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.
Sykes BW, Underwood C, McGowan CM, Mills PC.The objectives of this study were to investigate the impact of formulation (enteric coated and buffered) and feeding on pharmacokinetic variables associated with the oral administration of omeprazole in the horse. Six thoroughbred racehorses were studied in a crossover design. Each received 2 g of an enteric coated or buffered formulation in both the fed and fasted state. Plasma omeprazole concentrations were determined by UHPLC-MS. The effects of feeding or formulation on AUC0-inf_obs, half-life, Tmax or Cmax were not statistically significant. However, a wider-than-expected degree of variati...
Underwood C, Collins SN, Mills PC, Van Eps AW, Allavena RE, Medina Torres CE, Pollitt CC.Pharmaceutical agents with potential for laminitis prevention have been identified. Many of these, including the MMP inhibitor marimastat, are impractical for systemic administration. This study compared local delivery of marimastat by regional limb perfusion (RLP) to systemic intravenous bolus dosing (SIVB), and established whether RLP results in local lamellar drug delivery. Six adult horses received 0.23 mg/kg of marimastat by RLP followed by 0.23 mg/kg marimastat by SIVB, with a 24-h washout period. Lamellar ultrafiltration probes sampled lamellar interstitial fluid as lamellar ultrafiltra...
Rendle DI, Hughes KJ, Doran GS, Edwards SH.To determine the pharmacokinetics of pergolide after IV administration to horses. Methods: 8 healthy adult horses. Methods: Pergolide mesylate was administered IV at a dose of 20 μg/kg (equivalent to 15.2 μg of pergolide/kg) to each horse, and blood samples were collected over 48 hours. Pergolide concentrations in plasma were determined by means of high-performance liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were determined on the basis of noncompartmental methods. Results: After IV administration of pergolide, mean ± SD clearance, elimination half-life, a...
Kim TW, Della Rocca G, Di Salvo A, Ryschanova R, Sgorbini M, Giorgi M.To determine the pharmacokinetics of cimicoxib and to assess the inhibition of cyclooxygenase (COX) after a 5 mg/kg, single oral administration in horses that were fasted or fed. Methods: The study was conducted using an open, single dose (5 mg/kg), two treatment (fasted and fed), two-period, crossover design with a 2-week interval between dosages. Six healthy mares received 5 mg/kg of cimicoxib via nasogastric tube after fasting for 12 hours, or 2 hours after feeding. After administration, blood samples were collected for up to 24 hours and plasma used for pharmacokinetic analysis. Addi...
Hines SA, Ramsay JD, Kappmeyer LS, Lau AO, Ojo KK, Van Voorhis WC, Knowles DP, Mealey RH.The apicomplexan hemoparasite Theileria equi is a causative agent of equine piroplasmosis, eradicated from the United States in 1988. However, recent outbreaks have sparked renewed interest in treatment options for infected horses. Imidocarb dipropionate is the current drug of choice, however variation in clinical response to therapy has been observed. Methods: We quantified the in vitro susceptibility of two T. equi isolates and a lab generated variant to both imidocarb dipropionate and a bumped kinase inhibitor compound 1294. We also evaluated the capacity of in vitro imidocarb dipropionate ...
Regan FH, Hockenhull J, Pritchard JC, Waterman-Pearson AE, Whay HR.To identify pain-related behaviour in working donkeys in order to assist their owners and veterinarians to recognise and manage pain. Objective: To identify general and specific behaviours associated with pain or its relief using a trial with the nonsteroidal anti-inflammatory drug meloxicam (Metacam). Methods: Observer-blinded, placebo-controlled trial. Methods: Forty adult male working donkeys with common clinical abnormalities were randomly assigned to receive either a single loading dose of meloxicam (1.2 mg/kg bwt per os; n = 20) or a placebo (30 mg honey/250 ml water per os; n = 20...
Knych HK, Arthur RM, McKemie DS, Chapman N.Flunixin meglumine is commonly used in horses for the treatment of musculoskeletal injuries. The current ARCI threshold recommendation is 20 ng/mL when administered at least 24 h prior to race time. In light of samples exceeding the regulatory threshold at 24 h postadministration, the primary goal of the study reported here was to update the pharmacokinetics of flunixin following intravenous administration, utilizing a highly sensitive liquid chromatography-mass spectrometry (LC-MS). An additional objective was to characterize the effects of flunixin on COX-1 and COX-2 inhibition when drug con...
Lefebvre D, Pirie RS, Handel IG, Tremaine WH, Hudson NP.There is a need for an improved understanding of equine post operative ileus (POI), in terms of both clinical definition and optimal management. Although the pharmacological strategies that are used to treat POI continue to evolve, little is known about the supplementary strategies used to prevent and manage this condition. Objective: To report the current strategies used to diagnose, prevent and manage POI following emergency abdominal surgeries. Methods: Cross-sectional survey. Methods: An electronic survey invitation was sent by email to 306 European college diplomates (European Colleges of...
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...
Carregaro AB, Freitas GC, Ribeiro MH, Xavier NV, Dória RG.Continuous-rate infusion (CRI) of drugs results in more stable plasma drug concentrations than administration of intermittent boluses, thus providing greater stability of physiological parameters. The aim of this study was to evaluate the physiologic and analgesic effects of the administration of morphine, butorphanol, tramadol or methadone by CRI in horses with induced synovitis of the radiocarpal joint. Results: Increased values of cardiorespiratory parameters and body temperature were observed in all groups after initiation of opioid administration, and these increases were sustained throug...
Cook VL, Blikslager AT.To review the physiology of the cyclooxygenase (COX) enzymes with reference to the beneficial effects of nonsteroidal anti-inflammatory drugs (NSAIDs) related to their analgesic and antiendotoxic properties as well as the mechanisms responsible for adverse gastrointestinal, renal, and coagulation effects. Methods: Human and veterinary peer reviewed literature Results: NSAIDs are frequently administered to critically ill horses for their analgesic and anti-inflammatory effects. However, NSAIDs have significant side effects principally on the gastrointestinal mucosa and kidneys. These side effec...
Chiavaccini L, Claude AK, Lee JH, Ross MK, Meyer RE, Langston VC.The study objective was to compare butorphanol pharmacokinetics and physiologic effects following intravenous and subcutaneous administration in horses. Ten adult horses received 0.1 mg/kg butorphanol by either intravenous or subcutaneous injections, in a randomized crossover design. Plasma concentrations of butorphanol were measured at predetermined time points using highly sensitive liquid chromatography-tandem mass spectrometry assay (LC-MS/MS). Demeanor and physiologic variables were recorded. Data were analyzed with multivariate mixed-effect model on ranks (P ≤ 0.05). For subcutaneous i...
Kramer CM, Tsang AS, Koenig T, Jeffcott LB, Dart CM, Dart AJ.To survey veterinary practitioners in Australia on how they administer pentosan polysulfate (PPS) to horses and their perceptions of the efficacy of PPS for: the prevention and treatment of osteoarthritis (OA), the treatment of OA when PPS is combined with other drugs, and the efficacy of PPS compared with other disease-modifying osteoarthritic drugs. Methods: Practitioners were contacted by email, which contained a link to an online survey. Results: A total of 76 responses (34.5%) to the survey were received. Respondents most commonly used PPS as prophylactic therapy prior to competition (80....
Wong DM, Davis JL, Alcott CJ, Hepworth-Warren KL, Galow-Kersh NL, Rice S, Coetzee JF.The objective of this study was to evaluate the pharmacokinetic properties and physiologic effects of a single oral dose of alprazolam in horses. Seven adult female horses received an oral administration of alprazolam at a dosage of 0.04 mg/kg body weight. Blood samples were collected at various time points and assayed for alprazolam and its metabolite, α-hydroxyalprazolam, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of alprazolam was analyzed by a one-compartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single-dose administration of ...
Umar MA, Fukui S, Kawase K, Itami T, Yamashita K.Cardiovascular effects of total intravenous anesthesia using ketamine-medetomidine-propofol drug combination (KMP-TIVA) were determined in 5 Thoroughbred horses undergoing surgery. The horses were anesthetized with intravenous administration (IV) of ketamine (2.5 mg/kg) and midazolam (0.04 mg/kg) following premedication with medetomidne (5 µg/kg, IV) and artificially ventilated. Surgical anesthesia was maintained by controlling propofol infusion rate (initially 0.20 mg/kg/min following an IV loading dose of 0.5 mg/kg) and constant rate infusions of ketamine (1 mg/kg/hr) and medetomidine (1.25...
Dembek KA, Hurcombe SD, Schober KE, Toribio RE.To describe a case of supraventricular tachycardia and sudden death in a horse following administration of flecainide acetate. Methods: An 8-year-old Hanoverian warmblood gelding was treated for chronic, naturally occurring, supraventricular tachycardia with digoxin, procainamide hydrochloride, quinidine sulfate, and flecainide acetate. After oral administration of flecainide, polymorphic ventricular tachycardia (torsades de pointes) and ventricular fibrillation developed, leading to cardiovascular collapse and death. Conclusions: Atrial fibrillation is the most commonly diagnosed dysrhythmia ...
Holland B, Fogle C, Blikslager AT, Curling A, Barlow BM, Schirmer J, Davis JL.The objectives of this study were to compare the pharmacokinetics and COX selectivity of three commercially available formulations of firocoxib in the horse. Six healthy adult horses were administered a single dose of 57 mg intravenous, oral paste or oral tablet firocoxib in a three-way, randomized, crossover design. Blood was collected at predetermined times for PGE2 and TXB2 concentrations, as well as plasma drug concentrations. Similar to other reports, firocoxib exhibited a long elimination half-life (31.07 ± 10.64 h), a large volume of distribution (1.81 ± 0.59L/kg), and a slow clearanc...
Robinson MA, Guan F, McDonnell S, Uboh CE, Soma LR.Dermorphin is a μ-opioid receptor-binding peptide that causes both central and peripheral effects following intravenous administration to rats, dogs, and humans and has been identified in postrace horse samples. Ten horses were intravenously and/or intramuscularly administered dermorphin (9.3 ± 1.0 μg/kg), and plasma concentration vs. time data were evaluated using compartmental and noncompartmental analyses. Data from intravenous administrations fit a 2-compartment model best with distribution and elimination half-lives (harmonic mean ± pseudo SD) of 0.09 ± 0.02 and 0.76 ± 0.22 h, respe...
Ekstrand C, Bondesson U, Gabrielsson J, Hedeland M, Kallings P, Olsén L, Ingvast-Larsson C.Detection times and screening limits (SL) are methods used to ensure that the performance of horses in equestrian sports is not altered by drugs. Drug concentration-response relationship and knowledge of concentration-time profiles in both plasma and urine are required. In this study, dexamethasone plasma and urine concentration-time profiles were investigated. Endogenous hydrocortisone plasma concentrations and their relationship to dexamethasone plasma concentrations were also explored. A single dose of dexamethasone-21-isonicotinate suspension (0.03 mg/kg) was administered intramuscularly t...
Claunch KM, Eggleston RB, Baxter GM.To compare the effects of 2 approaches and 2 injection volumes on diffusion of mepivacaine hydrochloride for local analgesia of the deep branch of the lateral plantar nerve (DBLPN) in horses. Methods: Experimental study. Methods: 16 adult horses. Methods: Either 2 mL (low volume) or 8 mL (high volume) of mepivacaine hydrochloride-iohexol (50:50 mixture) was injected by means of 1 of 2 techniques to produce analgesia of the DBLPN. For technique 1, the needle was inserted 15 mm distal to the head of the fourth metatarsal bone and directed perpendicular to the limb. For technique 2, the needle wa...
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 ...
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...
Knych HK, Arthur RM, Mitchell MM, Holser I, Poppenga R, Smith LL, Helm MN, Sams RA, Gaskill CL.Cobalt has been used by human athletes due to its purported performance-enhancing effects. It has been suggested that cobalt administration results in enhanced erythropoiesis, secondary to increased circulating erythropoietin (EPO) concentrations leading to improvements in athletic performance. Anecdotal reports of illicit administration of cobalt to horses for its suspected performance enhancing effects have led us to investigate the pharmacokinetics and pharmacodynamic effects of this compound when administered in horses, so as to better regulate its use. In the current study, 18 horses were...
Cagnardi P, Ferraresi C, Zonca A, Pecile A, Ravasio G, Zani DD, Villa R.Tramadol is a synthetic codeine analogue used as an analgesic in human and veterinary medicine. It is not approved for use in horses, but could represent a valid tool for pain treatment in this species. Objective: The serum pharmacokinetic profile and urinary excretion of tramadol and its metabolites (O-desmethyltramadol [M1], N-desmethyltramadol [M2] and N,O-desmethyltramadol [M5]) was investigated in a multidrug anaesthetic and analgesic approach for orchiectomy in horses. The evaluation of the degree of cardiovascular stability, the intraoperative effect and postoperative analgesia obtained...
Swain EA, Magdesian KG, Kass PH, Edman JE, Knych HK.Neonatal foals have unique pharmacokinetics, which may lead to accumulation of certain drugs when adult horse dosage regimens are used. Given its lipophilic nature and requirement for hepatic metabolism, metronidazole may be one of these drugs. The purpose of this study was to determine the pharmacokinetic profiles of metronidazole in twelve healthy foals at 1-2.5 days of age when administered as a single intravenous (IV) and intragastric (IG) dose of 15 mg/kg. Foals in the intravenous group were studied a second time at 10-12 days of age to evaluate the influence of age on pharmacokinetics wi...
Sykes BW, Underwood C, McGowan CM, Mills PC.The objectives were to document the pharmacokinetics of intravenous, enteric-coated oral and plain oral omeprazole in fasted horses and to investigate the impact of feeding on the bioavailability of an enteric-coated omeprazole. Twelve horses received four treatments: intravenous omeprazole (0.5 mg/kg) in the fasted state (IV-Fasted), enteric-coated omeprazole (4 mg/kg) orally in the fasted state (ECO-Fasted), enteric-coated omeprazole (4 mg/kg) orally in the fed state (ECO-Fed) and plain omeprazole (4 mg/kg) orally in the fasted state (PL-Fasted). Plasma omeprazole concentrations were det...
Knych HK, Steffey EP, Mitchell MM, Casbeer HC.The use of fentanyl is limited in adult horses, in part due to potential for central nervous system excitation. The pharmacokinetics and the plasma concentration-related behavioural actions of fentanyl have not been described for young foals. The goal of the present study was to describe the pharmacokinetics and behavioural effects of fentanyl following administration to the same group of foals at 3 different ages. Experimental study in healthy foals. Fentanyl was administered i.v. (4 μg/kg bwt) to a group of 9 foals on 3 separate occasions at 6–8, 20–22 and 41–42 days of age. Blood sam...
Kong N, Yi R, Zhao S, Sandhu J, Lam G, Loganathan D, Morrissey B.A sensitive hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry method was developed and validated for the simultaneous detection and quantification of etilefrine and oxilofrine in equine blood plasma and urine. The method is highly sensitive and specific with good precision and accuracy. In plasma the limit of detection and limit of quantification are 0.03 and 0.1 ng/mL, respectively, for both analytes. In urine the limit of detection and limit of quantification are 0.3 and 1 ng/mL, respectively, for both analytes. The suitability of the method for doping con...
Knych HK, Steffey EP, Casbeer HC, Mitchell MM.Foal responses to a broader range of plasma fentanyl concentrations than currently reported are desirable to support (or not) clinical use. Objective: To describe fentanyl plasma concentrations following an escalating i.v. fentanyl dosing schedule in foals aged 5-13 days and describe selected, associated dose- and time-related behavioural and physiological responses to plasma fentanyl concentration. Methods: Experimental. Methods: Fentanyl was administered i.v. in an escalating fashion (2, 4, 8, 16 and 32 μg/kg bwt) at 10-min intervals. Blood samples were collected before and at selected time...
Knych HK, Arthur RM, Stanley SD, McKemie DS.In order to ensure the welfare of performance horses and riders as well as the integrity of the sport, the use of both therapeutic and illegal agents in horse racing is tightly regulated. While Dehydroepiandrosterone (DHEA) is not specifically banned from administration to racehorses in the United States and no screening limit or threshold concentration exists, the metabolic conversion of DHEA to testosterone make its presence in nutritional supplements a regulatory concern. The recommended regulatory threshold for total testosterone in urine is 55 and 20 ng/mL for mares and geldings, respec...
Gokbulut C, Cirak VY, Senlik B, Yildirim F, McKellar QA.This study aimed to determine the plasma disposition and faecal excretion of netobimin (NTB) and its respective metabolites as well as the efficacy against strongyles in horses following oral administration. Netobimin (10mg/kg) was administered orally to 8 horses. Blood and faecal samples were collected from 1 to 120h post-treatment and analysed by high performance liquid chromatography (HPLC). Using a chiral phase-based HPLC, plasma disposition of ABZSO enantiomers produced was also determined. Faecal strongyle egg counts (EPG) were performed by a modified McMaster's technique before and afte...
Giguère S, Burton AJ, Berghaus LJ, Haspel AD.The objective of this study was to compare the pharmacokinetics of minocycline in foals vs. adult horses. Minocycline was administered to six healthy 6- to 9-week-old foals and six adult horses at a dose of 4 mg/kg intragastrically (IG) and 2 mg/kg intravenously (i.v.) in a cross-over design. Five additional oral doses were administered at 12-h intervals in foals. A microbiologic assay was used to measure minocycline concentration in plasma, urine, synovial fluid, and cerebrospinal fluid (CSF). Liquid chromatography-tandem mass spectrometry was used to measure minocycline concentrations in ...
Capponi L, Schmitz A, Thormann W, Theurillat R, Mevissen M.To investigate cytochrome P450 (CYP) enzymes involved in metabolism of racemic and S-ketamine in various species and to evaluate metabolic interactions of other analgesics with ketamine. Methods: Human, equine, and canine liver microsomes. Methods: An analgesic was concurrently incubated with luminogenic substrates specific for CYP 3A4 or CYP 2C9 and liver microsomes. The luminescence signal was detected and compared with the signal for negative control samples. Ketamine and norketamine enantiomers were determined by use of capillary electrophoresis. Results: A concentration-dependent decrease...
Karanth S, Pope C.The organophosphorus insecticide tetrachlorvinphos (TCVP) is commonly used as a feed-through larvicide in many livestock species, including cattle and horses. Cholinesterase (ChE) activity in blood (generally plasma or whole blood) is often employed to assess organophosphorus insecticide intoxication in animals as well as humans. In many species, including horse and man, plasma contains predominantly butyrylcholinesterase whereas red blood cells in all species express exclusively acetylcholinesterase. To evalulate the comparative interaction of TCVP with blood ChEs in different species, we com...
Gold JR, Grubb TL, Green S, Cox S, Villarino NF.In humans, gabapentin an analgesic, undergoes non-proportional pharmacokinetics which can alter efficacy. No information exists on the pharmacokinetics of dosages >20 mg/kg, escalating dosages or dose proportionality of gabapentin in horses. Objective: Gabapentin exposure in plasma would not increase proportionally relative to the dose in horses receiving dosages ≥20 mg/kg. To assess the plasma pharmacokinetics of gabapentin after nasogastric administration of gabapentin at dosages of 10 to 160 mg/kg in adult horses. Methods: Nine clinically healthy adult Arabian and Quarter Horses....
Steffey EP, Pascoe PJ.To quantitate the dose- and time-related magnitude of the anesthetic sparing effect of, and selected physiological responses to detomidine during isoflurane anesthesia in horses. Methods: Randomized cross-over study. Methods: Three, healthy, young adult horses weighing 485 ± 14 kg. Methods: Horses were anesthetized on two occasions to determine the minimum alveolar concentration (MAC) of isoflurane in O and then to measure the anesthetic sparing effect (time-related MAC reduction) following IV detomidine (0.03 and 0.06 mg kg). Selected common measures of cardiopulmonary function, blood glucos...
Jaussaud P, Guieu D, Bellon C, Barbier B, Lhopital MC, Sechet R, Courtot D, Toutain PL.The pharmacokinetics of tolfenamic acid were studied in five ponies after an intravenous (iv) administration (2 mg/kg bodyweight [bwt]) and in four horses after an oral administration (30 mg/kg bwt) of tolfenamic acid. The plasma levels were determined by high pressure liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). For the iv administration, a three-compartment model was used to represent the plasma concentration-time curve of the drug. The elimination half-life of the compound was 6.1 +/- 1.5 h, the total body clearance was 72.4 +/- 16.7 ml/kg bwt/h and the ste...
Erickson BK, Erickson HH, Coffman JR.Intravenous frusemide (1.0 mg/kg bwt) or phentolamine (0.33 mg/kg bwt) was given to 7 horses 1 h before exercise and their effects on pulmonary artery and aortic pressure changes during strenuous exercise were examined. Short-term near-maximal treadmill exercise (10 m/sec, 3 degrees incline) produced increases in heart rate, mean pulmonary artery pressure (PAP), mean aortic pressure (AP), and packed cell volume (PCV). Frusemide did not affect heart rate, PAP or PCV during exercise. Frusemide significantly decreased mean AP by 10 to 15 mmHg during exercise. Phentolamine produced an increase in ...
Sams RA, Ruoff WW.The pharmacokinetics and bioavailability of cefazolin given (IV, IM) to horses at the dosage of 11 mg/kg were investigated. The disposition of cefazolin given by IV route was characterized by a rapid disposition phase with a half-life of 5 to 10 minutes and a subsequent slower elimination phase with a half-life of 35 to 46 minutes. The total plasma clearance of cefazolin averaged 5.51 ml/min/kg and was due mainly to renal clearance (5.39 ml/min/kg) of unchanged drug. The volume of distribution at steady-state averaged 188 ml/kg. Plasma protein binding of cefazolin at a concentration of 10 micr...
Gerhards H.Low dose calcium heparin was administered subcutaneously at 12 hourly intervals to six healthy horses at an initial dose of 150 iu of heparin/kg bodyweight (bwt) and at a maintenance dose of 120 iu/kg bwt. All injections were given at 0900 and 2100 h. Blood samples for monitoring plasma heparin concentrations were obtained prior to, at 2 hourly intervals for 84 h (treatment period), and at Hours 24, 32, 48 and 96 of the control period. Blood samples for monitoring red blood cell (RBC) mass, plasma antithrombin III activity (AT III), activated partial thromboplastin time (APTT), and thrombin ti...
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.
Pellegrini-Masini A, Poppenga RH, Sweeney RW.An injectable preparation of flunixin meglumine was administered orally and intravenously at a dose of 1.1 mg/kg to six healthy adult horses in a cross-over design. Flunixin meglumine was detected in plasma within 15 min of administration and peak plasma concentrations were observed 45-60 min after oral administration. Mean bioavailability of the oral drug was 71.9 +/- 26.0%, with an absorption half-life of 0.76 h. The apparent elimination half-life after oral administration was 2.4 h. The injectable preparation of flunixin meglumine is suitable for oral administration to horses.
Ibarra-Rubio ME, Pena JC, Pedraza-Chaverri J.1. Serum angiotensin-converting enzyme activities were obtained from nine mammalian species: rat, mouse, horse, sheep, guinea pig, hamster, rabbit, dog and man. 2. Kinetic constants (Km and Vmax) using hippuryl-L-histidyl-L-leucine as substrate and inhibitory constants (I50 and Ki) for captopril were determined for the serum ACE of each species. 3. There were important differences in the kinetic and inhibitory constants (Kms went from 6.6 mM to 1.21 mM for hamster and guinea pig; I50 ranged from 2100 nM to 3 nM for mouse and sheep) as well as differences in enzyme activity of the different spe...
Firth EC, Klein WR, Nouws JF, Wensing T.Single doses of sodium ampicillin (10 mg/kg) and kanamycin sulfate (5 mg/kg) were administered intramuscularly (i.m.) separately, and then together, to five pony mares. The plasma antibiotic concentration-time curves were constructed. The pharmacokinetic parameters of the antibiotics given separately were not altered by concurrent administration. Four of the five pony mares were then given the i.m. kanamycin/ampicillin combination 4 h after acute synovitis and fever had been induced by injection of lipopolysaccharide into the left intercarpal joint. The plasma concentration-time curves and the...
Ellerbrock RE, Canisso IF, Roady PJ, Rothrock LT, Zhong L, Wilkins P, Dirikolu L, Lima FS, Honoroto J.In selective cases, enrofloxacin may be an alternative antibacterial agent to treat unresponsive infections in pregnant mares. Supratherapeutic doses of enrofloxacin are toxic to adult horses and also to newborn foals, however, it is unknown if enrofloxacin crosses the equine placenta or if it is toxic to the fetus. Objective: To assess the diffusion of enrofloxacin and its metabolite to fetal fluids and its effects on fetal cartilage when administered to pregnant mares. Methods: In vivo and terminal controlled experiment. Methods: Healthy mares at 260 days of gestation were allocated into thr...
Vatistas NJ, Snyder JR, Hildebrand SV, Harmon FA, Woliner MJ, Barry SJ, Nieto J, Henry P, Enos LR, Magliano D, Brown SA, Drake C.To determine the effects of the 21-aminosteroid, U-74389G, on reperfusion of the equine jejunum, using total (TVO) and partial (PVO) vascular occlusion during the ischemic period. Methods: TVO: 16 healthy horses were randomly allotted to 3 groups-4 horses received the vehicle alone, 6 horses received a low dosage (3 mg/kg o body weight), and 6 horses a high dosage (10 mg/kg) of U-7438G. PVO: 10 healthy horses were randomly allotted to 2 groups--5 horses received the vehicle alone, and 5 horses received the low dosage (3 mg/kg) of U-74389G. Methods: TVO was induced for 1 hour followed by 2 hour...
Fielding CL, Brumbaugh GW, Matthews NS, Peck KE, Roussel AJ.To determine the pharmacokinetics and clinical effects of a subanesthetic, continuous rate infusion of ketamine administered to healthy awake horses. Methods: 8 adult horses. Methods: Ketamine hydrochloride was administered to 2 horses, in a pilot study, at rates ranging from 0.4 to 1.6 mg/kg/h for 6 hours to determine an appropriate dose that did not cause adverse effects. Ketamine was then administered to 6 horses for a total of 12 hours (3 horses at 0.4 mg/kg/h for 6 hours followed by 0.8 mg/kg/h for 6 hours and 3 horses at 0.8 mg/kg/h for 6 hours followed by 0.4 mg/kg/h for 6 hours). Conce...
von Fellenberg RL, Jordan JC, Ludwig B, Rehm WF.Aditoprim, a broad spectrum antimicrobial agent acting as a reversible dihydrofolate reductase inhibitor, was intravenously injected into four 12 to 24-year old horses at a dosage of 5 mg/kg b. w. Blood samples were collected over a 48-hour period after drug injection, and the separated plasma samples were assayed for aditoprim by high performance liquid chromatography. The body temperature, heart rate, respiration rate, and behaviour were recorded during the experiment. The bilirubin and urea concentrations were also determined in several plasma samples, and liver function tests were carried ...
Flynn H, Cenani A, Brosnan RJ, DiMaio Knych HK, de Araujo Aguiar AJ.To determine the pharmacokinetics and pharmacodynamics of high-concentration formulation of buprenorphine (1.8 mg mL; Simbadol) following subcutaneous (SC) administration in horses. Methods: Prospective, randomized, crossover trial. Methods: A group of six healthy adult horses weighing 521-602 kg. Methods: On three occasions, Simbadol (0.005 mg kg; treatment S5), (0.0025 mg kg; treatment S2.5) or saline (treatment SAL) were administered SC at least 7 days apart in random order. Electrical nociceptive threshold (ENT) measured on the neck region, physiologic variables, locomotor activity, degree...
Green SL, Conlon PD, Mama K, Baird JD.The effects of hypoxia and azotaemia on the pharmacokinetics of amikacin were evaluated in 20 full-term neonatal critically ill foals which required 24-h supportive care, antibiotics and dextrose-supplemented polyionic fluids given intravenously, nasal insufflation with oxygen and nutritional supplementation. There was no association between sepsis score or survival and pharmacokinetic parameters. Concurrent hypoxia and azotaemia were associated with significantly decreased clearance and increased peak and trough serum concentrations of amikacin; however, peaks or troughs did not exceed toxic ...
Mainguy-Seers S, Bessonnat A, Picotte K, Lavoie JP.Inhaled corticosteroids are effective in the treatment of equine asthma. A recent study reported that nebulisation of injectable dexamethasone had low systemic bioavailability in healthy horses and could represent a cost-effective therapy for equine inflammatory lung diseases. Objective: To determine the effects of dexamethasone nebulisation on lung function in severe asthmatic horses. It was hypothesised that dexamethasone administered by nebulisation would be more effective than the same dose administered orally. Methods: Randomised blinded experimental study in severe asthmatic horses. Meth...
Hall LW, Taylor PM.One hundred anaesthetics were administered in a clinical trial to 95 equine patients, ranging in age from nine months to 19 years and in weight from 140 to 1270 kg, undergoing a variety of surgical procedures. Acepromazine maleate premedication (0.01 to 0.03 mg per kg intramuscularly) was given to seven animals, the remainder were not premedicated. Xylazine (1.1 mg per kg) was injected intravenously over a two minute period and after a pause of two minutes ketamine (2.2 mg per kg) was injected rapidly by the same route. For 30 procedures no other anaesthetic was given but in 59 cases anaesthes...
Welsh CE, Parkin TDH, Marshall JF.As antimicrobial resistant bacterial strains continue to emerge and spread in human and animal populations, understanding prescription practices is key in benchmarking current performance and setting goals. Antimicrobial prescription (AP) in companion veterinary species is widespread, but is neither monitored nor restricted in the USA and Canada. The veterinary use of certain antimicrobial classes is discouraged in some countries, in the hope of preserving efficacy for serious human infections. Objective: The aim of this study was to ascertain the rate of prescription of a number of 'reserved'...
Linardi RL, Stokes AM, Andrews FM.Methadone is an effective analgesic opioid that may have a place for the treatment of pain in horses. However, its absorption seems to be impaired by the presence of a transmembrane protein, P-glycoprotein, present in different tissues including the small intestine in other species. This study aims to determine the effect of the P-glycoprotein on methadone flux in the equine intestinal mucosa, as an indicator of in vivo drug absorption. Jejunum tissues from five horses were placed into the Ussing chambers and exposed to methadone solution in the presence or absence of Rhodamine 123 or verapami...
Skarda RT, Muir WW.To determine the analgesic, hemodynamic, and respiratory effects induced by caudal epidural administration of meperidine hydrochloride in mares. Methods: 7 healthy mares. Methods: Each mare received meperidine (5%; 0.8 mg/kg of body weight) or saline (0.9% NaCl) solution via caudal epidural injection on 2 occasions. At least 2 weeks elapsed between treatments. Degree of analgesia in response to noxious electrical, thermal, and skin and muscle prick stimuli was determined before and for 5 hours after treatment. In addition, cardiovascular and respiratory variables were measured and degree of se...
Caldwell FJ, Mueller PO, Lynn RC, Budsberg SC.To determine whether 1% diclofenac liposomal suspension (DLS) ointment would be absorbed transdermally and attenuate experimentally induced subcutaneous inflammation in horses. Methods: 7 healthy adult horses. Methods: Inflammation was produced by injecting 1% sterile carrageenan into subcutaneously implanted tissue cages 8 hours before (time -8) and at the time of application of test ointment. A crossover design was used. Horses received 1 of 2 treatments (topically administered control or DLS ointments) during 48 hours of carrageenan-induced subcutaneous inflammation. A single application of...
Ekstrand C, Bondesson U, Gabrielsson J, Hedeland M, Kallings P, Olsén L, Ingvast-Larsson C.Detection times and screening limits (SL) are methods used to ensure that the performance of horses in equestrian sports is not altered by drugs. Drug concentration-response relationship and knowledge of concentration-time profiles in both plasma and urine are required. In this study, dexamethasone plasma and urine concentration-time profiles were investigated. Endogenous hydrocortisone plasma concentrations and their relationship to dexamethasone plasma concentrations were also explored. A single dose of dexamethasone-21-isonicotinate suspension (0.03 mg/kg) was administered intramuscularly t...
Davis JL, Papich MG, Morton AJ, Gayle J, Blikslager AT, Campbell NB.The purpose of this study was to determine the pharmacokinetics of etodolac following oral and intravenous administration to six horses. Additionally, in vitro cyclooxygenase (COX) selectivity assays were performed using equine whole blood. Using a randomized two-way crossover design, horses were administered etodolac (20 mg/kg) orally or intravenously, with a minimum 3-week washout period. Plasma samples were collected after administration for analysis using high pressure liquid chromatography with ultraviolet detection. Following intravenous administration, etodolac had a mean plasma half-li...
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 ...
