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.
Chou CC, Webb AI, Brown MP, Gronwall RR, Vickroy TW.Concentrations of caffeine (CA) and two metabolites were measured simultaneously in venous blood and splenius muscle of adult horses using a semi-automated in vivo microdialysis sampling technique. Dialysates from muscle and jugular vein were collected continuously for 48 h and drug levels were determined by high performance liquid chromatography (HPLC). Following i.v. injection, CA (3 mg/kg) attained a peak blood level of nearly 5400 +/- 600 ng/mL and decreased with a half-life of 15.3 +/- 0.7 h. Pharmacokinetic and statistical comparisons between CA concentrations in jugular dialysates and p...
Nebbia C, Ceppa L, Dacasto M, Nachtmann C, Carletti M.The oxidative metabolism of monensin, an ionophore antibiotic extensively used in veterinary practice as a coccidiostat and a growth promoter, was studied in hepatic microsomal preparations from horses, pigs, broiler chicks, cattle and rats. As assayed by the measurement of the amount of the released formaldehyde, the rate of monensin O-demethylation was nearly of the same order of magnitude in all species, but total monensin metabolism, which was estimated by measuring the rate of substrate disappearance by a high-performance liquid chromatography (HPLC) method, was highest in cattle, interme...
Weiss R, Abel D, Scholtysik G, Straub R, Mevissen M.The effects of 5-hydroxytryptamine (5-HT), HTF 919, a new 5-HT(4) agonist, and the antagonists SB 203-186 (5-HT(4)) and tropisetron (5-HT(3)) on intestinal motility were tested in vitro on isolated preparations of horse ileum and pelvic flexure. Concentration-response curves were created by cumulative application of the agonists with or without preincubation of the antagonists. The 5-HT preparation induced a concentration-dependent contraction in equine ileum and pelvic flexure. The results indicate that 5-HT receptors are present in all parts of equine intestine investigated in this study. Tr...
Dumasia MC, Houghton E, Hyde W, Greulich D, Nelson T, Peterson J.Studies related to the in vivo biotransforrmation and urinary excretion of fenspiride hydrochloride in the horse are described. After oral administration, the drug is metabolised by both phase I functionalisation and phase II conjugation pathways. Following enzymatic deconjugation, fenspiride and its phase I metabolites were isolated from post-administration biofluids using bonded co-polymeric mixed mode solid-phase extraction cartridges to isolate the basic compounds. Following trimethylsilylation (TMS), the parent drug and metabolites were identified by capillary gas chromatography-mass spec...
Dehennin L, Bonnaire Y, Plou P.The dietary supplements 19-norandrostenedione and 19-norandrostenediol are potential metabolic precursors of nandrolone. They are considered by law in the United States as prohormones without proven therapeutic, curative or diagnostic properties, and therefore available as over-the-counter drugs. Oral dosages of 0.1-1 mg/kg body weight were readily absorbed in the equine intestinal tract and thereby led to urinary excretion of drastically increased 5alpha-estrane-3beta,17alpha-diol conjugates, which are known to be final metabolites of nandrolone. The actual rules for detection of illicit nand...
Fuller CJ, Ghosh P, Barr AR.Results from in vitro studies have indicated that calcium pentosan polysulphate (CaPPS) may be of therapeutic value in osteoarthritis (OA) in the horse. However, no controlled clinical trials using this drug in equine OA have yet been reported. If CaPPS is to be developed for such use, the relationship between the proposed i.m. dose of CaPPS to be used and the concentrations of drug attained in plasma and synovial fluid of the target joint should first be established. An investigation was undertaken to determine these concentrations after a single 2 mg/kg i.m. injection of CaPPS. Blood and syn...
Bayly WM, Duvivier DH, Votion D, Vandenput S, Art T, Lekeux P.Six Warmblood horses suffering an acute exacerbation of COPD were tested to investigate whether inhalation of ipratropium bromide (IB) dry powder (2,400 microg) 30 min preexercise would improve their exercise capacity. A cross-over protocol with an inert powder placebo (P) was used. Mechanics of breathing and arterial blood gases were determined before treatment, after treatment but pre-exercise, and during an incremental exercise test. Oxygen consumption (VO2) was also measured before and during exercise, and the time to fatigue recorded. Inhalation of IB reduced total pulmonary resistance (R...
Brumbaugh GW.Drugs undergo extensive evaluation before they are marketed. The occurrence of adverse reactions, however, may be so rare that thousands of patients must receive the drug before reliable data are available. It is necessary that veterinarians be informed about the drugs they use, be able to recognize drug-associated complications, know how to evaluate the patient for evidence of drug-associated toxicity, report adverse effects of drugs to the respective manufacturers, and be prepared to provide medical support and antidotal treatment (if it exists) for a patient if toxicosis occurs.
Kollias-Baker C.Analytic chemistry laboratories responding to the concerns of the industry over drug use and abuse in performance horses should continue to develop more sensitive methods of drug detection. The unwanted result of this increase in sensitivity is the detection of therapeutic medications days to weeks after administration. The adoption of decision or threshold concentrations for residues of nonpermitted medications should allow laboratories to focus their efforts on drugs of abuse in the performance horse industries and permit veterinarians to provide appropriate medical care to these equine athl...
Willis AM, Diehl KA, Hoshaw-Woodard S, Kobayashi I, Vitucci MP, Schmall LM.To determine the effect of 0.005% latanoprost solution on intraocular pressure (IOP) of eyes of clinically normal horses and establish the frequency of adverse effects of drug administration. Methods: 20 adult clinically normal horses. Methods: IOP was recorded (7, 9, and 11 AM; 3, 5, and 7 PM) on days 1 and 2 (baseline), days 3 to 7 (treatment), and days 8 to 9 (follow-up). Latanoprost was administered to 1 randomly assigned eye of each horse every 24 hours during the treatment period, following the 7 AM IOP recording. Pupil size and the presence or absence of conjunctival hyperemia, epiphora...
Jacks S, Giguère S, Gronwall PR, Brown MP, Merritt KA.To determine the pharmacokinetics of azithromycin and its concentration in body fluids and bronchoalveolar lavage cells in foals. Methods: 6 healthy 6- to 10-week-old foals. Methods: Azithromycin (10 mg/kg of body weight) was administered to each foal via i.v. and intragastric (i.g.) routes in a crossover design. After the first i.g. dose, 4 additional i.g. doses were administered at 24-hour intervals. A microbiologic assay was used to measure azithromycin concentrations in serum, peritoneal fluid, synovial fluid, pulmonary epithelial lining fluid (PELF), and bronchoalveolar (BAL) cells. Resul...
Duncan JL, Abbott EM, Arundel JH, Eysker M, Klei TR, Krecek RC, Lyons ET, Reinemeyer C, Slocombe JO.These guidelines have been designed to assist in the planning, operation and interpretation of studies which would serve to assess the efficacy of drugs against internal parasites of horses. Although the term anthelmintic is used in the title and text, these guidelines include studies on drug efficacy against larvae of horse bot flies, Gasterophilus spp., which are non-helminth parasites commonly occurring in the stomach of horses. The advantages, disadvantages and application of critical and controlled tests are presented. Information is also provided on selection of animals, housing, feed, d...
Freeman SL, England GC.A technique of transrectal ultrasonography was developed to investigate the effects of romifidine 80 and 120 microg/kg bwt on intestinal motility in the horse. Motility of the small intestine, caecum and left ventral colon were assessed following injection of romifidine and a saline control, using a blinded, cross-over study design in 6 horses. Measurements were taken at 15, 30, 60, 120, 180 and 240 min after drug administration. There was a slight nonsignificant decrease in motility in the control group over the 4 h study period. Both doses of romifidine produced a marked decrease in gastroin...
Kim JY, Kim SJ, Paeng KJ, Chung BC.A gas chromatographic-mass spectrometric (GC-MS) method for the determination of ketoprofen, a non-steroidal anti-inflammatory drug (NSAID), in horse urine by selected ion monitoring (SIM) mode is described. Urine samples (2 mL) were extracted by liquid-liquid extraction with diethyl ether. The residues were then evaporated, derivatized and injected into the GC-MS system. Validation of the GC-MS method in the SIM mode using flurbiprofen as the internal standard (IS) included linearity studies (10-10 000 ng/mL), recovery (95%) and limit of quantitation (LOQ) (10 ng/mL). The response was linear,...
Suominen MM, Tulamo RM, Anttila MO, Sankari SM, Király K, Lapveteläinen T, Helminen HJ.To evaluate the effects of intra-articular (IA) injections of bufexamac in horses, focusing particularly on the effects of bufexamac on articular cartilage. Methods: 20 Standardbreds. Methods: Horses were randomly allocated into 4 groups consisting of 5 horses each, and 20, 60, or 100 mg of bufexamac or 1 ml of sterile saline (0.9% NaCl) solution (control) was injected into 1 intercarpal joint at weekly intervals for 6 treatments (days 0, 7, 14, 21, 28, and 35). Clinical signs and results of hematologic, serum biochemical, and synovial fluid (SF) analyses and radiography were used to evaluate ...
Latimer FG, Colitz CM, Campbell NB, Papich MG.To determine the pharmacokinetics of fluconazole in horses. Methods: 6 clinically normal adult horses. Methods: Fluconazole (10 mg/kg of body weight) was administered intravenously or orally with 2 weeks between treatments. Plasma fluconazole concentrations were determined prior to and 10, 20, 30, 40, and 60 minutes and 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after administration. A long-term oral dosing regimen was designed in which all horses received a loading dose of fluconazole (14 mg/kg) followed by 5 mg/kg every 24 hours for 10 days. Fluconazole concentrations were determined i...
Gokbulut C, Nolan AM, McKellar QA.The present study was carried out to investigate whether the pharmacokinetics of avermectins or a milbemycin could explain their known or predicted efficacy in the horse. The avermectins, ivermectin (IVM) and doramectin (DRM), and the milbemycin, moxidectin (MXD), were each administered orally to horses at 200 microg/kg bwt. Blood and faecal samples were collected at predetermined times over 80 days (197 days for MXD) and 30 days, respectively, and plasma pharmacokinetics and faecal excretion determined. Maximum plasma concentrations (Cmax) (IVM: 21.4 ng/ml; DRM: 21.3 ng/ml; MXD: 30.1 ng/ml) w...
Hagedorn HW, Meiser H, Zankl H, Schulz R.The tricyclic antidepressant doxepin, representing a 5:1 mixture of trans- and cis-isomers, owns tranquilizing properties. This compound has been associated with illicit medication of racing horses, and therefore should be considered in doping control. Because analysis of doxepin in equine body fluids has not been documented in the literature, a highly sensitive analytical method was developed to individually monitor the doxepin isomers in blood and urine of horses by the use of gas chromatography/mass spectrometry. Following a dose of 1 mg doxepin-HCl/kg intravenously (i.v.), both the isomers...
Schatzman U, Armbruster S, Stucki F, Busato A, Kohler I.The analgesic potency of butorphanol 25 microg/kg bodyweight (BW) and levomethadone 100 microg/kg BW, administered together with detomidine 10 microg/kg BW, was measured in twelve Warmblood horses in a randomized, blinded cross-over study. Detomidine with saline 10 ml 0.9% was used as placebo. The nociceptive threshold was determined using a constant current and a pneumatic pressure model for somatic pair Detomidine alone and in combination with butorphanol or levomethadone caused a significant temporary increase (P < 0.05) of the nociceptive threshold with a maximum effect within 15 min and a...
Fubini SL, Todhunter RJ, Burton-Wurster N, Vernier-Singer M, MacLeod JN.Experimental evidence suggests that recommended dosages of some corticosteroids used clinically as antiinflammatory agents for treating arthropathies damage articular cartilage, but low dosages may be chondroprotective. The purpose of this study was to evaluate how different concentrations of methylprednisolone affect chondrocyte function and viability. Articular cartilage and chondrocytes were obtained from young adult horses, 1.5-3.5 years of age. Corticosteroid-induced changes in collagen expression were studied at the transcriptional level by Northern blot analyses and at the translational...
Tang FP, Leung GN, Wan TS.A capillary electrophoresis-mass spectrometry (CE-MS) method for the analysis of quaternary ammonium drugs in equine urine was developed. Quaternary ammonium drugs were first extracted from equine urine by ion-pair extraction and then analysed by CE-MS in the positive electrospray ionization (ESI) mode. Within 12 min, eight quaternary ammonium drugs, each at 1 ng/mL in horse urine, could be detected. The confirmation of these drugs in urine samples was achieved by capillary electrophoresis tandem mass spectrometry (CE-MS/MS). A direct comparison of this method was made with existing liquid chr...
Takeda A, Tanaka H, Shinohara T, Ohtake I.A sample preparation method for mass chromatographic detection of doping drugs from horse plasma is described. Bond Elut Certify (1 g/6 ml) is used for the extraction of 4 ml of horse plasma. Fractionation is performed with 6 ml of CHCl3-Me2CO (8:2) and 5 ml of 1% TEA-MeOH according to its property. Simple and effective clean-up based on non-aqueous partitioning is adopted to remove co-eluted contaminants in both acid and basic fractions. Two kinds of 1-(N,N-diisopropylamino)-n-alkanes are co-injected with the sample into the GC-MS system for the calculation of the retention index. Total recov...
Haines GR, Brown MP, Gronwall RR, Merritt KA, Baltzley LK.Pharmacokinetics and distribution of orbifloxacin into body fluids and endometrium was studied in 6 mares after intragastric (IG) administration at a single dose rate of 7.5 mg/kg body weight. Orbifloxacin concentrations were serially measured in serum, synovial fluid, peritoneal fluid, urine, cerebrospinal fluid, and endometrial tissues over 24 hours. Minimum inhibitory concentrations of orbifloxacin were determined for 120 equine pathogens over an 11-month period. The mean peak serum concentration (Cmax) was 2.41+/-0.30 microg/mL at 1.5 hours after administration and decreased to 0.17+/-0.01...
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...
Harkins JD, Karpiesiuk W, Lehner A, Woods WE, Dirikolu L, Carter WG, Boyles J, Tobin T.This report evaluates the pharmacological responses, urinary detection and mass spectral confirmation of ropivacaine in horses. Ropivacaine, a potent local anesthetic (LA) recently introduced in human medicine, has an estimated highest no-effect dose (HNED) of about 0.4 mg/site as determined in our abaxial sesamoid block model. Apparent ropivacaine equivalents were detectable by ELISA screening using a mepivacaine ELISA test after administration of clinically effective doses. Mass spectral examination of postadministration urine samples showed no detectable parent ropivacaine, but a compound i...
Gardner SY, Papich MG.The pharmacokinetics of cefepime, a new fourth generation cephalosporin with enhanced antibacterial activity, was examined in neonatal foals and adult dogs. Cefepime was administered intravenously (i.v.) at a dose of 14 mg/kg to five neonatal foals and six adult dogs. Blood samples were collected in both groups of animals and plasma cefepime concentrations measured by reverse-phase high-performance liquid chromatography (HPLC). Cefepime concentrations in both groups of animals were described by a two-compartment pharmacokinetic model with elimination half-lives of 1.65 and 1.09 h for the foal ...
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 ...
Henrikson SL, Rush BR.To determine the onset, magnitude, and duration of bronchodilation after administration of aerosolized salmeterol xinafoate in horses with recurrent airway obstruction. Methods: Randomized controlled study Methods: 6 horses with recurrent airway obstruction. Procedure Horses received aerosolized salmeterol (210 microg) or no treatment, using a crossover design. Salmeterol was administered, using a mask designed for aerosol delivery in horses. Subjective rating of airway obstruction (RAO), maximal change in pleural pressure (deltaPplmax), and pulmonary resistance (RL) were determined at baselin...
Schwarz B, Ihry P.A 26-year-old pony mare (ca. 180 kg bodyweight) was presented as an emergency because it had erroneously received 110 times its standard dose of pergolide (Prascend) per os approximately 4 hours earlier. Clinical examination initially was normal except tachycardia of 52 beats/min. The pony was treated symptomatically with paraffin oil and activated charcoal per nasogastric tube to prevent further systemic absorption and accelerate intestinal excretion of the pergolide. Furthermore, the pony received 400 mg of dopamine antagonist azaperone (Stresnil) intramuscularly (i.m.) followed by 80 mg...
Viljanto M, Hincks P, Hillyer L, Cawley A, Suann C, Noble G, Walker CJ, Parkin MC, Kicman AT, Scarth J.The use of testosterone and its pro-drugs, such as dehydroepiandrosterone (DHEA), is currently regulated in horseracing by the application of international testosterone thresholds. However, additional steroidomic approaches, such as steroid ratios, to distinguish overall adrenal stimulation from drug administrations and an equine biological passport for longitudinal steroid profiling of individual animals could be advantageous in equine doping testing. Thus, DHEA concentrations and related ratios (testosterone [T] to DHEA and DHEA to epitestosterone [E]) were assessed in the reference populati...
Colahan PT, Savage KA, Tebbett IR, Rice BL, Jackson CA, Freshwater L.Adrenergic activity accompanies intense exercise and mediates physiological and metabolic responses to exercise. Guanabenz, an antihypertensive drug marketed for human usage, depresses brain vasomotor and cardioaccelerator centres, blocks peripherally adrenergic neurons and is reportedly used as a calming agent in horses but little is known of its effects in the species. Objective: To determine if guanabenz induces measurable signs of adrenergic suppression on fit Thoroughbred horses undergoing intense exercise. Methods: In a random crossover design, 12 exercise conditioned Thoroughbred horses...
Trim CM, Moore JN, White NA.Dopamine hydrochloride was infused intravenously into six horses anaesthetised with halothane. Three dose rates; 0.5, 2.5 and 5.0 micrograms/kg/min, were evaluated in each horse. The cardiac output was significantly increased at 15 and 30 mins following administration of dopamine at 2.5 and 5.0 micrograms/kg/min. The heart rate, facial artery pressure and pulmonary artery pressure remained unchanged. Total peripheral resistance was significantly decreased at 30 mins with 2.5 micrograms/kg/min and at 15 and 30 mins with 5.0 micrograms/kg/min. No significant change was produced in packed cell vo...
Gokbulut C, Nolan AM, McKellar QA.Oxibendazole (OBZ) was administered to eight horses at an oral dose of 10 mg kg(-1) bodyweight each. Parent OBZ could only be detected in plasma at the 0.5 and 1.0 hours post administration sampling times and the mean maximum plasma concentration was 0.008 microg ml(-1). Parent OBZ was detected in faeces between 12 and 72 hours after administration and the highest dry faecal concentration was detected at 24 hours. An unidentified metabolite was detected in plasma between 0.5 and 72 hours. The unidentified metabolite in the plasma of treated horses corresponded to the second eluted metabolite i...
McKinney AR, Suann CJ, Dunstan AJ, Mulley SL, Ridley DD, Stenhouse AM.The equine phase I and phase II metabolism of the synthetic anabolic steroid stanozolol was investigated following its administration by intramuscular injection to a thoroughbred gelding. The major phase I biotransformations were hydroxylation at C16 and one other site, while phase II metabolism in the form of sulfate and beta-glucuronide conjugation was extensive. An analytical procedure was developed for the detection of stanozolol and its metabolites in equine urine using solid phase extraction, acid solvolysis of phase II conjugates and analysis by positive ion electrospray ionization ion ...
Soma LR, Uboh CE, Rudy JA, Perkowski SZ.Naproxen (+6-methoxy-[alpha-methyl]-2-naphthalene acetic acid) is a nonsteroidal anti-inflammatory drug that is used for the treatment of inflammatory conditions in horses. We developed a model that describes the drug's disposition and renal excretion, including synovial fluid disposition and elimination after IV administration in horses. The plasma disposition, after IV administration of 5 mg/kg of body weight, was described by a two-compartment model; mean +/- SD distribution and elimination half-lives were 1.42 +/- 0.42 and 8.26 +/- 2.56 hours, respectively. Plasma concentration of naproxen...
Czerwinski SL, Lyon AW, Skorobohach B, Léguillette R.Ophthalmic antibiotic therapy in large animals is often used empirically because of the lack of pharmacokinetics studies. The purpose of the study was to determine the pharmacokinetics of topical tobramycin 0.3% ophthalmic solution in the tears of normal horses using an automated immunoassay analysis. Results: The mean tobramycin concentrations in the tears at 5, 10, 15, 30 minutes and 1, 2, 4, 6 hours after administration were 759 (±414), 489 (±237), 346 (±227), 147 (±264), 27.6 (±28.4), 14.8 (±66.6), 6.7 (±18.6), and 23.4 (±73.4) mg/L. Mean tobramycin concentration was maintained abo...
Steel CM, Bolton JR, Preechagoon Y, Charles BG.The purpose of this study was to determine the pharmacokinetics and absolute bioavailability of cisapride after intravenous (i.v.) and intragastric (i.g.) administration in healthy, adult horses. Five animals received single doses of 0.1 mg/kg, 0.2 mg/kg and 0.4 mg/kg cisapride by the i.g. route in an open, randomized fashion on different occasions separated by a washout period of at least 48 h. Four of these horses were also given a single i.v. dose of 0.1 mg/kg cisapride. Jugular venous blood was collected periodically up to 24 h after dosing. Plasma cisapride concentrations were measured by...
Taylor P, Scarth JP, Hillyer LL.Within equine drug surveillance, there is significant interest in analyzing intact phase II conjugates of drugs in urine, but progress has been limited by a lack of reference material. Methods: In this study, in vitro techniques using equine liver fractions were employed to produce glucuronide and sulfate conjugates of stanozolol, 16β-hydroxystanozolol and nandrolone, the glucuronide conjugate of morphine and the glutathione metabolite of chlordinitrobenzene for the first time in equine sports drug surveillance. Results: The glucuronide conjugate of the synthetic progestagen altrenogest was a...
Burrows GE, MacAllister CG, Ewing P, Stair E, Tripp PW.The effects of time and method of administration of rifampin with respect to feeding were evaluated in five mature horses. There was a significant (P less than or equal to 0.05) delay in time of maximum serum concentration and an apparent but not significant decrease in oral absorption when rifampin was given as a top dressing on grain as compared with administration in corn syrup 2 h before or 2 h after feeding. Although there were no differences between administration before or after feeding, administration 2 h prior to feeding was selected as the method of choice for future experiments. The...
Kitzman JV, Wilson RC, Booth NH, Hendricks HL, Bush PB.The pharmacokinetics of 4-aminopyridine (4-AP), a drug capable of antagonizing nondepolarizing neuromuscular blocking drugs, as well as several classes of injectable sedative and anesthetic agents, were studied in 6 intact, awake horses. Plasma samples were assayed for 4-AP over a frequent sampling schedule for 8 hours after IV administration. The plasma 4-AP vs time data best fit a 2-compartment pharmacokinetic model. Distribution half-life was 7.4 minutes, elimination half-life was 259 minutes, volume of the central compartment was 0.89 L/kg, volume of distribution (area) was 1.98 L/kg, volu...
Mendoza FJ, Serrano-Rodriguez JM, Buzon-Cuevas A, Perez-Ecija A.Alternatives to surgical castration are necessary for controlling the sexual behaviour of stallions with breeding potential in training and competition. Flutamide is a potent selective non-steroidal androgen receptor competitive antagonist that has been used in human beings as an anti-androgenic drug. In this study, the pharmacokinetics and bioavailability of flutamide and its main active metabolite, 2-hydroflutamide, were determined in seven healthy mature stallions. Single doses of flutamide (1mg/kg intravenously, 1mg/kg orally in fasted horses, 5mg/kg orally in fasted horses and 5mg/kg oral...
Johansson IM, Kallings P, Hammarlund-Udenaes M.The pharmacokinetics and the effects on treadmill exercise of the anti-inflammatory drug meclofenamic acid were studied in seven Standardbred horses after single intravenous and/or oral doses. The decline in plasma concentration after a single intravenous dose of meclofenamic acid (2.2 mg/kg b.wt) was described by a two-compartment open model. The average elimination half-life was 1.4 h, the apparent volume of distribution 0.14 l/kg and the plasma clearance 0.12 l/h kg. Absorption was the rate-limiting step after oral administration. Non-compartmental analysis showed a mean absorption time of ...
Schutte JG, van den Ingh TS.An 18 year old Friesian mare was treated with griseofulvin for dermatomycosis in the second month of pregnancy. Pregnancy was uneventful and after 331 days a male foal was born. The foal showed bilateral microphthalmia, severe brachygnathia superior, and palatocheiloschisis. The lesions were incompatible with life and the animal was euthanized. As similar lesions have been described in other species associated with griseofulvin administration during pregnancy, and the development of the eyes and facial bones in the horse occurs in the second month of pregnancy, the lesions most likely can be a...
Soraci AL, Tapia O, Garcia J.Flurbirpofen (FBP), a member of the 2-aryl propionate nonsteroidal anti-inflammatory drug class, has potent anti-inflammatory and analgesic properties. The commercial preparation is a racemic mixture of the R(-) and S(+) enantiomers of FBP. In this study, R(-) and S(+) FBP were used to investigate the metabolic chiral inversion. Each enantiomer was administered separately (0.25 mg/kg) and in a racemic mixture (0.5 mg/kg) intravenously to horses. Plasma and synovial concentration of each enantiomer was determined and the disposition of each was analyzed. After intravenous administration of R(-)...
Oberhaus EL, Wilson KM, Camp CM, Sones JL.Sulpiride in vegetable shortening (VS) stimulates prolactin in horses for up to 10 days. Although effective, a pharmaceutical grade vehicle is needed for clinical application of sulpiride in horses. Sucrose acetate isobutyrate (SAIB), a hydrophobic polymer, may be an alternative to VS. Four in vivo experiments assessed the efficacy of SAIB for delivery of sulpiride, estradiol cypionate (ECP), and estradiol benzoate (EB). The first three studies utilized geldings to compare prolactin and luteinizing hormone (LH) concentrations between sulpiride delivered in VS and SAIB, and ECP or EB delivered ...
Pedersoli WM, Belmonte A, Purohit RC, Ravis WR.The pharmacokinetics of gentamicin were studied in six healthy mature horses of mixed breeding and of both sexes. A parenteral preparation of gentamicin sulfate (5% aqueous solution) was administered rapidly (IV) at the dosage level of 5 mg/kg of body weight. Venous blood samples were taken at 0 (base line), 0.083, 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, and 120 hours after gentamicin administration. Serum gentamicin was measured by a radioimmunoassay technique. The gentamicin concentration data was fitted to a one- and two-compartment open model with first-order elimination from ...
Afonso T, Giguère S, Rapoport G, Berghaus LJ, Barton MH, Coleman AE.Angiotensin-converting enzyme (ACE) inhibitors are used in horses with cardiovascular disorders despite the paucity of available data regarding their efficacy. Objective: The degree of serum ACE inhibition varies considerably between drugs. Methods: Eight healthy adult horses. Methods: Randomized prospective study. Horses were fasted overnight prior to receiving one of 4 ACE inhibitors intragastrically, administered at one of 2 dosages, using a randomized Latin square design (benazepril: 0.5 and 0.25 mg/kg; ramipril: 0.3 and 0.1 mg/kg; quinapril: 0.25 and 0.125 mg/kg; perindopril: 0.1 and 0.05...
Gehlen H, Fisch J, Merle R, Trachsel DS.Pituitary pars intermedia dysfunction (PPID), a neurodegenerative disease leading to reduced dopamine production, is a common disease in aged horses. The treatment is based on administration of the dopamine agonist pergolide. This drug has been related to valvular fibrosis in humans, but the cardiovascular effect of this drug has not yet been investigated in horses. Objective: To determine whether pergolide induces valvular disease in horses or affects the cardiac function. Methods: Standard, tissue Doppler (TDE) and two-dimensional speckle tracking (STE) echocardiography were performed in hor...
Sams RA, Gerken DF, Ashcraft SM.The respiratory stimulant prethcamide is a mixture of equal parts of crotethamide and cropropamide. A specific and sensitive gas chromatographic method for the determination of crotethamide and cropropamide in horse plasma and urine is described. Both components of prethcamide were extracted from plasma and urine into dichloromethane. The extracts were analyzed by capillary gas chromatography with thermionic detection in the nitrogen-specific detection mode. The lower limits of quantitation were 4.0 ng ml-1 of plasma and 10.0 ng ml-1 of urine. Calibration curves were linear from 2.0-100 ng ml-...
Wasfi IA, Abdel Hadi AA, Elghazali M, Alkateeri NA, Hussain MM, Hamid AM.The pharmacokinetics of diphenhydramine (DPHM) was compared in camels (n = 8) and horses (n = 6) following intravenous (i.v.) administration of a dose of 0.625 mg/kg body weight. In addition, the metabolism and urinary detection time of DPHM was evaluated in camels. The data obtained (median and range in brackets) in camels and horses, respectively, were as follows. The terminal elimination half lives (h) were 1.58 (1.13-2.58) and 6.11 (4.80-14.1), and the total body clearances (L/h per kg) were 1.42 (1.13-1.74) and 0.79 (0.66-0.90). The volumes of distribution at steady state (L/kg) were 2.38...
Foster AP, Cunningham FM, Andrews MJ, Lees P.The effects of the selective platelet activating factor (PAF) receptor antagonist WEB 2170 on PAF-induced responses in equine cells and tissues have been examined and compared with those of WEB 2086. In initial experiments WEB 2170 was shown to inhibit in vitro platelet aggregation in a dose-dependent, competitive reversible manner (pA2 = 7.21). Co-administration of the antagonists with either PAF or histamine also inhibited PAF, but not histamine, induced wheal formation and PAF-induced neutrophil accumulation in vivo in equine skin. Intravenous (i.v.) administration of both drugs at a dose o...
Silva GB, De La Côrte FD, Brass KE, Palma HE, Gallio M, Cantarelli C, Bertolin K, Krause A, Wergutz J, Fontanari Krause LM, Antoniazzi AQ.Chondrocyte health is altered when exposed to local anesthetics, raising concerns as to the long-term effects of local anesthetics intra-articularly for diagnosis and analgesia. To investigate the drug with the lowest toxic potential, the effect of ropivacaine and mepivacaine on chondrocytes was evaluated. Articular cartilage from normal metacarpophalangeal joints of five equine cadaver specimens was used to establish chondrocyte cultures. Following seven days, chondrocytes were exposed to standard culture medium (DMEM), ropivacaine 7.5 mg/ml (ROP7.5), ropivacaine 10 mg/ml (ROP10), mepivacaine...
Delbeke FT, Debackere M, Desmet N, Stevens M.Concentrations of the potent diuretic bumetanide were determined by a sensitive high performance liquid chromatographic procedure in plasma and urine from horses following intravenous and intramuscular administration of a dose rate of 15 micrograms/kg. The elimination half-life was found to be 6.3 min, the volume of distribution at steady state 68 ml/kg and the total plasma clearance 10.9 ml/min/kg. The onset of diuresis occurred within 15 min and diuresis was no longer apparent 1 h after i.v. administration. Given by the intramuscular (i.m.) route, bumetanide was rapidly absorbed; bioavailabi...
Vudathala D, Murphy L.A simple and highly sensitive LC/MS method was developed for the simultaneous determination of six ionophores--lasalocid, monensin, laidlomycin, maduramycin, salinomycin, and narasin--in feed. The procedure involved extraction of 1 g of feed with 4 mL of methanol-water (9 + 1, v/v) by shaking on a platform shaker for 45 min. After centrifugation, the extracts were diluted with methanol-water (75 + 25, v/v) and analyzed without any cleanup. The analysis was performed on a Betasil C18 column (150 x 4.6 mm id, 5 pm particle size) connected to an LC/MS system operated in the atmospheric pressure c...
Smith CM, Steffey EP, Baggot JD, Dunlop CI, Farver TB.Inhalation anesthetics decrease the clearance of some drugs that are eliminated by renal excretion. The purpose of the study reported here was to investigate the effects of halothane anesthesia on the pharmacokinetics and urinary excretion of gentamicin sulfate, using the horse as a model. Using a crossover design, pharmacokinetic values after a single IV dose of gentamicin (4 mg/kg) were compared in halothane-anesthetized and unanesthetized horses. Compared with unanesthetized horses, the anesthetized horses had significant decreases in total body clearance (P less than 0.01) and apparent vol...
Buntenkötter K, Osmers M, Schenk I, Schänzer W, Machnik M, Düe M, Kietzmann M.Although acetylsalicylic acid (ASA) is not frequently used as a therapeutic agent in horses, its metabolite SA is of special interest in equestrianism since it is a natural component of many plants used as horse feed. This led to the establishment of thresholds by horse sport organizations for SA in urine and plasma. The aim of this study was to investigate plasma and urine concentrations of salicylic acid (SA) after oral administration of three different single dosages (12.5 mg/kg, 25 mg/kg and 50 mg/kg) of acetylsalicylic acid (ASA) to eight horses in a cross-over designed study. Results:...
McGorum BC, Nicholas DR, Foster AP, Shaw DJ, Pirie RS.Bronchodilators are frequently used to attenuate airway obstruction in equine heaves (or recurrent airway obstruction). This study evaluated the selective (M(3) and M(1)) muscarinic antagonist revatropate, which offers potential advantages over non-specific antimuscarinic agents such as ipratropium. Protocol 1 assessed the response to inhaled revatropate (1, 2 and 7 mg) using a blinded, negative (inhaled saline) and positive (inhaled ipratropium bromide; 0.3, 0.7 and 2mg) controlled, dose escalation study, with six heaves horses. The lowest doses of revatropate and ipratropium induced a rapid ...
Byars TD, Greene CE, Kemp DT.Warfarin-induced anticoagulation and reversal of the induced anticoagulation by vitamin K1 were evaluated in 4 mature horses. Each horse was given warfarin IV until the prothrombin (PT) time was prolonged by approximately 1.5 times the predosing base-line value. In experiment 1, we evaluated the time required for PT to return to the predosing value (PT reversal time) after warfarin administration was discontinued. Between each experiment, a 1-week rest period was allowed. In experiment 2, two doses of vitamin K1 (100 mg/dose) were administered IM 6 hours apart, and the PT was monitored hourly ...
