vlaminck LE, De Spiegeleer B, Croubels SM, Martens AM.Topical acyclovir application is an owner-friendly treatment for occult equine sarcoids, without the caustic side-effects other topical treatments have. Variable clinical success rates have been described, but it is not known to what rate and extent acyclovir penetrates in and through equine skin from a topical formulation. In the current study, an in vitro Franz diffusion model was used to determine the permeation parameters for a generic 5% acyclovir cetomacrogol cream for both healthy and sarcoid equine skin. The distribution of acyclovir between different layers of both skin types was also...
Knych HK, Steffey EP, White AM, McKemie DS.Tramadol is an analgesic agent used in man and a number of veterinary species. The pharmacokinetics and behavioural effects of tramadol and its active metabolite have been described in mature horses, but not in young foals. Objective: To characterise the pharmacokinetics, metabolism and some induced behavioural and physiological responses following i.v. tramadol administration in the same group of foals on 4 different occasions, from a few days after birth to age 43 days. Methods: Experimental. Methods: Tramadol was administered i.v. (3 mg/kg bwt) to a group of 8 foals on 4 separate occasion...
Del Río-Sancho S, Concas D, Oreste P, Zoppetti G, Briggs PH, Kalia YN.The aim was to investigate diclofenac delivery into and across equine skin in vitro using Franz diffusion cells from a novel diclofenac epolamine (DIC-EP; 1.3%) formulation and to compare the results to those of Surpass (1% diclofenac sodium liposomal cream) and a 1% aqueous solution of diclofenac sodium. Skin was harvested from the lower legs of Freiberger geldings immediately after slaughter and sliced to a thickness of ~2 mm. Skin samples were divided into two groups [Group 1: 1 year old (n = 2) and Group 2: 6-8 years old (n = 3)]. Cumulative permeation of diclofenac in Groups 1 and...
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.
Gokbulut C, Ozuicli M, Aksit D, Aksoz E, Korkut O, Yalcinkaya M, Cirak VY.The horse milk gains increasing interest as a food product for sensitive consumers, such as children with food allergies or elderly people. We investigated the plasma and milk disposition, faecal excretion and efficacy of per os ivermectin (IVM) and pour-on eprinomectin (EPM) in horses. Ten mares were divided into two groups. The equine paste formulation of IVM and bovine pour-on formulation of EPM were administered orally and topically at dosage of 0.2 and 0.5 mg/kg bodyweight. Blood, milk and faecal samples were analysed using high-performance liquid chromatography. The plasma concentration...
Nakayama SM, Ikenaka Y, Hayami A, Mizukawa H, Darwish WS, Watanabe KP, Kawai YK, Ishizuka M.Research on drug metabolism and pharmacokinetics in large animal species including the horse is scarce because of the challenges in conducting in vivo studies. The metabolic reactions catalyzed by cytochrome P450s (CYPs) are central to drug pharmacokinetics. This study elucidated the characteristics of equine CYPs using diazepam (DZP) as a model compound as this drug is widely used as an anesthetic and sedative in horses, and is principally metabolized by CYPs. Diazepam metabolic activities were measured in vitro using horse and rat liver microsomes to clarify the species differences in enzy...
Knych HK, Stanley SD, Seminoff KN, McKemie DS, Kass PH.Methocarbamol (MCBL) is commonly used in performance horses for the treatment of skeletal muscle disorders. Current regulatory recommendations for show horses and racehorses are based on a single oral dose of 5 g, although doses in excess of this are often administered. The goal of the current study was to characterize the disposition of MCBL following higher dose administration and administration in combination with another commonly used drug in performance horses, phenylbutazone (PBZ). Exercised Thoroughbred horses were administered various doses of MCBL as a sole agent and MCBL in combinat...
de Vries A, Pakkanen SA, Raekallio MR, Ekiri A, Scheinin M, Taylor PM, Vainio OM.To investigate the effects of MK-467 on sedation quality, and cardiopulmonary and pharmacokinetic variables in horses sedated intravenously (IV) with romifidine. Methods: Experimental, randomized, crossover design. Methods: Seven healthy mares. Methods: Romifidine (80 μg kg-1 ; R) and MK-467 (200 μg kg-1 ; MK) were administered IV alone and in combination (R + MK). Levels of sedation and borborygmi were scored. Heart rate (HR), direct arterial blood pressure (ABP) and respiratory rate (fR ) were recorded. Arterial and venous blood gas analyses were performed and venous plasma drug conc...
Handing KB, Shabalin IG, Szlachta K, Majorek KA, Minor W.Serum albumin (SA) is the main transporter of drugs in mammalian blood plasma. Here, we report the first crystal structure of equine serum albumin (ESA) in complex with antihistamine drug cetirizine at a resolution of 2.1Å. Cetirizine is bound in two sites--a novel drug binding site (CBS1) and the fatty acid binding site 6 (CBS2). Both sites differ from those that have been proposed in multiple reports based on equilibrium dialysis and fluorescence studies for mammalian albumins as cetirizine binding sites. We show that the residues forming the binding pockets in ESA are highly conserved in h...
Berlin S, Spieckermann L, Oswald S, Keiser M, Lumpe S, Ullrich A, Grube M, Hasan M, Venner M, Siegmund W.Drug interactions often result from multiple pharmacokinetic changes, such as after rifampicin (RIF) and clarithromycin (CLA) in the treatment of abscessing lung diseases. Comedication of RIF may interact with CLA disposition by either induction of presystemic elimination processes and/or inhibition of uptake mechanisms because it regulates gene transcription and modulates function of various CYP enzymes, multidrug efflux and uptake transporters for which CLA is a substrate. To distinguish the transcriptional changes from the modulating interaction components upon CLA absorption and pulmonary ...
Knych HK, Stanley SD, Benson D, Arthur RM.Guaifenesin is an expectorant commonly used in performance horses to aid in the clearance of mucus from the airways. Guaifenesin is also a centrally acting skeletal muscle relaxant and as such is a prohibited drug with withdrawal necessary prior to competition. To the authors' knowledge, there are no reports in the literature describing single or multiple oral administrations of guaifenesin in the horse to determine a regulatory threshold and related withdrawal time. Therefore, the objective of the current study was to describe the pharmacokinetics of guaifenesin following oral administration ...
Mas M, Mañé N, Fernández F, Gallego D, Pumarola M, Jiménez M.In the equine large intestine, the knowledge of the basic mechanisms underlying motility function is crucial to properly treat motility disorders. P2Y1 receptors are responsible for mediating purinergic colonic relaxation in several species. In vitro experimental studies of the circular muscle from the equine pelvic flexure (n = 6) were performed to characterize inhibitory and excitatory neuromuscular transmission. Electrophysiological studies showed that electrical field stimulation (EFS) evoked biphasic inhibitory junction potentials (IJPs) in smooth muscle cells: a fast IJP (IJPf) follo...
Marly-Voquer C, Schwarzwald CC, Bettschart-Wolfensberger R.Five horses were presented for treatment of atrial fibrillation by transvenous electrical cardioversion (TVEC). A dexmedetomidine infusion was administered for sedation during positioning of the cardioversion catheters, and continued during general anesthesia. Shocks were applied until return to sinus rhythm. Dexmedetomidine infusion provided excellent conditions for TVEC catheter placement and procedure. Utilisation d’une perfusion continue de dexmedetomidine lors de cardioversion électrique transveineuse chez le cheval: une série de cas. Cinq chevaux présentant une fibrillation atriale ...
Knych HK, Vidal MA, Chouicha N, Mitchell M, Kass PH.The frequent use of intra-articular triamcinolone acetonide (TA) in performance horses warrants further study of the duration of as well as the beneficial and detrimental effects on gene expression associated with administration. Objective: To assess the effects of intra-articular administration of TA on the expression of selected anti- and proinflammatory and structural matrix genes following its administration into joints of exercised Thoroughbred horses and to correlate these effects with plasma and synovial fluid drug concentrations. Methods: Block design experiment. Methods: Eight exercis...
Edwards-Milewski ML, Morello SL, Zhao Q, Mattan-Bell C.To compare the gross and histological effects of intravenous regional limb perfusion (IVRLP) using amikacin sulfate on second intention healing of distal limb wounds in adult horses with healing in untreated wounds. Methods: In vivo experimental study. Methods: Adult horses (n = 7). Methods: Two full thickness wounds (2.5 × 2.5 cm) were created aseptically on the dorsal aspect of each metacarpus and maintained under sterile bandages. One forelimb was randomly selected from each horse for IVRLP on days 2, 3, and 4 post-wounding. Sequential biopsies were taken from 1 wound on each limb to evalu...
Gokbulut C, Aksit D, Santoro M, Roncoroni C, Mariani U, Buono F, Rufrano D, Fagiolo A, Veneziano V.Mebendazole (MBZ) has been licensed for use in horses and donkeys, however there are no data available in the literature regarding its pharmacokinetic disposition and efficacy in donkeys. This study was designed to determine the plasma disposition, milk excretion and anthelmintic efficacy of MBZ in donkeys naturally infected by Cyathostominae. The animals were allocated to three groups, each of six donkeys. One group was untreated control (C-group) and the others were treated using a paste formulation of MBZ administered per os at the manufacturer's recommended horse dosage of 10 mg/kg body we...
Cohen ND, Giguère S, Burton AJ, Rocha JN, Berghaus LJ, Brake CN, Bordin AI, Coleman MC.Adverse effects of, and bacterial resistance to, macrolides used to treat Rhodococcus equi infections have prompted search for clinically effective alternative antimicrobials. Liposomal gentamicin (LG) is effective against R. equi in vitro and decreases tissue concentrations of R. equi in experimentally infected mice. Effectiveness of LG treatment of foals with R. equi pneumonia, however, has not been described. Objective: Liposomal gentamicin is safe and effective for treating foals with R. equi pneumonia. Methods: Ten foals with experimentally induced R. equi pneumonia. Methods: Pilot treatm...
Kinobe RT.Cobalt is an essential trace element for many vital physiological functions. Cobalt is also known to stabilise hypoxia-inducible transcription factors leading to increased expression of erythropoietin which activates production of red blood cells. This implies that cobalt can be used to enhance aerobic performance in racing horses. If this becomes a pervasive practice, the welfare of racing animals would be at risk because cobalt is associated with cardiovascular, haematological, thyroid gland and reproductive toxicity as observed in laboratory animals and humans. It is expected that similar e...
Chan GH, Ho EN, Leung DK, Wong KS, Wan TS.The use of anabolic androgenic steroids (AAS) is prohibited in both human and equine sports. The conventional approach in doping control testing for AAS (as well as other prohibited substances) is accomplished by the direct detection of target AAS or their characteristic metabolites in biological samples using hyphenated techniques such as gas chromatography or liquid chromatography coupled with mass spectrometry. Such an approach, however, falls short when dealing with unknown designer steroids where reference materials and their pharmacokinetics are not available. In addition, AASs with fast...
Barton MH, Darden JE, Clifton S, Vandenplas M.To validate primer sets for use in reverse transcription quantitative PCR assays to measure gene expression of cytosolic phospholipase A2 (cPLA2) and microsomal prostaglandin E2 synthase 1 (mPGES1) in equine mononuclear cells and determine the effects of firocoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, on COX-2, cPLA2, and mPGES1 gene expression following incubation of mononuclear cells with lipopolysaccharide (LPS). Methods: 8 healthy adult horses. Methods: Peripheral blood mononuclear cells were isolated by density gradient centrifugation and incubated at 37°C with medium alone, f...
Fischer B, Clark-Price S.Anesthetizing the neonatal foal presents significant challenges as a result of physiologic differences from the adult equine. This article gives the reader an overview of these differences and the impact they have on anesthetic drug selection, monitoring, and support of the equine neonate. Special emphasis is directed to the sick neonate and appropriate preparation and maintenance of anesthesia in the face of commonly presented disease conditions.
Aristizabal FA, Nieto JE, Guedes AG, Dechant JE, Yamout S, Morales B, Snyder J.Regional limb perfusion (RLP) in horses has proven to be a simple and effective technique for the treatment of synovial and musculoskeletal infections in the distal portion of the limbs. The ideal tourniquet time needed to achieve therapeutic synovial concentrations remains unknown. The pharmacokinetic effects of general anesthesia (GA) versus standing sedation (SS) RLP on synovial amikacin concentrations are not completely understood. This study investigated the pharmacokinetic effects of RLP under general anesthesia (GA) versus standing sedation (SS) on synovial amikacin concentration follow...
Ekstrand C, Ingvast-Larsson C, Olsén L, Hedeland M, Bondesson U, Gabrielsson J.The cortisol response to glucocorticoid intervention has, in spite of several studies in horses, not been fully characterized with regard to the determinants of onset, intensity and duration of response. Therefore, dexamethasone and cortisol response data were collected in a study applying a constant rate infusion regimen of dexamethasone (0.17, 1.7 and 17 μg/kg) to six Standardbreds. Plasma was analysed for dexamethasone and cortisol concentrations using UHPLC-MS/MS. Dexamethasone displayed linear kinetics within the concentration range studied. A turnover model of oscillatory behaviour accu...
Kusano K, Nomura M, Toju K, Ishikawa Y, Minamijima Y, Yamashita S, Nagata S.Procaterol (PCR) is a beta-2-adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 μg/kg) and oral (2.0 μg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography-mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady-state volume of the distribution was 1.21 ± 0.23 L/kg, ...
Serrano-Rodríguez JM, Gómez-Díez M, Esgueva M, Castejón-Riber C, Mena-Bravo A, Priego-Capote F, Serrano Caballero JM, Muñoz A.The pharmacokinetics and pharmacodynamics (PK/PD) of the angiotensin-converting enzyme inhibitor (ACEI) ramiprilat after intravenous (IV) and oral (PO) administration of ramipril have not been evaluated in horses. This study was designed to establish PK profiles for ramipril and ramiprilat as well as to determine the effects of ramiprilat on serum angiotensin converting enzyme (ACE) and to select the most appropriate ramipril dose that suppresses ACE activity. Six healthy horses in a cross-over design received IV ramipril 0.050 mg/kg, PO at a dose of 0 (placebo), and 0.050, 0.10, 0.20, 0.40 ...
Sole A, Nieto JE, Aristizabal FA, Snyder JR.Emptying the vasculature with an Esmarch bandage before i.v. regional anaesthesia is commonly performed in human patients to prevent leakage of the solution under the tourniquet but there is no evidence for its efficacy in horses for antimicrobial i.v. regional limb perfusion (IV-RLP). Objective: To determine the effect on synovial fluid concentration of amikacin of emptying the vasculature before performing IV-RLP. Methods: Crossover experiment. Methods: Eight clinically healthy horses underwent 2 IV-RLP with amikacin in a randomised, crossover design. Horses received an IV-RLP with amikacin ...
Corado CR, McKemie DS, Young A, Knych HK.Metabolism is an essential factor in the clearance of many drugs and as such plays a major role in the establishment of dosage regimens and withdrawal times. CYP2D6, the human orthologue to equine CYP2D50, is a drug-metabolizing enzyme that is highly polymorphic in humans leading to widely differing levels of metabolic activity. As CYP2D6 is highly polymorphic, in this study it was hypothesized that the gene coding for the equine orthologue, CYP2D50, may also be prone to polymorphism. Blood samples were collected from 150 horses, the CYP2D50 gene was cloned and sequenced; and full-length seque...
Broux B, De Clercq D, Decloedt A, De Baere S, Devreese M, Van Der Vekens N, Ven S, Croubels S, van Loon G.Arrhythmias are common in horses. Some, such as frequent atrial or ventricular premature beats, may require long-term anti-arrhythmic therapy. In humans and small animals, sotalol hydrochloride (STL) is often used for chronic oral anti-arrhythmic therapy. STL prolongs repolarization and the effective refractory period in all cardiac tissues. No information on STL pharmacokinetics or pharmacodynamics in horses is available and the aim of this study was to evaluate the pharmacokinetics of intravenously (IV) and orally (PO) administered STL and the effects on surface electrocardiogram and left ve...
Wang CC, Hartmann-Fischbach P, Krueger TR, Wells TL, Feineman AR, Compton JC.3,4-Methylenedioxypyrovalerone (MDPV) is a psychoactive drug with potent stimulant properties and potential for abuse and drug dependency. MDPV was recently classified as a Class I drug by Racing Commissioners International, indicating that it is a banned substance in equine athletes because it lacks therapeutic value in horses. To enforce this ban, a sensitive and fast liquid chromatography-tandem mass spectrometry method was needed. It is for this reason that this method was developed for quantification and confirmation of MDPV in equine plasma. Sample preparation involved liquid-liquid extr...
Rubio-Martínez LM, López-Sanromán J, Cruz AM, Tendillo F, Rioja E, San Román F.To evaluate the clinical effects and pharmacokinetics of vancomycin in plasma and synovial fluid after intraosseous regional limb perfusion (IORLP) in horses and to compare results with those obtained after IV regional limb perfusion (IVRLP). Methods: 6 horses. Methods: 1 forelimb of each horse received vancomycin hydrochloride (300 mg in 60 mL of saline [0.9% NaCl] solution) via IORLP; the contralateral limb received 60 mL of saline solution (control). Solutions were injected into the medullary cavity of the distal portion of the third metacarpal bone. Synovial fluid from the metacarpophalang...
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...
Pérez R, Godoy C, Palma C, Cabezas I, Muñoz L, Rubilar L, Arboix M, Alvinerie M.A study was undertaken in order to evaluate and compare ivermectin's (IVM) plasma disposition kinetic parameters after oral or intramuscular (IM) administration in horses. Ten clinically healthy adult horses, weighing 380-496 kg body weight (BW), were allocated to two experimental groups of five horses. Group I, was treated with an oral paste formulation of IVM at the manufacturer's recommended dose of 0.2 mg/kg BW. Group II, was treated IM with an injectable 1% formulation of IVM at a dose of 0.2 mg/kg BW. Blood samples were collected by jugular puncture at different times between 0.5 h and 7...
Leathwick DM, Sauermann CW, Geurden T, Nielsen MK.A previously described model for the dynamics of the parasitic stages of Parascaris spp. was modified to include eggs outside the host and the genetics of anthelmintic resistance before being used to address questions regarding the development of resistance. Three broad questions were addressed; i) How sustainable is the current common practice of treating foals monthly for their first year of life (i.e. 12 treatments/year)? ii) Does the timing of treatments have an effect on resistance development? (i.e. do certain treatments select for resistance more strongly than others?), and iii) How sus...
Peterbauer C, Larenza PM, Knobloch M, Theurillat R, Thormann W, Mevissen M, Spadavecchia C.To investigate the effect of plasma concentrations obtained by a low dose constant rate infusion (CRI) of racemic ketamine or S-ketamine on the nociceptive withdrawal reflex (NWR) in standing ponies. Methods: Prospective, blinded, cross-over study. Methods: Six healthy 5-year-old Shetland ponies. Methods: Ponies received either 0.6 mg kg(-1) racemic ketamine (group RS) or 0.3 mg kg(-1) S-ketamine (group S) intravenously (IV), followed by a CRI of 20 microg kg(-1)minute(-1) racemic ketamine (group RS) or 10 microg kg(-1)minute(-1) S-ketamine (group S) for 59 minutes. The NWR was evoked by trans...
Nieto JE, Snyder JR, Kollias-Baker C, Stanley S.To determine effects of cisapride and 5-hydroxytryptamine (5-HT) on the jejunum of horses. Methods: Jejunal muscle strips from 8 horses. Methods: Muscle strips were suspended in isolated muscle baths. Isometric stress responses to 5-HT and cisapride, with and without specific antagonists, were determined. Results: Muscle strips incubated with atropine and tetrodotoxin responded to 5-HT and cisapride with an increase in contractile force. The 5-HT caused a concentration-dependent increase in contractile amplitude, with a maximum response (Emax) of 1,151+/-214 g/cm2 and a molar concentration tha...
Cox KS, Nelson BB, Wittenburg L, Gold JR.Regional limb perfusion (RLP) is an effective treatment option for injuries and infections of the distal limb in horses. Using ceftiofur sodium in RLP has been studied due to its superior spectrum of Gram-positive organisms compared to aminoglycosides, but it is not known if this antimicrobial drug adequately penetrates subcutaneous tissue and bone. Objective: To determine the concentration of ceftiofur in plasma, subcutaneous tissue and bone in horses after RLP. Methods: Experimental prospective study. Methods: Six healthy horses were used in this study. Under standing sedation, an Esmarch to...
Valk N, Doherty TJ, Blackford JT, Abraha TW, Frazier DL.The effect of cisapride pretreatment on gastric emptying in horses was determined by measuring serum concentrations of acetaminophen, a drug known to be readily absorbed in the small intestine but not in the stomach. The time to reach maximum serum acetaminophen concentrations (Tmax), the maximum serum concentrations (Cmax) and the area under the serum acetaminophen concentration vs. time curves (AUC) were compared among treatment groups. In the first part of the study, the effect of orally administered cisapride (0.1, 0.2 and 0.4 mg/kg bwt) on gastric emptying was examined in 6 normal fasted ...
Boyer S, Garcia P, Popot MA, Steiner V, Lesieur M.A sensitive and specific method has been developed to detect semi-quantitatively testosterone in horse hair samples. The method involved a washing step with sodium dodecylsulfate aqueous solution. The mane and tail hair samples (100mg) were dissolved in 1 mL of sodium hydroxide for 15 min at 95 degrees C in the presence of d3-boldenone used as internal standard. The next three steps involved diethyl ether extraction and a solid phase extraction on Isolute C18 (EC) cartridges eluted with methanol. The residue was derivatized by adding 100 microL of acetonitrile and 30 microL of PFPA then incuba...
Tevell A, Bondesson U, Törneke K, Hedeland M.The metabolism of clemastine was studied in dogs, horses, and humans after a single dose of Tavegyl. The urine collected was extracted by solid-phase extraction or hydrolyzed with beta-glucuronidase and then extracted by liquid-liquid extraction, prior to analysis for unchanged drug and phase I and II metabolites by liquid chromatography/tandem mass spectrometry. The metabolites were identified by their molecular mass and interpretation of the product ion spectra, since no standard substances were available. Unchanged drug was recovered in urine samples from dogs and humans, but not from horse...
Scofield D, Black J, Wittenburg L, Gustafson D, Ferris R, Hatzel J, Traub-Dargatz J, McCue P.Systemic administration of ceftiofur crystalline free acid (CCFA) may be a potential treatment for infectious endometritis caused by Streptococcus equi ssp. zooepidemicus (S. zooepidemicus) and other susceptible bacterial organisms in the mare. Objective: To determine if i.m. administration of CCFA at the label dose will exceed the minimum inhibitory concentration (MIC) of S. zooepidemicus in the endometrium following single administration and multiple administration protocols. Methods: Experimental pharmacokinetic study. Methods: Three mares (Group 1) were administered a single i.m. dos...
Peyrou M, Doucet MY, Vrins A, Concordet D, Schneider M, Bousquet-Mélou A.Population pharmacokinetic of marbofloxacin was investigated on 21 healthy and 16 diseased horses to assess interindividual variability of drug exposure. Demographic, physiologic and disease covariables were tested using mixed effects models. As a preliminary analysis, this study has demonstrated that none of the tested covariables were significant in regression models for compartmental volumes or clearance of distribution, but the clinical status of the horse (healthy/diseased) was a significant covariable (P < 0.01) for systemic clearance. Clearance had a lower mean and a higher variance ...
French K, Pollitt CC, Pass MA.Experiments were performed to establish the pharmacokinetics of triamcinolone acetonide and the effects of the glucocorticoid on glucose metabolism in horses. The pharmacokinetics after intravenous (i.v.) dosing was best described by a three-compartment open model. There was rapid distribution from the central compartment followed by two phases of elimination. The half-life of the rapid elimination phase was 83.5 min and of the slower phase was 12 h. The term (Vss/Vc)-1was 12.3 indicating extensive distribution into the tissues. Triamcinolone acetonide given i.v. or intramuscularly (i.m. ) ind...
Gozalo-Marcilla M, Luna SPL, Gasthuys F, Schauvliege S.To perform a literature review of the thermal and mechanical antinociceptive devices used in pharmacological studies in standing horses published after 2011 (2012-2019). To complete a full literature review about electrical stimulation used for evaluation in similar studies. Methods: PubMed, Google Scholar and Web of Science. Conclusions: A high level of standardization has been reached in antinociceptive studies in standing horses using thermal and mechanical stimuli in most recent years. Commercially available testing devices to deliver thermal, mechanical and electrical stimuli, with observ...
Gretler SR, Finno CJ, Kass PH, Knych HK.In humans, the drug metabolizing enzyme CYP2D6 is highly polymorphic resulting in substantial differences in the metabolism of drugs including anti-arrhythmics, neuroleptics, and opioids. The objective of this study was to phenotype a population of 100 horses from five different breeds and assess differences in the metabolic activity of the equine CYP2D6 homolog using codeine as a probe drug. Administration of a probe drug is a common method used for patient phenotyping in human medicine, whereby the ratio of parent drug to metabolite (metabolic ratio, MR) can be used to compare relative enzym...
de Wasseige S, Picotte K, Lavoie JP.A study reported low systemic availability of injectable dexamethasone nebulized to healthy horses using the Flexineb mask. When used in horses with severe asthma and a different nebulizer, lack of efficacy and cortisol suppression were observed. Objective: Nebulized dexamethasone is as effective as PO administration for the treatment of severe asthma in horses. Methods: Twelve horses with severe asthma from a research herd. Methods: Randomized clinical trial. Horses were divided into 2 groups and received 5 mg of dexamethasone sodium phosphate by nebulization using a Flexineb mask (NE, n = 6)...
Blackford J, Doherty TJ, Ferslew KE, Panus PC.In human rehabilitation medicine, dexamethasone-phosphate is theoretically iontophoresed to localized subcutaneous tissue where conversion to dexamethasone occurs. This delivery system has recently been introduced into veterinary medicine for the same purpose. However, the pharmacokinetic justification for parenteral delivery of this prodrug remains undocumented. Utilizing iontophoretic methods that are relevant to both human and veterinary clinical practice, the present investigation compared injection and iontophoresis of dexamethasone-phosphate into the equine tibiotarsal joint, also known ...
Williams MM, Spiess BM, Pascoe PJ, O'Grady M.OBJECTIVE: To identify any systemic effects of topical and subconjunctival administration of atropine sulfate in the horse. Animals studied Six mature grade horses were treated hourly in one eye with topical ophthalmic atropine drops for 24 h. Five horses were treated subconjunctivally in one eye with 3 mg of atropine sulfate. Procedures Pupillary light reflexes, pupil size, electrocardiographic parameters, girth measurements, intestinal motility, and clinical signs of abdominal pain were monitored. RESULTS: Alteration in auscultated gut motility and clinical signs of abdominal pain were the m...
Peters LM, Demmel S, Pusch G, Buters JT, Thormann W, Zielinski J, Leeb T, Mevissen M, Schmitz A.Ketamine is an anesthetic and analgesic regularly used in veterinary patients. As ketamine is almost always administered in combination with other drugs, interactions between ketamine and other drugs bear the risk of either adverse effects or diminished efficacy. Since cytochrome P450 enzymes (CYPs) play a pivotal role in the phase I metabolism of the majority of all marketed drugs, drug-drug interactions often occur at the active site of these enzymes. CYPs have been thoroughly examined in humans and laboratory animals, but little is known about equine CYPs. The characterization of equine CYP...
Hunyadi L, Papich MG, Pusterla N.The purpose of this study was to determine the pharmacokinetics of the FDA-approved labeled dose of diclazuril and compare it to a low dose in plasma and CSF in adult horses. During each research period, six healthy adult horses received 0.5 mg/kg of 1.56% diclazuril pellets (Protazil(TM) , Merck Animal Health) compared to the approved labeled dose of 1 mg/kg orally once in two separate phases. A dose of 0.5 mg/kg was calculated to each horse's weight. Blood was then collected immediately before diclazuril administration and then at regular intervals up to a 168 h. After the last blood collect...
Thibault CJ, Wilson DV, Robertson SA, Sharma D, Kinsley MA.To determine time to first passage of feces, total fecal piles and incidence of colic in the first 24 hours postprocedure in horses undergoing standing sedation with detomidine, or general anesthesia with or without detomidine. Methods: Retrospective cohort study. Methods: A total of 246 horses. Methods: Records of all horses that underwent standing sedation or general anesthesia between December 2012 and March 2016 were reviewed. Horses aged <6 months, admitted for colic or cesarean section, with inadequate data, and those not administered xylazine and/or detomidine were excluded. Records inc...
Sellon DC, Papich MG, Palmer L, Remund B.A two-way cross-over study of the pharmacokinetics of butorphanol after intravenous and intramuscular administration at 0.08 mg/kg in six adult horses was performed. Heparinized venous blood samples were obtained prior to drug administration and at 10, 20, 30, 45, 60, 120, 180, 240, and 360 min after IV injection. Samples were obtained at the same time points and at 6 h and 12 h after IM injection. Physical examination parameters were recorded at each time point. Plasma butorphanol concentrations were determined by high performance liquid chromatography. No significant differences in any physi...
Ström L, Dalin F, Domberg M, Stenlund C, Bondesson U, Hedeland M, Toutain PL, Ekstrand C.Topical ophthalmic atropine sulfate is an important part of the treatment protocol in equine uveitis. Frequent administration of topical atropine may cause decreased intestinal motility and colic in horses due to systemic exposure. Atropine pharmacokinetics are unknown in horses and this knowledge gap could impede the use of atropine because of the presumed risk of unwanted effects. Additional information could therefore increase safety in atropine treatment. Results: Atropine sulfate (1 mg) was administered in two experiments: In part I, atropine sulfate was administered intravenously and t...
Corado CR, McKemie DS, Knych HK.OBJECTIVE To characterize polymorphisms of the gene for cytochrome P450 isozyme 2D50 (CYP2D50) and the disposition of 2 CYP2D50 probe drugs, dextromethorphan and debrisoquine, in horses. ANIMALS 23 healthy horses (22 Thoroughbreds and 1 Standardbred). PROCEDURES Single-nucleotide polymorphisms (SNPs) in CYP2D50 were identified. Disposition of dextromethorphan (2 mg/kg) and debrisoquine (0.2 mg/kg) were determined after oral (dextromethorphan) or nasogastric (debrisoquine) administration to the horses. Metabolic ratios of plasma dextromethorphan and total dextrorphan (dextrorphan plus dextrorph...
Bousquet-Mélou A, Schneider M, El Garch F, Broussou DC, Ferran AA, Lallemand EA, Triboulloy C, Damborg P, Toutain PL.Marbofloxacin (MBX), a fluoroquinolone (FQ), is considered as a critical antibiotic requiring antimicrobial susceptibility testing (AST) for prudent use. No clinical breakpoint (CBP) currently exists to interpret the results of such tests in horses. Objective: To compute PK/PD cut-offs (PK/PDCO ) that is one of the three minimum inhibitory concentrations (MICs) considered establishing a CBP for antimicrobial susceptibility test interpretation. Methods: A meta-analysis conducted by combining five sets of previously published pharmacokinetic data, obtained in clinical and nonclinical settings. M...
Olsen SC, Coyne CP, Lowe BS, Pelletier N, Raub EM, Erickson HH.Four hours prior to exercise on a high-speed treadmill, 4 dosages of furosemide (0.25, 0.50, 1.0, and 2.0 mg/kg of body weight) and a control treatment (10 ml of 0.9% NaCl) were administered IV to 6 horses. Carotid arterial pressure (CAP), pulmonary arterial pressure (PAP), and heart rate were not different in resting horses before and 4 hours after furosemide administration. Furosemide at dosage of 2 mg/kg reduced resting right atrial pressure (RAP) 4 hours after furosemide injection. During exercise, increases in treadmill speed were associated with increases in RAP, CAP, PAP, and heart rate...
Targowski SP.Treatment of ponies with a single dose of prednisolone markedly reduced the number of blood lymphocytes. A decrease of the number of eosinophils was also observed. In contrast, the number of neutrophils significantly increased. These profound changes were temporary and returned to the pretreatment level within 48 h. The number of monocytes did not show any of the significant changes post-prednisolone treatment. The reactivity of the blood lymphocytes of these ponies, in vitro, to stimulation with phytohemagglutinin (PHA) or streptokinase-strepto-dornase (SK-SD) was measured by incorporation of...
Paine SW, Bright J, Scarth JP, Hincks PR, Pearce CM, Hannan C, Machnik M, Hillyer L.In equine and racing practice, detomidine and butorphanol are commonly used in combination for their sedative properties. The aim of the study was to produce detection times to better inform European veterinary surgeons, so that both drugs can be used appropriately under regulatory rules. Three independent groups of 7, 8 and 6 horses, respectively, were given either a single intravenous administration of butorphanol (100 µg/kg), a single intravenous administration of detomidine (10 µg/kg) or a combination of both at 25 (butorphanol) and 10 (detomidine) µg/kg. Plasma and urine concentratio...
Mama KR, Pascoe PJ, Steffey EP, Kollias-Baker C.To characterize responses associated with two 1-hour total intravenous anesthesia techniques in horses. Methods: 6 mature, healthy mares. Methods: Each horse was anesthetized 3 times. Treatment order was determined by a series of Latin squares. After baseline measurements and instrumentation, horses were given xylazine (XYL) i.v.; anesthesia was induced 5 minutes later with 10% guaifenesin given i.v., then either ketamine (KET) or propofol (PRO) was given i.v. After anesthesia induction, each horse received an infusion of XYL and either KET or a low or high dose of PRO. Cardiopulmonary variabl...
