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.
Bryant CE, Thompson J, Clarke KW.Medetomidine was administered to sheep and horses at a dose rate of 5 microg kg(-1) (i.v.). Heart rate and blood pressure were recorded. Medetomidine induced bradycardia and a biphasic blood pressure response consisting of a transient hypertension followed by hypotension. Administration of prazosin (an alpha1 adrenoceptor antagonist; 100 microg kg(-1), i.v.) had no effect on the cardiovascular response to medetomidine (5 microg kg(-1), i.v.), but inhibited the cardiovascular response of methoxamine (an alpha1 adrenoceptor agonist; 75 microg kg(-1), i.v.). L-659,066 (an alpha2 adrenoceptor anta...
Dyke TM, Sams RA, Thompson KG, Ashcraft SM.To compare pharmacokinetics of eltenac after first and last IV administrations (0.5 mg/kg), using a multiple dosing schedule. Methods: 6 adult mares. Methods: Eltenac (50 mg/ml) was administered IV at a dosage of 0.5 mg/kg of body weight every 24 hours for days 0 through 4. On days 0 and 4, blood samples were collected before, then periodically for 8 hours after eltanac administration. Concentration of eltenac in plasma samples was determined by use of high-performance liquid chromatography. Results: On day 0, median area under the plasma eltenac concentration versus time curve (AUC) was 6.77 ...
Queiroz-Neto A, Zamur G, Gonçalves SC, Carregaro AB, Mataqueiro MI, Harkins JD, Tobin T.Amitraz, an acaricide used to control ectoparasites in animals has a complex pharmacological activity, including alpha2-adrenergic agonist action. The purpose of this research was to investigate the possible antinociceptive and/or sedative effect of amitraz in horses. The sedative effect of the intravenous (i.v.) injection of dimethylformamide (DMF, 5 mL, control) or amitraz (0.05, 0.10, 0.15 mg/kg), was investigated on the head ptosis test. The participation of alpha2-adrenergic receptors in the sedative effect provoked by amitraz was studied by dosing yohimbine (0.12 mg/kg, i.v.). To measure...
Törneke K, Ingvast Larsson C, Appelgren LE.Beta2-adrenoceptor agonists are used as bronchodilators in both humans and horses. Of these drugs, clenbuterol is the one most frequently used when treating chronic obstructive pulmonary disease in the horse, while salbutamol and terbutaline are used in the treatment of human asthma. Little is known of the properties of the latter two drugs in equine medicine. We have compared salbutamol and terbutaline with clenbuterol in relation to their ability to relax muscle strips from equine tracheal muscle, precontracted with 40 nM carbachol, in tissue chambers. The affinities of these drugs to the be...
Ramirez S, Seahorn TL, Williams J.This report describes a renal ultrasonographic abnormality (medullary rim sign), which was identified in 2 separate cases of spontaneously occurring disease associated with chronic and acute overdosage of phenylbutazone therapy. In horses, medullary rim sign has only been documented in neonatal foals experimentally administered large doses of phenylbutazone.
Szöke MO, Blais D, Cuvelliez SG, Lavoie JP.To evaluate the cardiovascular and respiratory effects of buprenorphine administered intravenously in clinically normal horses and horses with chronic obstructive pulmonary disease (COPD). Methods: 5 clinically normal horses and 5 horses with COPD that were in partial clinical remission (period A) or were having an acute attack of airway obstruction (period B). Methods: Pulmonary function testing, arterial blood gas analysis, and arterial blood pressure measurements were performed before and after a single intravenous bolus of buprenorphine (3 microg/kg of body weight). Respiratory rate (f), t...
Magdesian KG, Hogan PM, Cohen ND, Brumbaugh GW, Bernard WV.To evaluate pharmacokinetics of a high dose of gentamicin administered i.v. or i.m. to horses. Methods: Repeated-measures study. Methods: 6 clinically normal female adult stock-type horses. Methods: All horses were given gentamicin (6.6 mg/kg [3 mg/lb] of body weight), i.v. and i.m., in a two-way cross-over design. Serum gentamicin concentrations were measured during a 24-hour period. Results: Plasma concentration curves were consistent with a two-compartment model. Maximum plasma gentamicin concentrations were 71.9 +/- 15.7 micrograms/ml (0 hours after injection) and 22.0 +/- 4.9 micrograms/m...
Garbís SD, Hanley L, Kalita S.Thiazide-based diuretics are included in the list of banned drugs in the horse-racing industry. One effect of their misuse is increased urine flow, contributing to dilution of other doping agents. Their determination is essential in ensuring compliance to horse-racing regulation. This study evaluates the feasibility of using liquid chromatography/mass spectrometry (LC/MS) with electrospray and atmospheric pressure chemical ionization interfaces to analyze thiazidic diuretics in equine urine samples. Existing LC and gas chromatography/MS methods are limited in their applicability to thiazide an...
Dyke TM, Sams RA, Hinchcliff KW.The effects of exercise training on hepatic function in horses were determined by studying the plasma clearance of antipyrine (20 mg/kg iv) in adult mares that either underwent treadmill training for 5 wk (n = 7) or remained in box stalls for the same time period (n = 6). Training consisted of treadmill exercise at 60% (12 min/day) and 90% (3 min/day) of pretraining maximal oxygen consumption (V(O2)max) for 6 days/wk for 5 wk. V(O2)max and velocity to obtain a blood lactate concentration of 4 mmol/l were significantly increased (from 129 to 149 ml x min-1 x kg-1 and from 5.6 to 6.1 m/s, respec...
Dyke TM, Hubbell JA, Grosenbaugh DA, Beard W, Mitten L, Sams RA, Hinchcliff KW.The pharmacokinetics of furosemide were investigated in anaesthetized horses with bilateral ureteral ligation (BUL) with (n = 5) or without (n = 5) premedication with phenylbutazone. Horses were administered an intravenous (i.v.) bolus dose of furosemide (1 mg/kg) approximately 60-90 min after BUL. Plasma samples collected up to 3 h after drug administration were analysed by a validated high performance liquid chromatography method. Median plasma clearance (CLp) of furosemide in anaesthetized horses with BUL was 1.4 mL/min/kg. Apparent steady state volume of distribution (Vd(ss)) ranged from 1...
Young LE, Blissitt KJ, Clutton RE, Molony V.To evaluate temporal hemodynamic effects of dobutamine in horses anesthetized with halothane. Methods: 8 adult Thoroughbreds. Methods: Anesthesia was induced by i.v. administration of romifidine and ketamine and maintained using halothane in oxygen. After 60 minutes, dobutamine was administered i.v. for 60 minutes at 4 micrograms/kg of body weight/min. Measurements of left ventricular function were obtained by transesophageal echocardiography and cardiac catheterization. Results: Mean, systolic, diastolic, aortic, pulmonary arterial, and left and right ventricular end-diastolic and systolic pr...
Doherty TJ, Frazier DL.This study investigated the effect of lidocaine i.v. on halothane minimum alveolar concentration (MAC) in ponies. Six ponies were anaesthetised with thiopentone and succinylcholine, intubated and anaesthesia maintained with halothane. Ventilation was controlled and blood pressure maintained within clinically acceptable limits. Following a 2 h equilibration period, baseline halothane MAC was determined. The ponies were then given a loading dose of lidocaine (2.5 or 5 mg/kg bwt) or saline over 5 min, followed by a constant infusion of lidocaine (50 or 100 microg/kg/min, or saline, respectively)....
Harkins JD, Mundy GD, Stanley S, Woods WE, Sams RA, Richardson DR, Grambow SC, Tobin T.Isoxsuprine is reported to be a peripheral vasodilator used in human and veterinary medicine to treat ischaemic vascular disease. In horses, it is generally administered orally to treat navicular disease and other lower limb problems. To define the scope and duration of its pharmacological responses after oral administration, 6 horses were dosed with isoxsuprine HCl (1.2 mg/kg bwt) q. 12 h for 8 days and then tested to assess the duration and extent of pharmacological actions. There was no significant difference between isoxsuprine and control treatment values for heart rate, spontaneous activ...
Valk N, Doherty TJ, Blackford JT, Abraha TW, Frazier DL.The effect of cisapride pretreatment on gastric emptying in horses was determined by measuring serum concentrations of acetaminophen, a drug known to be readily absorbed in the small intestine but not in the stomach. The time to reach maximum serum acetaminophen concentrations (Tmax), the maximum serum concentrations (Cmax) and the area under the serum acetaminophen concentration vs. time curves (AUC) were compared among treatment groups. In the first part of the study, the effect of orally administered cisapride (0.1, 0.2 and 0.4 mg/kg bwt) on gastric emptying was examined in 6 normal fasted ...
Soliman GA.The pharmacokinetic behaviour of gentamicin sulphate (3.4 mg/kg bwt) was studied following its intramuscular injection to a group of horses and to another group of horses premedicated with sodium methyl arsinate (2 mg/kg bwt) or imidocarb dipropionate (4.8 mg/kg bwt). Considerable differences were observed in the pharmacokinetics of gentamicin in pre-medicated horses and in horses which had received the antibiotic alone. Peak serum concentration of gentamicin (9.85 +/- 0.05 and 11.15 +/- 0.15 micrograms/ml) were attained within 1.45 +/- 0.05 and 0.92 +/- 0.04 h in arsinate and imidocarb-medica...
Oukessou M, Alsouss L.The body disposition of sulfadimidine (SDM), sulfadiazine (SDZ), sulfamethoxypyridazine (SMPZ) and a trimethoprim-sulfadimethoxine combination (TMP-SDMX) was investigated in the donkey. The four sulfonamides and TMP were injected intravenously at doses of 20 mg/kg (SDM, SDZ, SMPZ), 12.5 mg/kg (SDMX) and 2.5 mg/kg (TMP). The body clearance (ClB) of SDZ (1.70 +/- 0.14 ml/min/kg) was significantly higher than those of SDM (1.13 +/- 0.18 ml/min/kg), SMPZ (1.10 +/- 0.09 ml/min/kg) and SDMX (0.75 +/- 0.04 ml/min/kg). In contrast, the volume of distribution at steady state (Vss) was similar for the f...
Chua HC, Stewart B, Lim BH, Lee HK.A chromatographic method was developed to detect and confirm the presence of chlorpropamide (I) in horse plasma samples, for antidoping control. The plasma sample (1 ml) was extracted with dichloromethane and screened by high-performance liquid chromatography, and confirmation of the drug's presence was accomplished by using gas chromatography-mass spectrometry (GC-MS). The limit of detection was found to be 3.5 ng/ml at a signal-to-noise ratio of three. Derivatization of I with N,O-bis-(trimethylsilyl)trifluoroacetamide with 1% trimethylchlorosilane allowed for highly stable, accurate and sen...
Soma LR, Uboh CE.Furosemide has been used empirically and has been legally approved for many years by the US racing industry for the control of exercise-induced pulmonary haemorrhage (EIPH) or bleeding. Its use in horses for this purpose is highly controversial and has been criticized by organizations outside and inside of the racing industry. This review concentrates on its renal and extra-renal actions and the possible relationship of these actions to the modification of EIPH and changes in performance of horses. The existing literature references suggest that furosemide has the potential of increasing perfo...
Hills BA, Ethell MT, Hodgson DR.This study was undertaken to determine whether glucocorticosteroids promote the secretion of lubricating surfactant, i.e. surface-active phospholipid (SAPL), into the joint. A standard clinical dose (100 mg) of methylprednisolone acetate (MPA) in 2.5 ml of saline was injected into the load-bearing right radiocarpal joint of five horses and 2.5 ml of saline injected into each of the contralateral joints used as controls. Synovial fluid (SF) was aspirated from all 10 joints before injection and at intervals of 16 and 32 h after injection, and then analysed by standard methods. All test joints sh...
Gómez de Segura IA, De Rossi R, Santos M, López San-Roman J, Tendillo FJ, San-Roman F.To determine the analgesic, sedative, and cardiopulmonary effects of epidural ketamine in the horse. Methods: Six healthy horses (three males and three females) weighing between 350 and 450 kg. Methods: Three doses of ketamine were selected (0.5, 1, 2 mg/kg). Two months before the beginning of experiments, the carotid artery was exteriorized, and 1 week before experiments began, an epidural catheter was placed percutaneously in all animals with the tip located 12 cm cranially in the midsacrum. One week later, either saline (control) or one of three doses of ketamine was injected epidurally. Ea...
Brink P, DeGraves F, Ravis WR, Johansen D, Campbell JD, Duran SH.To determine intravascular and intrasynovial pharmacokinetics of the R and S enantiomers of ketoprofen after i.v. and i.m. administration to horses. Methods: 6 healthy adult mares. Methods: Horses were weighed and ketoprofen (2.2 mg/kg of body weight) was administered i.v. Blood and synovial fluid samples were obtained and analyzed for concentrations of the R and S enantiomers by means of a modified reverse-phase stereospecific high-pressure liquid chromatographic method. Three weeks later, the procedure was repeated, except that ketoprofen was given IM. Protein binding of ketoprofen enantiome...
Short CR, Sams RA, Soma LR, Tobin T.The primary reason for developing the ARCI Uniform Classification of Foreign Substances was to give stewards and other racing regulators guidelines to assist them in understanding the relative performance effects and general offensiveness to the Rules of Racing of various drugs and medications. As such, these guidelines have been very useful in the world of racing regulation--officially or unofficially--because this classification system, for the first time, places a relative number on the inappropriateness of any one of more than 750 agents appearing in forensic samples taken from racing hors...
Chou CC, Chen CL, Asbury AC, Webb AI, Vickroy TW.To develop an ELISA that is sensitive and suitable for measurement of immunoreactive acepromazine (ACP) in horse serum and urine and to determine the acute effects of exercise on immunoreactive ACP values in Thoroughbreds. Methods: 12 healthy Thoroughbreds (5 mares, 5 geldings, 2 stallions), aged 2 to 8 years. Methods: A commercially available antibody and a horseradish peroxidase-conjugated oxime derivative of immunoreactive ACP were used to develop a one-step ELISA. Horses were used in a crossover design study to evaluate possible effects of treadmill exercise on serum and urine ACP concentr...
Merritt AM, Burrow JA, Hartless CS.To evaluate the effect on equine duodenal motility of some analgesic agents commonly used to treat colic. Methods: 4 healthy adult healthy horses--2 mares and 2 geldings--which were carrying an indwelling gastric cannula made of silastic rubber. One horse also carried 2 long-term indwelling bipolar electrodes that had been sutured onto the duodenum and jejunum. Methods: To ensure an empty stomach, solid food was withheld from horses for around 20 hours prior to an experiment. Using videoendoscopic guidance, an 8-F catheter with 3 small, discrete pressure sensors was passed through the gastric ...
Guglick MA, MacAllister CG, Clarke CR, Pollet R, Hague C, Clarke JM.To determine pharmacokinetics of i.v., i.m., and oral administration of cefepime in horses and to compare pharmacokinetics of i.m. administration of cefepime with those of ceftiofur sodium. Methods: 6 clinically normal adult horses. Methods: Horses received 3 doses of cefepime (11 mg/kg of body weight, PO; 2.2 mg/kg, i.v.; and 2.2 mg/kg, i.m.) and 1 dose of ceftiofur (2.2 mg/kg, i.m.). Two horses also received L-arginine, p.o. and i.v., at doses identical to those contained in the cefepime dihydrochloride-L-arginine preparations previously administered. Blood samples were collected for 24 hour...
Kuroda T, Nagata SI, Tamura N, Mita H, Kusano K, Mizobe F, Takizawa Y, Fukuda K, Kasashima Y.To investigate the pharmacokinetics and antihistaminic effects (pharmacodynamics) of olopatadine in a small population of healthy horses after administration via nasogastric tube. Methods: 4 healthy adult Thoroughbreds. Methods: Olopatadine (0.1 mg/kg, once) was administered via nasogastric tube. Blood samples were collected at predetermined time points for pharmacokinetic analyses of the drug in plasma. Olopatadine effects were investigated by measurement of cutaneous wheals induced by ID histamine injection (0.1 mL [10 μg]/injection) at predetermined time points. Inhibition effect ratios we...
Scotty NC, Evans TJ, Giuliano E, Johnson PJ, Rottinghaus GE, Fothergill AW, Cutler TJ.Lufenuron is a benzoylphenyl urea-derived insecticide that has been recently introduced as a novel treatment for fungal infections in horses. The purposes of this study were to determine (1) the in vitro efficacy of lufenuron against Aspergillus and Fusarium spp. and (2) the ability of lufenuron to reach efficacious blood concentrations after PO administration in horses. Fungal colonies isolated from diseased equine corneas were tested against lufenuron solutions up to 700 microg/mL. Twenty-one adult horses received 1 of 3 PO lufenuron treatment regimens: 5 mg/kg body weight (BW) q24h for 3 da...
Dirikolu L, Mollett BA, Troppmann A, Woods WE, Bratton C, Cashman CP, Schroedter D, Mayer B, Lehner AF, Karpiesiuk W, Hughes C, Boyles J, Harkins JD....Single doses of one, three, and six actuations (120 micro g albuterol/actuation) and multiple daily doses (six actuations per dose four times daily) for 5 days of aerosol albuterol sulfate were sequentially administered to each of six horses using an equine inhaler device (Torpex, 3M Animal Care Products, St. Paul, MN [corrected] and Boehringer Ingleheim Vetmedica, Inc., St. Joseph, MO [corrected]). A 2-week washout period was allowed between each dose. ELISA testing revealed no evidence of albuterol in urine at 24 hours after any single-dose administration. Results indicated that 48 hours or ...
Philip M, Karakka Kal AK, Subhahar MB, Karatt TK, Mathew B, Perwad Z, Graiban FM, Caveney MR, Sayed R, Kadry AM.According to previous research, aminorex is the major metabolite of levamisole; however, in the screening of levamisole-positive racehorse urine and plasma samples, aminorex could only be detected in trace amounts or not at all. In forensic laboratories, hydroxy levamisole and its phase II conjugates make it easier to confirm levamisole misuse and to differentiate between the abuse of levamisole and aminorex. This study aimed to identify the major levamisole metabolites that can be detected along with the parent drug. Methods: The study describes levamisole and its metabolites in thoroughbred ...
Dyke TM, Hinchcliff KW, Sams RA.The objectives of this study were to determine the effect of phenylbutazone premedication on the pharmacokinetics and urinary excretion of frusemide in horses; and on frusemide-induced changes in urinary electrolyte excretion. Six Standardbred mares were used in a 3-way crossover design. The pharmacokinetics and renal effects of frusemide (1 mg/kg bwt i.v.) were studied with and without phenylbutazone premedication (8.8 mg/kg bwt per os 24 h before, followed by 4.4 mg/kg bwt i.v. 30 min before frusemide administration). A control (saline) treatment was also studied. Administration of frusemide...
Mori M, Ichibangase T, Yamashita S, Kijima-Suda I, Kawahara M, Imai K.In the doping tests currently used in horse racing, prohibited substances or their metabolites are usually directly detected in urine or blood samples. However, despite their lasting pharmaceutical effects, some prohibited substances are rapidly eliminated from horse urine and blood, making them difficult to detect. Therefore, new indirect biomarkers for doping, such as plasma proteins that are increased by the prohibited substances, have recently attracted much attention. Here, a fluorogenic derivatization-liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS) method was adopted for hor...
Jaraiz V, Rodriguez C, San Andres MD, Gonzalez F, San Andres MI.A disposition and bioequivalence study with a suxibuzone granulated and a suxibuzone paste oral formulation was performed in horses. Suxibuzone (SBZ) is a nonsteroidal anti-inflammatory drug, which was administered to horses (n = 6) at a dosage of 19 mg/kg bwt by the oral route (p.o.) in a two period cross-over design. Suxibuzone is very rapidly transformed into its main active metabolites, phenylbutazone (PBZ) and oxyphenbutazone (OPBZ). Therefore plasma and synovial fluid concentrations of SBZ, PBZ and OPBZ were simultaneously measured by a sensitive and specific high-performance liquid chro...
McKenzie EC, Garrett RL, Payton ME, Riehl JH, Firshman AM, Valberg SJ.Dantrolene sodium is used to prevent exertional rhabdomyolysis in predisposed horses. Food intake might negatively impact dantrolene bioavailability in horses; however, prolonged feed restriction might be detrimental to performance. Objective: To determine a minimum duration of feed restriction that would optimise plasma dantrolene concentrations in horses after nasogastric administration. It was hypothesised that feed restriction for 4, 8 or 12 h before dantrolene administration would result in higher plasma dantrolene concentrations than achieved with no feed restriction before treatment. Me...
May SA, Hooke RE, Lees P.There is increasing evidence that the proteoglycan-degrading neutral metalloproteinase, stromelysin, is a key enzyme in the pathogenesis of osteoarthrosis. Equine synovial lining cells were stimulated in vitro to produce stromelysin, and phenylbutazone, flunixin, betamethasone, sodium hyaluronate and polysulphated glycosaminoglycan (PSGAG) were tested for their ability to inhibit the action of this enzyme on 14C-labelled casein substrate. Only PSGAG possessed inhibitory activity at concentrations likely to be achieved therapeutically in the equine fetlock joint.
Stevenson AJ, Weber MP, Todi F, Young L, Beaumier P, Kacew S.Plasma and urinary concentrations of procaine were examined in Standardbred mares after subcutaneous administration of various doses (80 mg to 1600 mg) of procaine hydrochloride. Regardless of dose, peak plasma procaine values occurred within 1 h, but remained detectable in a dose-dependent manner, with procaine present at 1 h with the 80 mg dose and 6 h at the 1600 mg dose. Similarly, peak urinary procaine concentrations were attained within 1.5 to 3 h, irrespective of dose, while detection time was dose-dependent, being 23 h for 80-200 mg doses but as long as 30-54 h with the 1600 mg dose. W...
Button C, Gross DR, Johnston JT, Yakatan GJ.The pharmacokinetics of IV administered digoxin and the bioavailability of intragastrically administered powdered digoxin tables suspended in water were investigated in 6 clinically normal adult horses by 125I radioimmunoassay. The effect of 3 to 5 sequential IV doses of 5 micrograms of digoxin/kg of body weight at 2-hour intervals on a left ventricular index of contractility (Vmax) was assessed in 5 clinically normal horses. Standard pharmacokinetic equations and mean pharmacokinetic variables were used to derive parenteral and oral (loading and maintenance) doses for digoxin in horses. The c...
Knych HK, McKemie DS, Kass PH, Stanley SD, Blea J.Ketoprofen is an anti-inflammatory drug that is commonly administered to racehorses for the alleviation of musculoskeletal pain and inflammation. This study represents a comprehensive examination of the metabolism (in vivo and in vitro), pharmacokinetics and ex vivo pharmacodynamics, of ketoprofen in horses. The in vitro metabolism as well as specific enzymes responsible for metabolism was determined by incubating liver microsomes and recombinant CYP450 and UGT enzymes with ketoprofen. For the in vivo portion, 15 horses were administered a single intravenous dose of 2.2-mg/kg ketoprofen. Blood...
Douwes RA, van der Kolk JH.The use of dimethyl sulphoxide in equine medicine is discussed with special reference to trauma of the central nervous system, chronic endometritis, trauma of the locomotor apparatus, and ischaemic bowel pathophysiology. The ability of dimethyl sulphoxide to reduce connective tissue formation might be of interest in abdominal surgery. The anti-inflammatory effect of dimethyl sulphoxide is used in the treatment of muscle trauma, tendinitis, laminitis, and arthritis. Dimethyl sulphoxide can potentiate the effects of other drugs. The most common dose is 1 g/kg body weight intravenously up to a 40...
McGrath CJ.Respiratory minute volume, blood volume, RBC mass and cardiac output increase while the functional residual capacity decreases during late pregnancy. General anesthetics reach the fetus in high concentrations and tend to persist in the fetus after delivery. Use of small doses of a combination of anesthetics is recommended. Ephedrine increases vascular tone and cardiac output. Glycopyrrolate and fentanyl-droperidol are used to restrain sows for cesarean section. Morphine alone or with acepromazine works well in depressed sows. Acepromazine or xylazine, used with ketamine, is good in restraining...
Delbeke FT, Debackere M, Vynckier L.A high-performance liquid chromatographic method to measure urinary indomethacin levels is described. In 0.5 ml urine, 1 micrograms/ml of indomethacin could be detected. Alkaline hydrolysis of urine resulted in the decomposition of indomethacin. When two suppositories of Indocid corresponding to 200 mg indomethacin were administered rectally to four horses the drug was rapidly absorbed and remained detectable in urine from 1 to 12 h. The excretion rate peaked after 2-3 h while the maximal concentration ranged from 18.5 to 80.6 micrograms/ml. Only 8 to 16% of the indomethacin dose was eliminate...
el-Komy AA.The pharmacokinetics of piperacillin (430 mg/kg.b.wt.) and cephapirin (20 mg/kg.b.wt.) were investigated following a single intravenous and intramuscular injection in normal mares. The serum concentration-time curve following a single intravenous injection of both antibiotics obeyed a two-compartment open model. After intravenous dose, piperacillin and cephapirin were transferred from central to peripheral compartment (k12) with values 0.46 and 0.52 h-1, while their passages from peripheral to central compartment (k21) were equal to 0.56 and 0.49 h-1, respectively. The elimination half-lives [...
Amaral A, Cebola N, Szóstek-Mioduchowska A, Rebordão MR, Kordowitzki P, Skarzynski D, Ferreira-Dias G.Myeloperoxidase is an enzyme released by neutrophils when neutrophil extracellular traps (NETs) are formed. Besides myeloperoxidase activity against pathogens, it was also linked to many diseases, including inflammatory and fibrotic ones. Endometrosis is a fibrotic disease of the mare endometrium, with a large impact on their fertility, where myeloperoxidase was shown to induce fibrosis. Noscapine is an alkaloid with a low toxicity, that has been studied as an anti-cancer drug, and more recently as an anti-fibrotic molecule. This work aims to evaluate noscapine inhibition of collagen type 1 (C...
Chay S, Woods WE, Nugent TE, Weckman T, Houston T, Sprinkle F, Blake JW, Tobin T, Soma LR, Yocum J.Experiments to determine the residual plasma concentrations of phenylbutazone and its metabolites found in horses racing on a 'no-race day medication' or 24-h rule were carried out. One dosing schedule (oral-i.v.) consisted of 8.8 mg/kg (4 g/1000 lbs) orally for 3 days, followed by 4.4 mg/kg (2 g/1000 lbs) intravenously on day 4. A second schedule consisted of 4.4 mg/kg i.v. for 4 days. The experiments were carried out in Thoroughbred and Standardbred horses at pasture, half-bred horses at pasture, and in Thoroughbred horses in training. After administering the i.v. schedule for 4 days to Thor...
Luethy D, Robinson MA, Stefanovski D, Haughan J, Torcivia C, Kowalski A, Ford M, You Y, Missanelli J, Slack J.Cardiac drugs with defined pharmacological parameters in horses are limited. The objective of this study was to characterize the pharmacokinetic properties and cardiovascular effects of intravenous and oral metoprolol tartrate (MET) in horses. In a 2-period randomized cross-over design, MET was administered IV (0.04 mg/kg) and PO (6 mg/kg) once to six healthy adult horses. Horses were monitored via continuous telemetry and non-invasive blood pressure (NIBP). Blood samples were serially collected for 72 h post-administration, and concentrations were determined by LC-MS/MS. Pharmacokinetics w...
Kilcoyne I, Nieto JE, Galuppo LD, Dechant JE.To determine the median time to maximum concentration (t) of amikacin in the synovial fluid of the tarsocrural joint following IV regional limb perfusion (IVRLP) of the drug in a saphenous vein of horses. Methods: 7 healthy adult horses. Methods: With each horse sedated and restrained in a standing position, a 10-cm-wide Esmarch tourniquet was applied to a randomly selected hind limb 10 cm proximal to the point of the tarsus. Amikacin sulfate (2 g diluted with saline [0.9% NaCl] solution to a volume of 60 mL) was instilled in the saphenous vein over 3 minutes with a peristaltic pump. Tarsocrur...
Atwal OS, McDonell W.The pulmonary intravascular macrophages (PIMs) of equines contain a unique electron-dense surface coat that is predominantly composed of lipoproteins. A single exposure of inhalatory halothane causes mobilization of the surface coat into the endocytotic system of the PIMs, followed by expansion of the Golgi apparatus and its enrichment with acid phosphatase. Simultaneously, the cells of the lymphocytic series show hyperplasia in the form of mitotic changes inside the microvascular compartment of the lung. Halothane is known to cause acute and chronic hepatotoxicity because of its biotransforma...
Fernández-Varón E, Ayala I, Marín P, Carrión A, Martos N, Escudero E, Cárceles CM.Danofloxacin is a fluoroquinolone developed for veterinary medicine showing an excellent activity. However, danofloxacin pharmacokinetics profile have not been studied in horses previously. Objective: To study the pharmacokinetics following i.v., i.m. and intragastric (i.g.) administration of 1.25 mg/kg bwt danofloxacin to 6 healthy horses. Methods: A cross-over design was used in 3 phases (2 x 2 x 2), with 2 washout periods of 15 days (n = 6). Danofloxacin (18%) was administered by i.v. and i.m. routes at single doses of 1.25 mg/kg bwt. For i.g. administration an oral solution was prepared an...
Chay S, Woods WE, Rowse K, Nugent TE, Blake JW, Tobin T.Studies were undertaken to determine blood levels of furosemide in horses after 0.5- and 1.0-mg/kg doses administered iv. Analyses indicated that the pharmacokinetic parameters were dose independent and best described by a three-compartment open model. The alpha-, beta-, and gamma-phase half-lives of 5.6, 22.3, and 158.5 min, respectively, were observed after the 0.5-mg/kg dose. Similarly, the respective half-lives after the 1.0-mg/kg dose were 5.8, 24.1, and 177.2 min. After a 0.5-mg/kg dose of furosemide, population frequency distributions were evaluated at 1 hr and 4 hr post-drug administra...
You Y, Proctor RM, Vasilko ED, Robinson MA.JWH-250 is a synthetic cannabinoid. Its use is prohibited in equine sport according to the Association of Racing Commissioners International (ARCI) and the Fédération Équestre Internationale (FEI). A doping control method to confirm the presence of four JWH-250 metabolites (JWH-250 4-OH-pentyl, JWH-250 5-OH-pentyl, JWH-250 5-OH-indole, and JWH-250 N-pentanoic acid) in equine urine was developed and validated. Urine samples were treated with acetonitrile and evaporated to concentrate the analytes prior to the analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The chromat...
Clarke CR, MacAllister CG, Burrows GE, Ewing P, Spillers DK, Burrows SL.Pharmacokinetics, CSF penetration, and hematologic effects of oral administration of pyrimethamine were studied after multiple dosing. Pyrimethamine (1 mg/kg of body weight) was administered orally once a day for 10 days to 5 adult horses, and blood samples were collected frequently after the first, fifth, and tenth doses. The CSF samples were obtained by cisternal puncture 4 to 6 hours after administration of the first, third, seventh, and tenth doses. Pyrimethamine concentration in plasma and CSF was quantified by gas chromatography, and plasma concentration-time data were analyzed, using a ...
Jurek KA, Schoonover MJ, Williams MR, Rudra P.To determine the influence of perfusate volume on synovial fluid amikacin concentrations in the joints of the hind limb after standing saphenous intravenous regional limb perfusion (IVRLP). Methods: Randomized crossover design. Methods: Six adult horses. Methods: Saphenous IVRLP was performed in 6 standing horses with 1 g of amikacin diluted with 0.9% NaCl to volumes of 10 ml, 60 ml, and 120 ml. Samples of synovial fluid from the tarsocrural, metatarsophalangeal, and hind limb distal interphalangeal joints were collected at 15 and 30 min after perfusate administration. Concentrations ...
Wilson WD, Baggot JD, Adamson PJ, Hirsh DC, Hietala SK.Sodium cefadroxil was administered as a single intravenous dose (25 mg/kg) to six healthy adult mares. Plasma samples were collected over a 24-h period and cefadroxil concentrations were measured by microbiological assay. The pharmacokinetic behavior of the drug was appropriately described in terms of a one-compartment open model. Values for the major pharmacokinetic terms were: extrapolated initial plasma concentration = 59.2 +/- 15.0 micrograms/ml; half-life = 46 +/- 20 min; apparent volume of distribution = 462 +/- 191 ml/kg; and body clearance = 7.0 +/- 0.6 ml/min.kg. In a subsequent study...
Verde CR, Simpson MI, Frigoli A, Landoni MF.Pharmacokinetic parameters were established for enantiomers of the nonsteroidal anti-inflammatory drug (NSAID) ketoprofen (KTP) administered as the racemic mixture at a dose of 2.2 mg/kg and as separate enantiomers, each at a dose of 1.1 mg/kg to a group of six horses (five mares and one gelding). A four-period cross-over study in a LPS-induced model of acute synovitis was used. After administration of the racemic mixture S(+)KTP was the predominant enantiomer in plasma as well as in synovial fluid. Unidirectional inversion of R(-) to S(+)KTP was demonstrated but the inversion was less marked ...
Nebbia C, Dacasto M, Carletti M.Little is known about the effects of aging on the hepatic drug metabolizing capacity of horses despite the relatively long lifespan characterizing this species. A wide array of cytochrome P450 (CYP)-dependent monooxygenases, carboxylesterases and transferases were assayed in liver microsomes from 50 female horses in an age range between less than 1 year to over 12 years. Rather unexpectedly, both the CYP content and the activity of NADPH cytochrome c reductase rose as a function of age. Accordingly, a general increasing trend was recorded in the rate of the in vitro metabolism of the substrate...
Houghton E, Oxley GA, Moss MS, Evans S.A method is described to confirm the presence of 19-nortestosterone metabolites in urine after the administration of veterinary preparations of this anabolic steroid to horses. The method is based upon the detection, by gas chromatography mass spectrometry or selected ion monitoring, of an isomer of estrane-3,17-diol in the urine.
