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.
Wieder ME, Paine SW, Hincks PR, Pearce CM, Scarth J, Hillyer L.Salbutamol sulphate (Ventolin Evohaler) was administrated via the inhalation route to six horses at a dose of 0.5 mg every 4 h during the day for 2 days (total dose 4 mg). Urine and blood samples were taken up to 92 h postadministration. Hydrolyzed plasma and urine were extracted using solid phase extraction (SPE). A sensitive tandem mass spectrometric method was developed in this study, achieving a lower limit of quantification (LLOQ) for salbutamol of 10 pg/mL in plasma and urine. The parent drug was identified using UPLC-MS/MS. Most of the determined salbutamol plasma concentrations, post l...
Ranheim B, Risberg ÅI, Spadavecchia C, Landsem R, Haga HA.Dexmedetomidine, the most selective α2-adrenoceptor agonist in clinical use, is increasingly being used in both conscious and anaesthetized horses; however, the pharmacokinetics and sedative effects of this drug administered alone as an infusion are not previously described in horses. Seven horses received an infusion of 8 μg dexmedetomidine/kg/h for 150 min, venous blood samples were collected, and dexmedetomidine concentrations were assayed using liquid chromatography-mass spectrometry (LC/MS) and analyzed using noncompartmental pharmacokinetic analysis. Sedation was scored as the distance...
Risberg A, Spadavecchia C, Ranheim B, Krontveit R, Haga HA.Dexmedetomidine and lignocaine IV are used clinically to provide analgesia in horses. The aims of this study were to investigate the antinociceptive effects, plasma concentrations and sedative effects of 2, 4 and 6 µg/kg/h dexmedetomidine IV, with a bolus of 0.96 µg/kg preceding each continuous rate infusion (CRI), and 20, 40 and 60 µg/kg/min lignocaine IV, with a bolus of 550 µg/kg preceding each CRI, in 10 Swiss Warmblood horses. Electrically elicited nociceptive withdrawal reflexes were evaluated by deltoid muscle electromyography. Nociceptive threshold and tolerance were determ...
Lopez BS, Giguère S, Berghaus LJ, Mullins MA, Davis JL.The objectives of this study were to investigate the pharmacokinetics of danofloxacin and its metabolite N-desmethyldanofloxacin and to determine their concentrations in synovial fluid after administration by the intravenous, intramuscular or intragastric routes. Six adult mares received danofloxacin mesylate administered intravenously (i.v.) or intramuscularly (i.m.) at a dose of 5 mg/kg, or intragastrically (IG) at a dose of 7.5 mg/kg using a randomized Latin square design. Concentrations of danofloxacin and N-desmethyldanofloxacin were measured by UPLC-MS/MS. After i.v. administration, da...
Pyörälä S, Taponen J, Katila T.Use of antimicrobials for veterinary indications related to reproduction in cattle and horses is reviewed. Antimicrobial compounds are widely used to treat and prevent infections of reproductive organs. Total amounts of antimicrobials for such purposes, estimated by weight, are low compared with major uses in food animals. The most common reproduction-related indication in cattle is mastitis. The number of intramammary products available for treatment of mastitis in the European Union is high. Metritis and endometritis also require antimicrobial treatment of cattle and specific products for in...
Heffron B, Benoit M, Bishop J, Costello S, Hurt L, Simpson L, Taddei L, Kline K, Negrusz A.During prolonged strenuous exercise, racehorses can experience acidemia. To counteract this phenomenon, trainers can administer blood alkalizing agents that raise the plasma pH and total carbon dioxide (TCO2) concentration. In Illinois, the administrative threshold for TCO2 in plasma is 37.0 mmol/L. Because accuracy in the reported measurement of TCO2 must be ensured, uncertainty measurements are often issued alongside the reported concentrations. We report a validated method for measuring TCO2 levels in equine plasma using the Beckman UniCel DxC 600. A six-point calibration curve ranging from...
Fultz L, Giguère S, Berghaus LJ, Grover GS, Merritt DA.Administration of ceftiofur sodium via nebulisation has been recommended for the treatment of bronchopneumonia in horses, despite the lack of pharmacokinetic and safety data. Objective: To compare concentrations of desfuroylceftiofur acetamide (DCA) in plasma and pulmonary epithelial lining fluid (PELF) of foals after nebulisation or i.m. administration of ceftiofur sodium and to determine if nebulisation of ceftiofur sodium induces airway inflammation. Methods: Randomised experimental study. Methods: Six weanling foals received ceftiofur sodium (2.2 mg/kg bwt daily for 5 doses) by the i.m. ...
Duesterdieck-Zellmer KF, Moneta L, Ott JF, Larson MK, Gorman EM, Hunter B, Löhr CV, Payton ME, Morré JT, Maier CS.To determine effects of intraarticularly administered tiludronate on articular cartilage in vivo, eight healthy horses were injected once with tiludronate (low dose tiludronate [LDT] 0.017 mg, n = 4; high dose tiludronate [HDT] 50 mg, n = 4) into one middle carpal joint and with saline into the contralateral joint. Arthrocentesis of both middle carpal joints was performed pre-treatment, and 10 min, 24 h, 48 h, 7 and 14 days after treatment. Synovial nucleated cell counts and total solids, tiludronate, sulfated glycosaminoglycan (sGAG), chondroitin sulfate 846 epitope (CS-846, a measure of aggr...
The locomotor pattern alterations produced after the administration of a sublingual detomidine gel was measured by an accelerometric method in horses. Using a randomized two-way crossover design, all animals (n = 6) randomly received either detomidine gel or a placebo administered sublingually. A triaxial accelerometric device was used for gait assessment 15 minutes before (baseline) and every 10 minutes after each treatment for a period of 180 minutes. Eight different parameters were calculated, including speed, stride frequency, stride length, regularity, dorsoventral, propulsion, mediolater...
Burton AJ, Giguère S, Arnold RD.Although gentamicin is highly active against Rhodococcus equi in vitro, its clinical efficacy has been limited presumably due to poor cellular uptake. Encapsulation of drugs in liposomes enhances their cellular uptake. Objective: To compare the disposition of liposomal gentamicin (LG) and free gentamicin (FG) in the plasma, pulmonary epithelial lining fluid and bronchoalveolar cells of healthy foals after i.v. administration or by nebulisation, and to assess the tolerability of the drug after repeated i.v. dosing. Methods: Experimental study. Methods: Eight healthy foals received a single i.v....
Casoni D, Spadavecchia C, Adami C.Prevention and treatment of intraoperative hypoxemia in horses is difficult and both efficacy and safety of therapeutic maneuvers have to be taken into account. Inhaled salbutamol has been suggested as treatment of hypoxia in horses during general anesthesia, due to safety and ease of the technique. The present report describes the occurrence of clinically relevant unwanted cardiovascular effects (i.e. tachycardia and blood pressure modifications) in 5 horses undergoing general anesthesia in dorsal recumbency after salbutamol inhalation. Balanced anesthesia based on inhalation of isoflurane in...
Knych HK, Steinmetz SJ, McKemie DS.The anti-anxiety and calming effects following activation of the GABA receptor have been exploited in performance horses by administering products containing GABA. The primary goal of the study reported here was to describe endogenous concentrations of GABA in horses and the pharmacokinetics, selected pharmacodynamic effects, and CSF concentrations following administration of a GABA-containing product. The mean (±SD) endogenous GABA level was 36.4 ± 12.5 ng/mL (n = 147). Sixteen of these horses received a single intravenous and oral dose of GABA (1650 mg). Blood, urine, and cerebrospin...
Kelmer G, Tatz AJ, Famini S, Bdolah-Abram T, Soback S, Britzi M.Regional limb perfusion (RLP) significantly decreases morbidity and mortality associated with distal limb injuries in horses. There is an urgent need for finding additional effective antimicrobial drugs for use in RLP. In this study, we tested the pharmacokinetics (PK) of chloramphenicol in RLP. Eight horses participated in the study, which was approved by the University Animal Care and Use Committee. The cephalic and the saphenous veins were used to perfuse the limbs. Synovial samples were collected from the metacarpo/metatarsophalangeal (MCP/MTP) joint. The Friedman Test was applied for asse...
Grimsrud KN, Ait-Oudhia S, Durbin-Johnson BP, Rocke DM, Mama KR, Rezende ML, Stanley SD, Jusko WJ.The present study characterizes the pharmacokinetic (PK) and pharmacodynamic (PD) relationships of the α2-adrenergic receptor agonists detomidine (DET), medetomidine (MED) and dexmedetomidine (DEX) in parallel groups of horses from in vivo data after single bolus doses. Head height (HH), heart rate (HR), and blood glucose concentrations were measured over 6 h. Compartmental PK and minimal physiologically based PK (mPBPK) models were applied and incorporated into basic and extended indirect response models (IRM). Population PK/PD analysis was conducted using the Monolix software implementing t...
Rezende ML, Grimsrud KN, Stanley SD, Steffey EP, Mama KR.The aim of the study was to describe the pharmacokinetics and selected pharmacodynamics of intravenous dexmedetomidine in horses. Eight adult horses received 5 μg/kg dexmedetomidine IV. Blood samples were collected before and for 10 h after drug administration to determine dexmedetomidine plasma concentrations. Pharmacokinetic parameters were calculated using noncompartmental analysis. Data from one outlier were excluded from the statistical summary. Behavioral and physiological responses were recorded before and for 6 h after dexmedetomidine administration. Dexmedetomidine concentrations dec...
Santonastaso A, Hardy J, Cohen N, Fajt V.In certain situations, an alternate route for parenteral drug administration in horses may be useful. The intra-osseous (IO) route may provide a safe alternative to the intravenous (i.v.) route for administration of sedatives to horses when the i.v. route is inaccessible or undesirable. Six adult horses were administered xylazine i.v. or IO in a block-randomized crossover design. For the i.v. trial, both jugular veins were catheterized, and one was used for xylazine administration, while the other was used for blood collection. For the IO trial, one jugular vein was catheterized for blood coll...
Costa GL, Cristarella S, Quartuccio M, Interlandi C.To evaluate the anti-nociceptive and sedative effects of slow intravenous (IV) injection of tramadol, romifidine, or a combination of both drugs in ponies. Methods: Within-subject blinded. Methods: Twenty ponies (seven male, 13 female, weighing mean ± SD 268.0 ± 128 kg). Methods: On separate occasions, each pony received one of the following three treatments IV; romifidine 50 μg kg(-) (R) tramadol 3 mg kg(-1) given over 15 minutes (T) or tramadol 3 mg kg(-1) followed by romifidine 50 μg kg(-1) (RT). Physiologic parameters and caecal borborygmi (CB) were measured and sedation ...
Delekta PC, Dobry CJ, Sindac JA, Barraza SJ, Blakely PK, Xiang J, Kirchhoff PD, Keep RF, Irani DN, Larsen SD, Miller DJ.Neurotropic alphaviruses, including western, eastern, and Venezuelan equine encephalitis viruses, cause serious and potentially fatal central nervous system infections in humans for which no currently approved therapies exist. We previously identified a series of thieno[3,2-b]pyrrole derivatives as novel inhibitors of neurotropic alphavirus replication, using a cell-based phenotypic assay (W. Peng et al., J. Infect. Dis. 199:950-957, 2009, doi:http://dx.doi.org/10.1086/597275), and subsequently developed second- and third-generation indole-2-carboxamide derivatives with improved potency, solub...
Theurillat R, Larenza MP, Feige K, Bettschart-Wolfensberger R, Thormann W.Ketamine and norketamine are being transported across the blood brain barrier and are also entering from blood into cerebrospinal fluid (CSF). Enantioselective distributions of these compounds in brain and CSF have never been determined. The enantioselective CE based assay previously developed for equine plasma was adapted to the analysis of these compounds in equine brain via use of an acidic pre-extraction of interferences prior to liquid/liquid extraction at alkaline pH. CSF can be treated as plasma. With 100 mg of brain tissue and 0.5 mL of CSF or plasma, assay conditions for up to 30 nmol...
Elfenbein JR, Robertson SA, MacKay RJ, KuKanich B, Sanchez L.Prolonged drug infusions are used to treat horses with severe signs of pain, but can be associated with altered gastrointestinal transit. The purpose of this study was to determine the effects of prolonged constant rate infusions (CRI) of lidocaine (L), butorphanol (B), and ketamine (K) alone and in combination on gastrointestinal transit, behavior, and thermal nociceptive threshold in healthy horses. Methods: Eight healthy adult horses were used in a randomized, cross-over, blinded, prospective experimental trial. Interventions were saline, L, K, B, LK, LB, BK, and LBK as an intravenous CRI f...
Nannarone S, Cenani A, Gialletti R, Pepe M.To compare, in horses undergoing laparotomy for colic, the effects of administering or not administering a loading intravenous (IV) bolus of lidocaine prior to its constant rate infusion (CRI). Effects investigated during isoflurane anaesthesia were end-tidal isoflurane concentration (Fe'ISO), cardiovascular function, anaesthetic stability and the quality of recovery. Methods: Prospective, randomized clinical study. Methods: Thirty-six client-owned horses. Methods: Horses were assigned randomly to receive lidocaine as a CRI (50 μg kg(-1) minute(-1) ) either preceded (LB) or not preceded (L...
Stahl J, Kietzmann M.The effect of physical and chemical permeation enhancers on in vitro transdermal permeation of lidocaine was investigated in the horse.Therefore, the effect of six vehicles (phosphate-buffered saline (PBS), 50% ethanol, 50% propylene glycol, 50% isopropylalcohol, 50% isopropylalcohol/isopropylmyristate and 50% dimethylsulfoxide) was examined as well as the effect of microneedle pretreatment with different needle lengths on transdermal drug delivery of lidocaine.The skin was obtained from the thorax of six Warmblood horses and was stored up to two weeks at - 20°C. Franz-type diffusion cells we...
Gómez-Díez M, Muñoz A, Caballero JM, Riber C, Castejón F, Serrano-Rodríguez JM.Pharmacokinetic and pharmacodynamic of IV enalapril at 0.50 mg/kg, PO placebo and PO enalapril at three different doses (0.50, 1.00 and 2.00 mg/kg) were analyzed in 7 healthy horses. Serum concentrations of enalapril and enalaprilat were determined for pharmacokinetic analysis. Angiotensin-converting enzyme (ACE) activity, serum ureic nitrogen (SUN), creatinine and electrolytes were measured, and blood pressure was monitored for pharmacodynamic analysis. The elimination half-lives of enalapril and enalaprilat were 0.67 and 2.76 h respectively after IV enalapril. Enalapril concentrations ...
Sykes BW, Sykes KM, Hallowell GD.A previous study demonstrated that a dose effect between 1.6 and 4.0 mg/kg bwt of omeprazole per os s.i.d. is present in the treatment of equine gastric ulceration. In the same study, healing of glandular ulceration appeared inferior to healing of squamous ulceration. However, several limitations were recognised in that study and further investigation is warranted. Objective: To further investigate the presence of a dose relationship in the treatment of gastric ulceration under conditions that may favour omeprazole efficacy such as administration prior to exercise and after a brief fast, and...
Tappenbeck K, Hoppe S, Geburek F, Feige K, Huber K.By blocking the enteric nervous system (ENS) using tetrodotoxin (TTX), previous studies have documented the contractility-enhancing (CE) effects of lidocaine in equine intestinal smooth muscle (SM) at the level of SM cells and/or interstitial cells of Cajal (ICC). The present study examined the impact of ENS deactivation on CE lidocaine effects, and investigated the effects of lidocaine on ENS activity. TTX application did not affect the CE effects of lidocaine, indicating that these were not mediated by TTX-sensitive sodium channels. Application of TTX or ≥100 mg/L lidocaine reduced ENS a...
Gozalo-Marcilla M, Gasthuys F, Schauvliege S.To review the literature with regard to the use of different intravenous agents as supplements to inhalational anaesthesia in horses. These drugs include lidocaine, ketamine, opioids and α2 -agonists. The Part 1 of this review will focus in the use of lidocaine and ketamine. Methods: Pubmed & Web of Science. Search terms: horse, inhalant anaesthesia, balanced anaesthesia, partial intravenous anaesthesia, lidocaine, ketamine. Conclusions: Different drugs and their combinations can be administered systemically in anaesthetized horses, with the aim of reducing the amount of the volatile agen...
Underwood C, Collins SN, van Eps AW, Allavena RE, Medina-Torres CE, Pollitt CC.There are no experimentally validated pharmacological means of preventing laminitis; however, locally acting pharmaceutical agents with the potential to prevent laminitis have been identified. Demonstrating therapeutic drug concentrations in lamellar tissue is essential for evaluating the efficacy of these agents. The aim of this study was to develop an experimental technique for repeatedly sampling lamellar interstitial fluid. A technique for placing ultrafiltration probes was developed in vitro using 15 cadaver limbs. Subsequently, lamellar ultrafiltration probes were placed in one forelimb ...
Mangal D, Uboh CE, Soma LR, Liu Y.Glucocorticoids (corticosteroids) are widely used anti-inflammatory agents in veterinary medical practice. These drugs are considered doping agents because they mask pain and thus, increase injury potential in equine athletes. They exhibit anti-inflammatory property by binding to glucocorticoids receptor (GR) to control the transcription of pro- and anti-inflammatory cytokines and enzymes involved in the synthesis of bioactive eicosanoids. To evaluate the role of triamcinolone acetonide (TA) on concentrations of bioactive eicosanoids in equine plasma, TA (0.04 mg/kg) was intravenously administ...
Smith KM, Pucket JD, Gilmour MA.To describe a reproducible technique for intrastromal injection in the standing horse for treatment of corneal stromal abscessation. Methods: A retrospective clinical study addressing the history, treatment, and outcome of six equids (six eyes) that received intrastromal voriconazole injection. Methods: Equids having a deep stromal abscess suspected to be of fungal origin were administered intrastromal injection of 5% voriconazole solution under standing sedation in an effort to bring about enhanced resolution of clinical disease. Results: Intracorneal administration of 5% voriconazole solutio...
Munoz T, Leclere M, Jean D, Lavoie JP.The purpose of this study is to measure the effect of long-term administration of inhaled fluticasone proprionate on cortisol concentrations in heaves-affected horses. Eleven horses with heaves were treated with fluticasone at least once daily at dosages required to improve lung function or with antigen avoidance alone for 1 year. Morning serum cortisol was measured before and after 10, 30, 110, 190, 230, 280, and 320 days of treatment. Cortisol was also measured in the afternoon of day 330. Cortisol was significantly lower in the Fluticasone group on days 30, 110, and 190 when compared with t...
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...
Mangal D, Uboh CE, Soma LR.Oxidative metabolites of arachidonic acid (AA) are implicated in inflammation. Thus, we evaluated cycloxygenases (COXs) and lipoxygenases (LOs) mediated metabolism of AA to eicosanoids in equine plasma. Eicosanoids were extracted from plasma by two liquid-liquid extraction (LLE) steps; first was by chloroform/isopropanol and second by methyl-tert-butyl ether. For identification and quantification of 25 eicosanoids, a highly specific, selective and sensitive stable isotope dilution liquid chromatography (LC) multiple reaction monitoring (MRM) mass spectrometric (MS) method was developed. To avo...
Meucci V, Minunni M, Vanni M, Sgorbini M, Corazza M, Intorre L.Detection of nonsteroidal anti-inflammatory drugs (NSAIDs) in equine plasma is a significant analytical problem in veterinary anti-doping controls. Results: A new HPLC method coupled to selective extraction with molecularly imprinted polymers was developed for the simultaneous determination in equine plasma of the NSAIDs phenylbutazone, flunixin, oxyphenbutazone, ketoprofen and naproxen. The analytical performances of the method have been evaluated both in standard solutions and equine plasma samples. Recovery: Molecularly imprinted polymers solid-phase extraction for all NSAIDs was >94% with ...
Ellse L, Burden F, Wall R.Equine pediculosis is a significant health and welfare issue, particularly in elderly and chronically debilitated animals. Currently infestation is controlled predominantly using topically applied pyrethroid insecticides, allowing limited scope for the rotation of drugs and increasing the risk of selection for resistance. Here the insecticidal efficacies of two pyrethroid-based products against the louse Bovicola (Werneckiella) ocellatus collected from donkeys were examined in vitro. The products were cypermethrin (Deosect™, Pfizer Ltd., 5% (w/v) cypermethrin, cutaneous spray) and permethrin...
Schmitz A, Thormann W, Moessner L, Theurillat R, Helmja K, Mevissen M.Ketamine, an injectable anesthetic and analgesic consisting of a racemic mixture of S-and R-ketamine, is routinely used in veterinary and human medicine. Nevertheless, metabolism and pharmacokinetics of ketamine have not been characterized sufficiently in most animal species. An enantioselective CE assay for ketamine and its metabolites in microsomal preparations is described. Racemic ketamine was incubated with pooled microsomes from humans, horses and dogs over a 3 h time interval with frequent sample collection. CE data revealed that ketamine is metabolized enantioselectively to norketamine...
Rubio-Martínez L, López-Sanromán J, Cruz AM, Santos M, San Román F.To study the pharmacokinetics of vancomycin in plasma obtained from the medullary sinusoids of the proximal phalanx (P1) after intravenous (IV) and intraosseous (IO) regional limb perfusion (RLP). Methods: Experimental study. Methods: Twelve horses. Methods: IV and IO RLP were performed in 2 groups (n = 6) of horses. Vancomycin hydrochloride (300 mg in 60 mL 0.9% NaCl) was randomly infused in 1 front limb, with the contralateral limb as control (60 mL 0.9% NaCl). A hole was drilled in the lateral cortex of P1, and blood samples from the medullary sinusoids of P1 were collected before infusion,...
Liska DA, Akucewich LH, Marsella R, Maxwell LK, Barbara JE, Cole CA.To determine serum pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite in horses after administration of a single IV dose and after single and multiple oral doses. Methods: 8 healthy adult horses. Methods: A crossover study design was used with a washout period of 6 days between treatments. Treatments were IV administration of a single dose of pentoxifylline (8.5 mg/kg) and oral administration of generic sustained-release pentoxifylline (10 mg/kg, q 12 h, for 8 days). Blood samples were collected 0, 1, 3, 6, 12, 20, 30, and 45 minutes and 1, 2, 4, 6, 8, and 12 hours after IV a...
Vyniarska A, Ziółkowski H, Madej-Śmiechowska H, Jaroszewski JJ.The aim of this study was to compare the pharmacokinetics of ivermectin and its antiparasitic activity in two horse breeds. Eight Hutsul and 14 Toric horses were administered ivermectin orally at a dose of 0.2 mg/kg body weight. Blood samples were collected for 96 hr, and faecal samples were collected one day before and on days 14 and 21 after drug administration. Ivermectin concentrations in plasma samples were determined by high-performance liquid chromatography. Ivermectin concentration was significantly higher in Toric than in Hutsul horses 90 min after ivermectin administration and was...
Nannarone S, Cenani A, Gialletti R, Pepe M.To compare, in horses undergoing laparotomy for colic, the effects of administering or not administering a loading intravenous (IV) bolus of lidocaine prior to its constant rate infusion (CRI). Effects investigated during isoflurane anaesthesia were end-tidal isoflurane concentration (Fe'ISO), cardiovascular function, anaesthetic stability and the quality of recovery. Methods: Prospective, randomized clinical study. Methods: Thirty-six client-owned horses. Methods: Horses were assigned randomly to receive lidocaine as a CRI (50 μg kg(-1) minute(-1) ) either preceded (LB) or not preceded (L...
Soma LR, Behrend E, Rudy J, Sweeney RW.The disposition of flunixin meglumine administered IV at a dosage of 1.1 mg/kg was described by a 2-compartment model; the alpha and beta half-lives (t1/2) were 0.61 and 1.5 hours, respectively. When administered IV at a rate of 2.2 mg/kg, the disposition was best described by a 3-compartment model, and the alpha, beta, and lambda t1/2 were 0.16, 1.52, and 6.00 hours, respectively. The zero-time plasma concentrations after flunixin meglumine was administered at 1.1 and 2.2 mg/kg were 9.3 +/- 0.76 and 21.5 +/- 7.4 mg/L, respectively. The bioavailability after oral administration of 1.1 mg/kg wa...
Colas C, Garcia P, Popot MA, Bonnaire Y, Bouchonnet S.A method has been developed for the analysis and characterization in equine urine and plasma of iridoid glycosides: harpagide, harpagoside and 8-para-coumaroyl harpagide, which are the main active principles of Harpagophytum, a plant with antiinflammatory properties. The method involves liquid chromatography coupled with positive electrospray ionization mass spectrometry. The addition of sodium or lithium chloride instead of formic acid in the eluting solvent has been studied in order to enhance the signal and to modify the ion's internal energy. Fragmentation pathways and associated patterns ...
Boermans HJ, Johnstone I, Black WD, Murphy M.Six horses gavaged with a commercial brodifacoum (BDF)-containing bait (Talone) at a dosage of 0.125 mg of BDF/kg of body weight showed weight loss, severe hypocoagulability and hemogram alterations. Four of the horses became depressed and anorectic; one required vitamin K1 therapy. Increases in clotting times were observed at 24 h in the partial thromboplastin time (PTT) followed by the thrombotest (TBT) and one-stage prothrombin time (PT) at 48 h. Elevated mean PTT, PT and TBT were observed from days 4 to 8 (p less than 0.05) with levels returning to pretreatment levels by day 12. Maximum pr...
Haines GR, Brown MP, Gronwall RR, Merritt KA, Baltzley LK.Pharmacokinetics and distribution of orbifloxacin into body fluids and endometrium was studied in 6 mares after intragastric (IG) administration at a single dose rate of 7.5 mg/kg body weight. Orbifloxacin concentrations were serially measured in serum, synovial fluid, peritoneal fluid, urine, cerebrospinal fluid, and endometrial tissues over 24 hours. Minimum inhibitory concentrations of orbifloxacin were determined for 120 equine pathogens over an 11-month period. The mean peak serum concentration (Cmax) was 2.41+/-0.30 microg/mL at 1.5 hours after administration and decreased to 0.17+/-0.01...
Bermingham E, Davis JL, Whittem T.The goal of this editorial is to discuss best practice design, execution and reporting of a pharmacokinetic (PK) study in horses. Our target readers are clinicians who plan to perform this type of research, in a field, clinic or research setting but we also hope that this article might help readers of such work to appraise the articles and understand the quality of the studies. Our emphasis will be on appropriate study design and analytical method, drug and drug formulation choice and route of administration, animal choice, sample collection, storage and shipping, and reporting, rather than th...
Hanson RR.Suitable use of prophylactic antimicrobial drugs for wounds depends on the accurate selection of appropriate antibiotics, dosing regimen, and duration of use. Regional intravenous delivery and intraosseous infusion of antibiotics are pivotal to a successful outcome for deep-rooted infections, inadequately perfused tissue, and infected wounds containing biofilm. Antibiotic-impregnated polymethylmethacrylate beads are predominantly helpful for wounds that have a poor blood supply and for those containing surgical implants that must remain in place.
Sano H, Martin-Flores M, Santos LC, Cheetham J, Araos JD, Gleed RD.To evaluate the effect of epidural morphine on gastrointestinal (GI) motility in horses. Methods: Randomly ordered crossover design. Methods: Six healthy adult horses weighing 585± 48 kg (mean±SD). Methods: Horses were randomly assigned to receive either 0.2 mg kg(-1) morphine or an equal volume (0.04 mL kg(-1)) of saline epidurally (the first inter coccygeal space) with 2 weeks between treatments. The horses were stabled, fed a standardized diet and allowed water ad libitum throughout the duration of the study. Radiopaque spheres were administered by stomach tube. Xylazine 0.2 mg kg(-1) int...
Leclere M, Magdesian KG, Cole CA, Szabo NJ, Ruby RE, Rhodes DM, Edman J, Vale A, Wilson WD, Tell LA.Azithromycin is widely used in foals but has not been studied in adult horses. The goals of this study were to determine the pharmacokinetic profile and to make a preliminary assessment of the safety of azithromycin in adult horses. Azithromycin was administered intravenously (5 mg/kg) and intragastrically (10 mg/kg) to six healthy mares in a crossover design. Serial plasma samples, blood neutrophils, and pulmonary macrophages were collected for the measurement of azithromycin concentrations. Azithromycin was also administered orally (10 mg/kg) once a day for 5 days to five healthy mares for p...
Ivester KM, Adams SB, Moore GE, Van Sickle DC, Lescun TB.To determine synovial fluid gentamicin concentrations and evaluate adverse effects on the synovial membrane and articular cartilage of tarsocrural joints after implantation of a gentamicin-impregnated collagen sponge. Methods: 6 healthy adult mares. Methods: A purified bovine type I collagen sponge impregnated with 130 mg of gentamicin was implanted in the plantarolateral pouch of 1 tarsocrural joint of each horse, with the contralateral joint used as a sham-operated control joint. Gentamicin concentrations in synovial fluid and serum were determined for 120 hours after implantation by use of ...
Theurillat R, Knobloch M, Levionnois O, Larenza P, Mevissen M, Thormann W.A robust CE method for the simultaneous determination of the enantiomers of ketamine and norketamine in equine plasma is described. It is based upon liquid-liquid extraction of ketamine and norketamine at alkaline pH from 1 mL plasma followed by analysis of the reconstituted extract by CE in the presence of a pH 2.5 Tris-phosphate buffer containing 10 mg/mL highly sulfated beta-CD as chiral selector. Enantiomer plasma levels between 0.04 and 2.5 microg/mL are shown to provide linear calibration graphs. Intraday and interday precisions evaluated from peak area ratios (n = 5) at the lowest calib...
Kamerling SG, Dequick DJ, Weckman TJ, Tobin T.Sensitive methods for measuring the analgesic, physiological and behavioural effects of opioids in the horse have recently been developed. Fentanyl, a prototypic mu-opiate receptor agonist, has been previously shown to produce a syndrome characterized by marked analgesia and locomotor stimulation as well as tachycardia, tachypnoea and behavioural arousal. To determine whether other opiate receptors mediate some of the actions of the narcotic analgesics in the horse, an agent with activity at kappa- and to lesser extent mu-receptors was studied using a vigorous experimental protocol. Like fenta...
Schneiders FI, Noble GK, Boston RC, Dunstan AJ, Sillence MN, McKinney AR.Acepromazine (ACP) is a useful therapeutic drug, but is a prohibited substance in competition horses. The illicit use of ACP is difficult to detect due to its rapid metabolism, so this study investigated the ACP metabolite 2-(1-hydroxyethyl)promazine sulphoxide (HEPS) as a potential forensic marker. Acepromazine maleate, equivalent to 30mg of ACP, was given IV to 12 racing-bred geldings. Blood and urine were collected for 7days post-administration and analysed for ACP and HEPS by liquid chromatography-mass spectrometry (LC-MS). Acepromazine was quantifiable in plasma for up to 3h with little r...
Harvey A, Kilcoyne I, Byrne BA, Nieto J.To compare synovial concentrations of amikacin following intravenous regional limb perfusion (IVRLP) with two different doses, and to compare their ability to reach target concentrations for bacterial isolates from common orthopedic conditions. Methods: Randomized crossover experiment. Methods: Six adult horses. Methods: Horses received IVRLP with 2 and 3 g of amikacin in the cephalic vein of alternate limbs (20 minutes tourniquet application and ≥14 days washout period). Amikacin concentrations were quantified in synovial fluid collected from the middle carpal and metacarpophalangeal joints...
Beretta C, Fadini L, Stracciari JM, Montesissa C.Febantel and one of its main metabolites, febantel sulphoxide, are chemically modified to only a slight extent when incubated in vitro with sheep and cattle ruminal fluids; other major metabolites, fenbendazole and oxfendazole, are respectively, oxidized to oxfendazole and reduced to fenbendazole. Febantel is negligibly metabolized by hepatic cytosol fractions but microsome preparations effect more extensive metabolic transformations. Important differences in this respect were found between microsome preparations from rat, horse, pig, cattle, sheep, chicken and trout livers.
Horspool LJ, McKellar QA.The present study was designed to determine and compare the plasma disposition and pharmacokinetics of penicillin G sodium following intravenous (i.v.) administration to horses, ponies and donkeys. The plasma disposition and pharmacokinetics of penicillin G was similar in horses, ponies and donkeys (elimination half-lives--39.0, 27.3 and 31.5 min, respectively) and a dosage interval of 6-8 h would be suitable to treat infections caused by susceptible bacteria. Although penicillin G was absorbed rapidly following nasogastric administration, the systemic availability was low (0.12-0.34%), theref...
Lees P, Taylor JB, Higgins AJ, Sedgwick AD.In vitro and in vivo studies of phenylbutazone binding to equine ingesta and digesta were undertaken. In vitro binding to chopped hay and powdered pony nuts in buffer solutions at 37 degrees C was found to be time-, concentration- and pH-dependent. Percentage binding generally increased with time, decreased with concentration and varied with buffer pH in an unpredictable manner. Other non-steroidal anti-inflammatory drugs (NSAIDs) also bound to hay, the degree of binding being less for meclofenamate and least for flunixin in comparison with phenylbutazone. Phenylbutazone became bound to digest...
Knych HK, Steffey EP, Mama KR, Stanley SD.To verify the isoflurane anesthetic minimum alveolar concentration (MAC)-sparing effect of a previously administered target plasma fentanyl concentration of 16 ng/mL and characterize an anticipated further sparing in isoflurane MAC associated with higher target plasma fentanyl concentrations. Methods: 8 horses. Methods: Horses were assigned 2 of 3 target plasma fentanyl concentrations (16, 24, and 32 ng/mL), administered in ascending order. Following determination of baseline MAC, horses received a loading dose of fentanyl followed by a constant rate infusion; MAC determination was performed i...
Di Salvo A, Giorgi M, Nannarone S, Lee HK, Corsalini J, Della Rocca G.NSAIDs are often used in horses with colic syndrome during the postoperative period, due to their ability to contrast endotoxemia and to promote an analgesic and anti-inflammatory effect. As the pharmacokinetics of a drug are often modified in unhealthy animals compared to healthy subjects, the aim of this study was to evaluate the pharmacokinetic profile of meloxicam after i.v. administration in horses undergoing laparotomy for colic syndrome. Eight horses received 0.6 mg/kg of meloxicam i.v. towards the end of surgery. Blood samples were taken at scheduled time points during the following 2...
Colas C, Garcia P, Popot MA, Bonnaire Y, Bouchonnet S.Solid-phase extraction cartridges among those usually used for screening in horse doping analyses are tested to optimize the extraction of harpagoside (HS), harpagide (HG), and 8-para-coumaroyl harpagide (8PCHG) from plasma and urine. Extracts are analyzed by liquid chromatography coupled with multi-step tandem mass spectrometry. The extraction process retained for plasma applies BondElut PPL cartridges and provides extraction recoveries between 91% and 93%, with RSD values between 8 and 13% at 0.5 ng/mL. Two different procedures are needed to extract analytes from urine. HS and 8PCHG are extr...
