The topic of drugs and horses encompasses the study of various pharmacological agents used in equine medicine for therapeutic purposes. This includes the administration of medications for pain management, disease treatment, and performance enhancement. The pharmacokinetics and pharmacodynamics of drugs in horses are key areas of research, as they determine the absorption, distribution, metabolism, and excretion of these substances. Additionally, the topic covers the detection and regulation of substances in competitive equestrian sports to ensure fair play and animal welfare. This page compiles peer-reviewed research studies and scholarly articles that explore the effects, safety, and regulatory aspects of drug use in equine health and performance.
Mills PC, Ng JC, Auer DE.The effect of inflammation on the disposition of phenylbutazone (PBZ) was investigated in Thoroughbred horses. An initial study (n = 5) in which PBZ (8.8 mg/kg) was injected intravenously twice, 5 weeks apart, suggested that the administration of PBZ would not affect the plasma kinetics of a subsequent dose. Two other groups of horses were given PBZ at either 8.8 mg/kg (n = 5) or 4.4 mg/kg (n = 4). Soft tissue inflammation was then induced by the injection of Freud's adjuvant and the administration of PBZ was repeated at a dose level equivalent to, but five weeks later than, the initial dose. ...
Klaus AM, Hapke HJ.This review compromises data about endogenous cortisol and its physiological variations in horses. The influence of synthetic glucocorticoids on the endogenous cortisol concentrations is discussed as well. The second part of the review summarizes detection times of therapeutically used glucocorticoids (dexamethasone, betamethasone, triamcinolone, prednisone, prednisolone, methylprednisolone and hydrocortisone) in the horse and their implication for doping control.
Landoni MF, Lees P.Pharmacokinetic and pharmacodynamic parameters were established for enantiomers of the non-steroidal anti-inflammatory drug (NSAID) ketoprofen (KTP), each administered separately at a dose level of 1.1 mg/kg to a group of six New Forest geldings, in a three-period cross-over study using a tissue cage model of inflammation. For both S(+)-and R(-)-KTP, penetration into tissue cage fluid (transudate) and inflamed tissue cage fluid (exudate) was rapid, and clearances from exudate and transudate were much slower than from plasma. AUC values were, therefore, higher for exudate and, to a lesser degre...
Singh S, McDonell WN, Young SS, Dyson DH.To assess the usefulness of glycopyrrolate (GLY) in preventing the decrease in cardiac index (CI) usually caused by xylazine (XYL)/ketamine (KET)-induced anesthesia in horses. Methods: 6 healthy horses. Methods: Horses were treated with saline solution or 2.5 micrograms of GLY/kg of body weight, administered i.v. 15 minutes later, XYL (1 mg/kg) was administered i.v., followed 5 minutes later by KET (2 mg/kg) administration. The horses were positioned in left lateral recumbency, insufflated with 15 L of oxygen/min, and maintained for 30 minutes on the infusion of 0.05 mg of XYL and 0.1 mg of KE...
Crisman MV, Wilcke JR, Sams RA.To determine pharmacokinetic variables that describe the disposition of flunixin after i.v. administration of flunixin meglumine to foals < 24 hours old. Methods: 6 healthy foals, 2 males and 4 females (mean age, 11.6 hours; range, 6 to 22.5 hours). Methods: Flunixin (as flunixin meglumine) was administered to foals at a dosage of 1.1 mg/kg of body weight. Flunixin concentration in plasma samples was analyzed, using gas chromatography/mass spectroscopy. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by j...
Ringger NC, Lester GD, Neuwirth L, Merritt AM, Vetro T, Harrison J.To investigate the prokinetic effect of bethanechol and erythromycin in the upper gastrointestinal tract of healthy horses by measuring the gastric emptying (GE) rate of a radioactive meal. Methods: 4 healthy adult horses. Methods: After food was withheld for 12 hours, horses were given 370 MBq of 99mTc-labeled sulfur colloid incorporated into egg albumen and 37 MBq of 111In-labeled diethyltriaminepentaacetic acid in 120 ml of water via nasogastric intubation. Intravenously administered treatments were 0.9% NaCl solution, erythromycin (0.1 or 1.0 mg/kg of body weight), or bethanechol (0.25 mg/...
Whittem T, Firth EC, Hodge H, Turner K.This study examined the pharmacokinetics of steady-state phenylbutazone and single bolus intravenous gentamicin when administered together in the horse. The trial design was completed as a cross-over with seven thoroughbred horses. In the first phase each horse received 2.2 mg/kg gentamicin intravenously. After a 2-week washout, each horse received 4.4 mg/kg phenylbutazone intravenously every 24 h for 5 days. On the fourth day each horse received gentamicin as before. Plasma was harvested for gentamicin concentration determination by fluorescence polarization immunoassay and for phenylbutazone...
Chapman MR, French DD, Monahan CM, Klei TR.Three fecal egg count reduction assays (FECR) and one critical trial were performed to determine the efficacy of pyrantel pamoate (PP) at 6.6 mg base kg-1 on a well managed stud farm in Louisiana where a loss of efficacy was suspected. Efficacy of PP based on FECR varied from 25% in mares to 83% in yearlings. Second treatments with PP 2 weeks following an initial treatment failed to reduce eggs per gram (EPG). A critical trial was performed to determine the cyathostome species resistant to PP. Three strongyle-naive ponies which acquired infections on the farm were used for this purpose. Follow...
Sysel AM, Pleasant RS, Jacobson JD, Moll HD, Modransky PD, Warnick LD, Sponenberg DP, Eyre P.Amphotericin B-induced synovitis of the left tarsocrural joint was used to create a grade 3 of 4 lameness in 11 horses. Caudal epidural catheters were placed and advanced to the lumbosacral region. Baseline heart and respiratory rates were recorded and horses were videotaped at a walk and trot. Morphine sulphate (0.2 mg/kg) and detomidine hydrochloride (30 micrograms/kg) were administered to treated horses (n = 8) through the epidural catheter; an equivalent volume of physiologic saline solution was administered to control horses (n = 3) through the catheter. At hourly intervals after epidural...
Ringger NC, Pearson EG, Gronwall R, Kohlepp SJ.Five healthy Equidae (4 horses and one pony) were given a single i.v. dose of ceftriaxone (50 mg/kg bwt) to determine the pharmacokinetics and concentration in cerebrospinal fluid (CSF). Blood was drawn from an i.v. jugular catheter and CSF from a pre-placed, intrathecal catheter. Serum and CSF concentrations were determined by high performance liquid chromatography. The mean serum concentration of ceftriaxone was 144.7 micrograms/ml 15 min after injection and declined to 0.3 microgram/ml 10 h after injection. The elimination rate constant (lambda 2) was 0.63 +/- s.e. 0.23/h, the elimination h...
Lyons ET, Tolliver SC, Drudge JH, Stamper S, Swerczek TW, Granstrom DE.Several compounds (n = 13 single or combinations; most at therapeutic dosages) were evaluated between 1977 and 1992 in critical tests (n = 91) against benzimidazole (BZ) resistant small strongyles (Population S) and several other species of internal parasites in Shetland ponies, mostly under 1 year old. The closed breeding herd, from which the test ponies were selected, had been treated every 8 weeks with cambendazole (CBZ) for 4 years (1974-1978) and oxibendazole (OBZ) for 14 years (1978-1992). Published field test data (1974-1992) on older ponies in the herd showed BZ resistance of small str...
Lyons ET, Tolliver SC, Drudge JH, Stamper S, Swerczek TW, Granstrom DE.Critical tests (91) were done between 1977 and 1992 in Shetland ponies to evaluate drug susceptibility and population dynamics (present paper) of endoparasites. The test ponies, most less than 1 year old, were from a herd where older animals were treated every 8 weeks initially with cambendazole (CBZ) (1974-1978) and then with oxibendazole (OBZ) (1978-1992). Previous field test data (1974-1992) on older ponies in the breeding herd indicated the presence of benzimidazole (BZ) resistant small strongyles. Data on population dynamics from the present critical tests indicated that 28 species of sma...
Black SB, Stenhouse AM, Hansson RC.This paper details various rapid and sensitive methods for the extraction and derivatisation of propranolol, metoprolol, sotalol, atenolol, pindolol, timolol, oxprenolol, alprenolol and penbutolol in equine urine and in human post mortem whole blood and urine. Three solid-phase extraction methods are described involving the use of either XtrackT XRDAH515, Bond Elut Certify or Sep-Pak C18 cartridges. Two derivatisation methods are also described involving the formation of cyclised silyl or pentafluoropropionate derivatives with either chloromethyldimethylchlorosilane or pentafluoropropionic anh...
Yamashita K, Yonezawa K, Izumisawa Y, Kotani T.The antagonistic effects of atipamezole (20, 40, 60, 80, and 100 micrograms/kg i.v.) on medetomidine (10 micrograms/kg i.v.)-induced sedation were evaluated in horses. Although 20 and 40 micrograms/kg of atipamezole were not sufficient to reverse the sedation, 60 micrograms/kg did effectively reverse the sedation. Atipamezole at 80 micrograms/kg was more potent, and significantly shortened the duration of sedation without any apparent side effects, but a higher dose of 100 micrograms/kg was not more effective than 80 micrograms/kg. The possible use of atipamezole as a reversal agent may enhanc...
Corveleyn S, Deprez P, Van der Weken G, Baeyens W, Remon JP.Six healthy mares ranging in age from 6 to 12 years and weighing from 415 to 540 kg were used to determine the rectal bioavailability of ketoprofen. For the rectal administration, three different formulations, each containing 1 g of ketoprofen, were administered in a fatty and a hydrophilic suppository base and as a liquid suspension. An average elimination half-life of 1.3 h (+/-1.2) was found. The average value for the total plasma clearance (ClT) was 131.9mL/ min.kg (range 95-183.5). The volume of distribution Vd(area) was 255 mL/kg and the mean residence time (MRT) value was 0.47 h. After ...
Aramaki S, Ishidaka O, Suzuki E, Momose A, Umemura K.In a doping test for racing horses, it is useful for the elucidation of the illegal use of drugs if one can estimate the time at which the detected drug was administered. In order to estimate the time which has elapsed after the administration of caffeine (CA) into horses, the ratios of concentration for the respective metabolites to the unchanged CA in the plasma or the urine were determined. These ratios have been known to be independent of the dose of CA. The relationship between [plasma or urinary concentration of a metabolite]/ [plasma or urinary concentration of the unchanged drug] and t...
Csik-Salmon J, Blais D, Vaillancourt D, Garon O, Bisaillon A.Loss of rear motor control is the main limiting factor in the use of caudal epidural anesthesia in the horse. In man and laboratory animals, a small dose of an opiate combined with a local anesthetic enhances analgesia without impairing motor function. Thus, the amount of local anesthetic administered may be reduced. Butorphanol is an opiate widely used in horses. It has a good margin of safety and few cardiorespiratory effects. The effects of lidocaine (0.25 mg/kg) and lidocaine-butorphanol (0.25 mg/kg, and 0.04 mg/kg, respectively) were compared in 2 groups of 5 healthy unsedated mares. Hors...
Taylor MR, Westwood SA, Perrett D.Micellar electrokinetic capillary chromatography (MECC) using diode array detection has been investigated for the determination of phase I and phase II metabolites of drugs in biofluids. Methods were optimised for the determination of morphine, morphine-3-glucuronide, morphine-6-glucuronide, normorphine, meclofenamic acid and its metabolites in equine urine. Solid-phase extraction procedure were developed to concentrate and purify the analytes from spiked and post administration urines for MECC analysis. A simple on-line procedure for monitoring the kinetics of hydrolysis of morphine-glucuroni...
Oukessou M, Bouljihad M, Van Gool F, Alvinerie M.The pharmacokinetic parameters of ketoprofen were determined in four donkeys after a single intravenous injection of a dose of 2.2 mg/kg body weight. The total body clearance (ClB) was 414.0 +/- 98.70 ml/h/kg (mean +/- SD), the volume of distribution at steady state (Vss) 263.10 +/- 55.43 ml/kg and the elimination half-life 1.30 +/- 0.75 h. These values were compared to those obtained in horses.
Manohar M, Goetz TE, Griffin R, Sullivan E.To determine the effects of phenylbutazone administration on heart rate and right atrial and pulmonary vascular pressures in Thoroughbreds during rest and during exercise performed at maximal heart rate. Methods: 7 healthy, exercise-conditioned Thoroughbreds. Methods: Horses were studied on 3 occasions: without medication [control], after i.v. administration of phenylbutazone (4.4 mg/kg of body weight) at 12-hour intervals for 2 days and a final dose given 1 hour before exercise, and after i.v. administration of phenylbutazone for 2 days in the same manner, but with the final dose given 24 hou...
Klee S, Nürnberger MC, Keller H, Ungemach FR.A therapeutical dose of kanamycin was tested intravenously and intramuscularly in four normal standardbreds and plasma concentrations were measured over a 12 hour period. Plasma levels exceeded a minimum inhibitory concentration of 4 micrograms/ml within only 15 minutes for 8 hours both after i.v. and i.m. injection. Kanamycin revealed a mean plasma half life of 2.3 hours. Bioavailability of an intramuscular dose was about 76%. The pharmacokinetic parameters demonstrate the rapid onset of antibacterial plasma levels of the test compound. A dose regimen for horses of two times daily 5 mg/kg bod...
Daugschies A.Drug resistance of parasites is a worldwide problem of increasing importance in animal production. Considerable information is available on the development of resistance in chicken coccidia and in strongyles of horses, sheep, goats and pigs. A review is given of the development, incidence, and management of drug resistance with emphasis on the situation in Germany.
Derksen FJ, Olszewski M, Robinson NE, Berney C, Lloyd JW, Hakala J, Matson C, Ruth D.Aerosol administration of bronchodilators to horses is recommended for treatment of certain airway diseases such as 'heaves'. We have developed a novel, hand-held, metered-dose inhaler and we sought to determine the bronchodilator efficacy of the beta 2 adrenoceptor agonist pirbuterol delivered by this device to horses affected with 'heaves'. To induce airway obstruction, 6 heaves-susceptible horses were stabled, bedded on straw and fed hay. When the maximum change in pleural pressure during tidal breathing (delta Pplmax) was greater than 20 cmH2O on 2 consecutive days, pulmonary function was ...
Delbeke FT.Urinary concentrations of the beta-antagonist oxprenolol and some of its major human metabolites were determined following oral administration of a dose of 160 mg to five fasted horses. Quantitation was performed by gas chromatography-mass spectrometry (GC-MS) in the selected ion mode (SIM) by monitoring ion m/z 466 of the heptafluorobutyric derivatives. As early as 2 h after dosage oxprenolol could be detected in hydrolysed urine and remained detectable up to 24 h. Maximum urinary concentrations and excretion rates were obtained between 2 and 12 h. After 12 h only 2.8% of the administered dos...
Ensink JM, Vulto AG, van Miert AS, Tukker JJ, Winkel MB, Fluitman MA.To determine the oral bioavailabilities of 3 ampicillin esters (pivampicillin, bacampicillin, and talampicillin) and ampicillin sodium, and to determine in vitro stability of the ampicillin esters in ileal contents (pH 8.3 to 8.5). Methods: A crossover design to administer the 4 drugs orally, and ampicillin i.v. to all horses in the study. Methods: 4 healthy adult horses. Methods: The drugs were administered intragastrically to the horses at a dosage equimolar to 15 mg of ampicillin/kg of body weight. Also, ampicillin sodium was administered i.v. at the same dosage. Blood samples were taken up...
Schutzer WE, Kerby JL, Holtan DW.Trilostane, a competitive inhibitor of 3 beta-hydroxysteroid dehydrogenase, was administered intravenously to pregnant mares (n = 3) between day 277 and day 282 of gestation to determine its effect on the progestin milieu. In addition, placental tissue from mares at mid-gestation (150-300 days) (n = 4) were exposed to either deuterium-labelled pregnenolone alone or deuterium-labelled pregnenolone and trilostane to examine the effect of trilostane on placental metabolism of pregnenolone. Blood samples were collected from indwelling jugular catheters at frequent intervals for 48 h after infusion...
Giguère S, Sweeney RW, Bélanger M.To investigate the pharmacokinetics of enrofloxacin in adult horses. Methods: 2-dose oral and i.v. cross-over trial followed by multiple oral doses. Methods: 8 clinically normal adult horses. Methods: Enrofloxacin was administered at dosages of 2.5 mg/kg of body weight to 4 horses and 5.0 mg/kg to 4 other horses. Each dose was given by the intragastric and i.v. routes, using a cross-over design. After the first intragastric dose, 5 additional doses were administered at 12-hour intervals. Enrofloxacin concentrations were measured in serum, synovial fluid, peritoneal fluid, urine, CSF, and endom...
Galbraith EA, McKellar QA.Flunixin was highly protein bound in the serum of dogs (92.2 per cent), goats (84.8 per cent) and horses (86.9 per cent). Meclofenamic acid was also highly protein bound, although there were larger differences between the extent of the binding in dogs (90.3 per cent), goats (84.7 per cent) and horses (99.8 per cent). Both flunixin and meclofenamic acid were potent inhibitors of the in vitro generation of thromboxane (Tx) B2 in blood. Flunixin inhibited the generation of TxB2 by 50 per cent of the maximum response (IC50) in dog, goat and horse blood at concentrations of 0.10, 0.02 and 0.04 micr...
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...
Egenvall A, Nødtvedt A, Roepstorff L, Bonnett B.In a world of limited resources, using existing databases in research is a potentially cost-effective way to increase knowledge, given that correct and meaningful results are gained.Nordic examples of the use of secondary small animal and equine databases include studies based on data from tumour registries, breeding registries, young horse quality contest results, competition data, insurance databases, clinic data, prescription data and hunting ability tests. In spite of this extensive use of secondary databases, integration between databases is less common. The aim of this presentation is to...
Beasley AM, Coleman GT, Kotze AC.The use of macrocyclic lactone drugs for control of equine cyathostomins is threatened by increasing levels of resistance. Detection of changes in drug sensitivity is important for effective and sustainable management of cyathostomins, however, at present such detection relies on the use of the faecal egg count reduction test, which is known to be an insensitive method. The present study therefore aimed to examine the use of a 96-well plate larval migration inhibition test for detection of resistance to macrocyclic lactone drugs in cyathostomins. We optimised conditions for migration of larvae...
Wong AS, Ho EN, Wan TS.Myo-inositol trispyrophosphate (ITPP) is a new drug capable of increasing the amount of oxygen in hypoxic tissues. Studies have shown that administration of ITPP increases the maximal exercise capacity in normal mice as well as mice with severe heart failure. The properties of ITPP make it an ideal candidate as a doping agent to enhance performance in racehorses. While there have been speculations in the horseracing industry that the covert use of ITPP is already widespread, no reported method exists for the detection of ITPP in equine biological samples. ITPP is a difficult-to-detect drug due...
Stein F, Gilliam L, Davis J, Taylor J.In a randomized crossover design study, 10 adult horses were administered crushed metronidazole tablets rectally at 20 mg/kg. Horses' rectums were either evacuated (E) or not evacuated (NE) of manure prior to the administration of the drug. Serum samples were taken over 24 hr and plasma concentrations were determined via high pressure liquid chromatography. At 15 min post-administration, group E had a significantly higher plasma concentration (p = 0.027), but there were no concentration differences at any other time points. There was large variability in relative bioavailability in the NE...
Li X, Uboh CE, Soma LR, Liu Y, Guan F, Aurand CR, Bell DS, You Y, Chen J, Maylin GA.Cathinone derivatives are new amphetamine-like stimulants that can evade detection when presently available methods are used for doping control. To prevent misuse of these banned substances in racehorses, development of a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method became the impetus for undertaking this study. Methods: Analytes were recovered via liquid-liquid extraction using methyl tert-butyl ether. Analyte separation was achieved on a hydrophilic interaction column using liquid chromatography and mass analysis was performed on a QTRAP mass spectrometer in positive elec...
Parra N, Jaume M, Boscán K, Hernández A, Mijares A, González M, Alvarado Y, Restrepo J.Trypanosoma equiperdum is the causative agent of dourine, a venereal disease in horses and donkeys. This parasite has a widely distribution, is found in Africa, Asia, Southern and Eastern Europe, Russia, Mexico and Venezuela. The T. equiperdum is morphologically indistinguishable to other Trypanozoon species, however differs from other mammalian trypanosomes due to the fact that it is primarily a tissue parasite, generating cutaneous plaques, swelling of genitalia and neurological signs. The aim of this study was to evaluate the trypanocidal effectiveness of a set of derivatives of thiosemicar...
Soma LR, Sams R, Duer W, Tobin T, Woodward C, McDonald J.The plasma and serum concentrations of phenylbutazone (PBZ) and oxyphenbutazone were measured in 158 Thoroughbred horses after various doses of PBZ wer given. All horses were competing or training at racetracks in various parts of the country. All horses used in the study had not been given PBZ 24 hours before they were placed on a specific dosage schedule. Samples were collected 24 hours after the last PBZ administration. Four grams of PBZ were given daily by stomach tube, paste, or tablet for 3 days. On day 4, 24 hours before sample collection, an IV dose of 2 g of PBZ was given, regardless ...
Emmerich IU.In 2012, two newly developed active pharmaceutical ingredients for horses and food producing animals were released on the German market for veterinary drug products. Those are the parenterally applicable first generation cephalosporin Cefalonium (Cepravin®) and the nonsteroidal anti-inflammatory drug Suxibuzone (Danilon®). Furthermore, one established veterinary active pharmaceutical ingredient is applicable to additional species: The anticoccidial Amprolium (Eimeryl®) has again been authorized for chicken and turkeys. Additionally, two veterinary drugs with a new formulation as well as thr...
Wang CC, Hartmann-Fischbach P, Krueger TR, Wells TL, Feineman AR, Compton JC.Dermorphin and HYP(6) -dermorphin are hepta-peptides and natural opioids originally isolated from the skin of South American frogs. They are more potent than morphine but less likely to produce drug tolerance and addiction. These properties make them ideal candidates for the doping of racehorses to enhance performance during competition. Dermorphin was recently classified as a Class I drug by Racing Commissioners International (RCI), indicating that it is a banned substance in equine athletes. To enforce this ban, a fast and sensitive method was developed for dermorphin and HYP(6)-dermorphin a...
Chang Y, Maylin GM, Matsumoto G, Neades SM, Catlin DH.Methods have been developed to screen for and confirm darbepoetin alfa, recombinant human EPO, and methoxy polyethylene glycol-epoetin β (PEG-epoetin β) in horse plasma. All three methods screen samples with an enzyme-linked immunosorbent assay (ELISA) and confirm by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This report focuses on PEG-epoetin β. The ELISA assay was able to detect PEG-epoetin β at 0.02 ng/mL in 50 µL of horse plasma. Many samples had high background levels of immunoreactivity; however, introducing polyethylene glycol 6000 (PEG 6000) into the samples before...
Giorgi M, Mengozzi G, Raffaelli A, Saba A.Tepoxalin is a veterinary drug registered for use in the dog as a dual inhibitor (cyclooxygenase-5 lipoxygenase). In the horse, it predominantly triggers a strong cyclooxygenase inhibition; this bias seems to be due to the action of its metabolite(s). Among these, only the RWJ-20142 is well known, while to the best of our knowledge no information is available on the other metabolites produced in vivo. Hence, the identification of its main metabolic pathway is pivotal to better understand its clinical activity. A suitable high performance liquid chromatography method has been applied to liquid ...
Eckers C, Skrabalak DS, Henion J.We describe an integrated micro-liquid chromatograph/mass spectrometer (micro-LC/MS) system capable of performing routine determinations for 1--10 ng of drugs and their metabolites extracted from biological fluids. The micro-LC is constructed from conventional "high-performance" liquid-chromatographic instrumentation by using commercially available components. The mass spectrometer is operated in the chemical ionization mode. The direct liquid introduction micro-LC/MS interface can be constructed from commercially available materials. Chromatographic and mass spectral results demonstrate the a...
Jonckheere JA, Thienpont LM, De Leenheer AP, De Backer P, Debackere M, Belpaire FM.A method has been developed for quantification of bromhexine in plasma using gas chromatography mass spectrometry with selected ion monitoring. A deuterium labelled analogue was synthesized and used as the internal standard. To evaluate the gas chromatographic electron capture detection method described earlier, 23 plasma samples have been analysed by both techniques. Although a good correlation was shown, selected ion monitoring was superior to the electron capture detection method for levels below 3 ng ml-1. The mass spectrometric method has also been used to set up a pharmacokinetic study o...
Fradette ME, Céleste C, Richard H, Beauchamp G, Laverty S.To evaluate the effects of continuous oral administration of phenylbutazone on serum and synovial fluid biomarkers of skeletal matrix metabolism in horses. Methods: 11 adult female horses without clinical or radiographic evidence of joint disease. Methods: Horses were randomly assigned to control or treatment groups. Phenylbutazone was administered orally twice daily at a dose of 4.4 mg/kg for 3 days to the treatment group and subsequently at a dose of 2.2 mg/kg for 7 days. Serum and radiocarpal synovial fluid samples were obtained at baseline and thereafter at regular intervals for 4 weeks. B...
Gałęcki K, Kowalska-Baron A.In this study, the influence of heavy-atom perturbation, induced by the addition of iodide ions, on the fluorescence and phosphorescence decay parameters of some single tryptophan containing serum albumins isolated from: human (HSA), equine (ESA) and leporine (LSA) has been studied. The obtained results indicated that, there exist two distinct conformations of the proteins with different exposure to the quencher. In addition, the Stern-Volmer plots indicated saturation of iodide ions in the binding region. Therefore, to determine quenching parameter, we proposed alternative quenching model and...
Smith KM, Maxwell L, Gull T, Payton ME, Gilmour MA.To establish the effect of storage in a constant-rate infusion (CRI) pump on the sterility and stability of voriconazole 1% solution. Methods: Nine vials of voriconazole (Vfend(®) I.V.) 1% solution were prepared. Approximately half of each solution was used to prime a commercially available CRI pump with attached subpalpebral lavage system (CRI/SPL unit) with the remaining solution stored in the commercial glass vial. Three CRI/SPL units and their three corresponding vials were stored at one of three temperatures: 23 °C, 33 °C, and 40 °C. The CRI pumps ran for 7 days, and the vials were st...
Matayoshi M, Kudaka J.Between 1992 and 2007, a total of 86 isolates of Salmonella enterica Weltevreden were obtained from clinical human samples (n = 41), 45 farm animals and their environment on 20 farms, including poultry (n = 25), beef cattle (n = 5), swine (n = 5), dairy cattle (n = 3), mice (n = 2), pony (n = 1), fly (n = 1) and feed samples (n = 3), in Okinawa Prefecture, Japan. Only seven isolates (8.1%) of the isolates were resistance to one or more antimicrobial agents tested; six streptomycin (7.0%), six oxytetracycline (7.0%), two ampicillin (2.3%), two kanamycin, (2.3%), two chloramphenicol (2.3%), two ...
Yamada M, Aramaki S, Okayasu T, Hosoe T, Kurosawa M, Kijima-Suda I, Saito K, Nakazawa H.Anabolic steroids with the 17alpha-methyl,17beta-hydroxyl group, which were developed as oral formulations for therapeutic purposes, have been abused in the field of human sports. These anabolic steroids are also used to enhance racing performance in racehorses. In humans, structurally related 17alpha-methyltestosterone (MTS) and mestanolone (MSL), which are anabolic steroids with the 17alpha-methyl,17beta-hydroxyl group, have metabolites in common. The purpose of this study was to determine metabolites common to these two steroids in horses, which may serve as readily available screening targ...
Ayres JW, Pearson EG, Riebold TW, Chang SF.The pharmacokinetics of theophylline and dyphylline were determined after IV administration in horses. In a preliminary experiment, the usual human dosage (milligram per kilogram) of each drug was given to 1 horse. Results were used to calculate dosages for a cross-over study, using 6 horses for each drug. Theophylline plasma concentrations decreased triexponentially in 5 of 6 healthy horses after IV infusion of 10 mg of aminophylline/kg of body weight for 16 to 32 minutes. In the 6 horses, total body elimination rate constants were variable, and the half-life of theophylline was 9.7 to 19.3 h...
Mitema ES, Sangiah S, Martin T.Monensin is extremely toxic to some domestic animals, like the equine species, if they ingest poultry or cattle rations containing the drug. From a treatment standpoint, no specific compounds are known to alleviate or interact with monensin. Effects of some cardiovascular drugs which antagonize calcium influx in cardioskeletal and smooth muscles were evaluated in mice receiving varying lethal doses (80, 100, 120 or 140 mg/kg ip). Calcium channel blockers (verapamil, diltiazem and lidocaine), a calmodulin antagonist (chlorpromazine), adrenergic receptor blockers (yohimbine, tolazoline and propr...
Stammwitz V, Honnens Ä, Hochhuth D, Schuberth HJ.Between 2015 and 2017, a marked increase of anaphylactic-like reactions after intravenous administration of gentamicin was observed first in horses and, later, also in humans. This worldwide issue led to safety measures including product recalls and safety warnings. Here, a German Marketing Authorization Holder (MAH) of an early and intensely affected veterinary product containing gentamicin describes the clinical approach of the company to analyze the root cause and identify the causative agent in the active pharmaceutical ingredient (API). The pharmacovigilance data of the MAH are presented,...
Choi TLS, Wong JKY, Kwok WH, Curl P, Mechie S, Wan TSM.Methylstenbolone (2,17α-dimethyl-5α-androst-1-en-17β-ol-3-one) is a synthetic anabolic and androgenic steroid (AAS) sold as an oral 'nutritional supplement' under the brand names 'Ultradrol', 'M-Sten' and 'Methyl-Sten'. Like other AASs, methylstenbolone is a prohibited substance in both human and equine sports. This paper describes the studies of the in vitro and in vivo metabolism of methylstenbolone in horses using LC/HRMS, GC/MS and GC/MS/MS. Phase I in vitro metabolic study of methylstenbolone was performed using homogenised horse liver. Hydroxylation was the only biotransformation obse...
Muir WW, Lerche P, Erichson D.Studies have demonstrated the clinical usefulness of propofol for anaesthesia in horses but the use of a concentrated solution requires further investigation. Objective: To determine the anaesthetic and cardiorespiratory responses to a bolus injection of 10% propofol solution in mature horses. Methods: Three randomised crossover experimental trials were completed. Trial 1: 6 horses were selected randomly to receive 10% propofol (2, 4 or 8 mg/kg bwt i.v.). Trial 2: 6 horses received 1.1 mg/kg bwt i.v. xylazine before being assigned at random to receive one of 5 different doses (1-5 mg/kg bwt) o...
Stevenson AJ, Weber MP, Trudel R, Leavitt R, Woodard D, Todi F, Mendonca M, Robillo V, Young L, Kacew S.Analytical procedures were developed to monitor furosemide concentrations in post-race serum and urine samples obtained from horses participating in an exercise-induced pulmonary haemorrhage (EIPH) program. High performance liquid chromatography with ultraviolet light detection proved a reliable, sensitive method for measuring urinary furosemide concentrations up to 12 h after administration of either 150 or 250 mg of the drug to race horses. However, this method was unreliable for determination of serum furosemide concentration. High performance liquid chromatography with fluorescence detecti...
Page AE, Johnson M, Parker JL, Jacob O, Swan M, Adam E.The use of dexamethasone to control equine asthma is a common and effective treatment. Although short-term systemic dexamethasone treatment has not been shown to induce systemic immunosuppression in the horse, the goal of this study was to determine whether inhaled ciclesonide, an FDA-approved drug for the treatment of equine asthma, exerts any systemic immunosuppressive effects when compared to dexamethasone-treated and untreated horses. Eighteen light, mixed breed horses, ranging in age from 3 to 8 years of age, were used for this study and randomly assigned to one of three treatment groups:...
Araújo RA, Sales NAA, Basile RC, Feringer-Junior WH, Apparício M, Ferraz GC, Queiroz-Neto A.Firocoxib is a non-steroidal anti-inflammatory drug specifically formulated for veterinary medicine and selectively acts on inhibiting the cyclooxygenase 2 enzyme (COX-2). This study evaluated the possible adverse effects of administering oral therapeutic firocoxib on gastric mucosa, hematological parameters, coagulation cascade, and hepatic and renal biochemistry in healthy horses. Nine clinically healthy Arabian horses, approximately 9 years old, received 0.1 mg/kg of oral firocoxib for 14 days. The gastroscopic examination was conducted 1 day before starting treatment (D0) and two days afte...
Scantamburlo G, Nofziger C, Paulmichl M, Vanoni S.Because of their importance as companion animals or as racehorses, horses can be treated with various drugs. Although it is known that drug withdrawal times can vary for each horse, pharmacogenetics for these animals has not been adequately studied and requires further development. Since is responsible for the metabolism of 25-30% of drugs in humans, including some used to treat horses, a study of the family in horses was conducted to define its genetic structure as well as its expression pattern in the liver. Unassigned: Genomic DNA extracted from venous blood and mRNA from fresh liver tiss...
Andersen C, Jacobsen S, Uvebrant K, Griffin JF, Vonk LA, Walters M, Berg LC, Lundgren-Åkerlund E, Lindegaard C.Integrin α10β1-selected mesenchymal stem cells (integrin α10-MSCs) have previously shown potential in treating cartilage damage and osteoarthritis (OA) and in animal models . The aim of this study was to further investigate disease-modifying effects of integrin α10-MSCs. Methods: OA was surgically induced in 17 horses. Eighteen days after surgery, horses received 2 × 10 integrin α10-MSCs intra-articularly or were left untreated. Lameness and response to carpal flexion was assessed weekly along with synovial fluid (SF) analysis. On day 52 after treatment, horses were euthanized, and carp...
Ishii H, Ishikawa Y, Mizobe F, Nomura M, Yamanaka T, Tanabe S, Nagata SI, Yamada M, Leung GN.Osilodrostat is an inhibitor of 11-beta-hydroxylase (CYP11B) and is used for the treatment of Cushing's disease but also categorized as an anabolic agent. The use of osilodrostat is prohibited in horseracing and equestrian sports. To the best of our knowledge, this is the first metabolic study of osilodrostat in equine plasma. Methods: Potential metabolites of osilodrostat were identified by differential analysis using data acquired from pre- and post-administration plasma samples after protein precipitation with liquid chromatography electrospray ionization high-resolution mass spectrometry (...
