Large or Food Animal and Equine Medicine Commons^™

A Toxicology And Clinical Study Of Post Race Epitaxis Associated With Exercise Induced Pulmonary Hemorrhage In Thoroughbred Race Horses At The Racecourse Rinconada, Caracas, Venezuela, Abelardo Morales Briceno, Diana Villoria Leon, Kimberly Brewer, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

The aim of this study was to describe cases of epistaxis associated with post-race Exercise Induced Pulmonary Hemorrhage (EIPH) in Thoroughbred horses at the Hippodrome "La Rinconada", Caracas, Venezuela, through a clinic pathological study. We studied a total of 29 cases of epistaxis post-race in Thoroughbred horses at the Hippodrome La Rinconada, Caracas, Venezuela, which is 2,950 meters above sea level. The study included horses between the ages of 2-5 years, 16 stallions and 13 mares, weighing between 450-510 kg. They underwent a clinical examination, although horses presenting with epistaxis were in an emergency situation. Samples of blood and urine …

Breeding Induced Endometritis In The Mare: The Local Innate Immune Response, Elizabeth Moran Woodward

Theses and Dissertations--Veterinary Science

Uterine inflammation after breeding is considered necessary for the clearance of excess semen and debris from the uterus. A subpopulation of mares fails to clear the inflammation in a timely fashion, and develops a persistent breeding induced endometritis (PBIE). Experiments were preformed to evaluate correlations of PBIE to endometrial quality and age. Mares of advanced age and poor endometrial quality had a higher incidence of PBIE. In addition, mares fluctuated in susceptibility to PBIE from one season to the next. The uterine inflammatory gene expression in susceptible and resistant mares within the first 24 hours after breeding was investigated. The …

Evaluation Of Mass Spectrometric Methods For Detection Of The Anti-Protozoal Drug Imidocarb, A. F. Lehner, J. A. Hitron, J. May, C. Hughes, R. Eisenberg, N. Schwint, D. P. Knowles, P. Timoney, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Imidocarb [N,N'-bis[3-(4,5-dihydro-1H-imidazol-2-yl)phenyl]urea, C₁₉H₂₀N₆O₁, m.w. 348.41] is a symmetrical carbanilide derivative used to treat disease caused by protozoans of the Babesia genus. Imidocarb, however, is also considered capable of suppressing Babesia-specific immune responses, allowing Babesia-positive horses to pass a complement fixation test (CFT) without eliminating the infection. This scenario could enable Babesia-infected horses to pass CFT-based importation tests. It is imperative to unequivocally identify and quantify equine tissue residues of imidocarb by mass spectrometry to address this issue. As a pretext to development of sensitive tissue assays, we have investigated possibilities of mass …

Pyrilamine In The Horse: Detection And Pharmacokinetics Of Pyrilamine And Its Major Urinary Metabolite O-Desmethylpyrilamine, L. Dirikolu, A. F. Lehner, J Daniel Harkins, W. E. Woods, W. Karpiesiuk, R. S. Gates, M. Fisher, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Pyrilamine is an antihistamine used in human and veterinary medicine. As antihistamines produce central nervous system effects in horses, pyrilamine has the potential to affect the performance of racehorses. In the present study, O-desmethylpyrilamine (O-DMP) was observed to be the predominant equine urinary metabolite of pyrilamine. After intravenous (i.v.) administration of pyrilamine (300 mg/horse), serum pyrilamine concentrations declined from about 280 ng/mL at 5 min postdose to about 2.5 ng/mL at 8 h postdose. After oral administration of pyrilamine (300 mg/horse), serum concentrations peaked at about 33 ng/mL at 30 min, falling to <2 ng/mL at 8 h postdose. Pyrilamine was not detected in serum samples at 24 h postdosing by either route. After i.v. injection of pyrilamine (300 mg/horse) O-DMP was recovered at a level of about 20 ̄g/mL at 2 h postdose thereafter declining to about 2 ng/mL at 168 h postdose. After oral administration, the O-DMP recovery peaked at about 12 ̄g/mL at 8 h postdose and declined to <2 ng/mL at 168 h postdose. These results show that pyrilamine is poorly bioavailable orally (18%), and can be detected by sensitive enzyme-linked immunosorbent assay tests in urine for up to 1 week after a single administration. Care should be taken as the data suggest that the withdrawal time for pyrilamine after repeated oral administrations is likely to be at least 1 week or longer.

Detection And Confirmation Of Ractopamine And Its Metabolites In Horse Urine After Paylean® Administration, A. F. Lehner, C. G. Hughes, J Daniel Harkins, C. Nickerson, B. Mollett, L. Dirikolu, Jeffrey M Bosken, Fernanda C. Camargo, J. Boyles, A. Troppmann, W. Karpiesiuk, W. E. Woods, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

We have investigated the detection, confirmation, and metabolism of the beta-adrenergic agonist ractopamine administered as Paylean to the horse. A Testing Components Corporation enzyme-linked imunosorbent assay (ELISA) kit for ractopamine displayed linear response between 1.0 and 100 ng/ml, with an 1-50 of 10 ng/ml, and an effective screening limit of detection of 50 ng/mL. The kit was readily able to detect ractopamine equivalents in unhydrolyzed urine up to 24 h following a 300-mg oral dose. Gas chromatography-mass spectrometry (GC-MS) confirmation comprised glucuronidase treatment, solid-phase extraction, and trimethylsilyl derivatization, with selected-ion monitoring of ractopamine-tris(trimethylsilane) (TMS) m/z 267, 250, 179, and 502 …

A Gc-Ms Method For The Determination Of Isoxsuprine In Biological Fluids Of The Horse Utilizing Electron Impact Ionization, Jeffrey M Bosken, A. F. Lehner, C. G. Hughes, W. E. Woods, F. C. Camargo, J. D. Harkins, J. Boyles, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Isoxsuprine is used to treat navicular disease and other lower-limb problems in the horse. Isoxsuprine is regulated as a class 4 compound by the Association of Racing Commissioners, International (ARCI) and, thus, requires regulatory monitoring. A gas chromatography-mass spectrometry method utilizing electron impact ionization was developed and validated for the quantitation of isoxsuprine in equine plasma or equine urine. The method utilized robotic solid-phase extraction and tri-methyl silyl ether products of derivatization. Products were bis-trimethylsilyl (TMS) isoxsuprine and tris-TMS ritodrine, which released intense quantifier ions m/z 178 for isoxsuprine and m/z 236 for ritodrine that were products of C-C cleavage. …

The Mare Reproductive Loss Syndrome And The Eastern Tent Caterpillar Ii: A Toxicokinetic/Clinical Evaluation And A Proposed Pathogenesis: Septic Penetrating Setae, Thomas Tobin, J. Daniel Harkins, John Ford Roberts, Patricia W. Vanmeter, Tara A. Fuller

Maxwell H. Gluck Equine Research Center Faculty Publications

Reviewing the mare reproductive loss syndrome (MRLS), it is proposed that the fundamental mechanism of this syndrome, which includes early fetal loss, late fetal loss, uveitis, pericarditis, and encephalitis, is tissue penetration by septic barbed setal fragments (septic penetrating setae) from Eastern tent caterpillars (Malacosoma americanum). Once ingested, these barbed setal fragments migrate through moving tissues, followed by rapid hematogenous spread of bacteria, bacterial emboli, and/or septic fragments of setae (septic penetrating setal emboli), collectively referred to as septic materials. Pathogenic bacteria, therefore, enter the horse as hitchhikers on or in the caterpillar setal fragments, and MRLS is caused by …

Development Of A Method For The Detection And Confirmation Of The Alpha-2 Agonist Amitraz And Its Major Metabolite In Horse Urine, A. F. Lehner, C. G. Hughes, W. Karpiesiuk, J Daniel Harkins, L. Dirikolu, Jeffrey M Bosken, Fernanda Camargo, J. Boyles, A. Troppmann, W. E. Woods, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Amitraz (N′-(2,4-dimethylphenyl)-N-[[(2,4-dimethylphenyl)imino] methyl]-N-methyl-methanimidamide) is an alpha-2 adrenergic agonist used in veterinary medicine primarily as a scabicide- or acaricide-type insecticide. As an alpha-2 adrenergic agonist, it also has sedative/tranquilizing properties and is, therefore, listed as an Association of Racing Commissioners International Class 3 Foreign Substance, indicating its potential to influence the outcome of horse races. We identified the principal equine metabolite of amitraz as N-2,4-dimethylphenyl-N′-methylformamidine by electrospray ionization(+)-mass spectrometry and developed a gas chromatographic-mass spectrometric (GC-MS) method for its detection, quantitation, and confirmation in performance horse regulation. The GC-MS method involves derivatization with t-butyldimethylsilyl groups; selected ion monitoring (SIM) of m/z …

The Mare Reproductive Loss Syndrome And The Eastern Tent Caterpillar: A Toxicokinetic/Statistical Analysis With Clinical, Epidemiologic, And Mechanistic Implications, Manu Sebastian, Marie G. Gantz, Thomas Tobin, J. Daniel Harkins, Jeffrey M. Bosken, Charlie Hughes, Lenn R. Harrison, William V. Bernard, Dana L. Richter, Terrence D. Fitzgerald

Maxwell H. Gluck Equine Research Center Faculty Publications

During 2001, central Kentucky experienced acute transient epidemics of early and late fetal losses, pericarditis, and unilateral endophthalmitis, collectively referred to as mare reproductive loss syndrome (MRLS). A toxicokinetic/statistical analysis of experimental and field MRLS data was conducted using accelerated failure time (AFT) analysis of abortions following administration of Eastern tent caterpillars (ETCs; 100 or 50 g/day or 100 g of irradiated caterpillars/day) to late-term pregnant mares. In addition, 2001 late-term fetal loss field data were used in the analysis. Experimental data were fitted by AFT analysis at a high (P < .0001) significance. Times to first abortion (“lag time”) and abortion rates were dose dependent. Lag times decreased and abortion rates increased exponentially with dose. Calculated dose × response data curves allow interpretation of abortion data in terms of “intubated ETC equivalents.” Analysis suggested that field exposure to ETCs in 2001 in central Kentucky commenced on approximately April 27, was initially equivalent to approximately 5 g of intubated ETCs/day, and increased to approximately 30 g/day at the outbreak peak. This analysis accounts for many aspects of the epidemiology, clinical presentations, and manifestations of MRLS. It allows quantitative interpretation of experimental and field MRLS data and has implications for the basic mechanisms underlying MRLS. The results support suggestions that MRLS is caused by exposure to or ingestion of ETCs. The results also show that high levels of ETC exposure produce intense, focused outbreaks of MRLS, closely linked in time and place to dispersing ETCs, as occurred in central Kentucky in 2001. With less intense exposure, lag time is longer and abortions tend to spread out over time and may occur out of phase with ETC exposure, obscuring both diagnosis of this syndrome and the role of the caterpillars.

Clenbuterol In The Horse: Confirmation And Quantitation Of Serum Clenbuterol By Lc-Ms-Ms After Oral And Intratracheal Administration, A. F. Lehner, J Daniel Harkins, W. Karpiesiuk, W. E. Woods, N. E. Robinson, L. Dirikolu, M. Fisher, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Clenbuterol is a β₂ agonist/antagonist bronchodilator, and its identification in post-race samples may lead to sanctions. The objective of this study was to develop a specific and highly sensitive serum quantitation method for clenbuterol that would allow effective regulatory control of this agent in horses. Therefore, clenbuterol-d₉ was synthesized for use as an internal standard, an automated solid-phase extraction method was developed, and both were used in conjunction with a multiple reaction monitoring liquid chromatography-tandem mass spectrometry (LC-MS-MS) method to allow unequivocal identification and quantitation of clenbuterol in 2 mL of serum at concentrations as low as 10 …

Effect Of Amitraz And Xylazine On Some Physiological Variables Of Horses, A. Queiroz-Neto, A. B. Carregaro, G. Zamur, J Daniel Harkins, Thomas Tobin, M. I. Mataqueiro, S. C. Gonçalves

Maxwell H. Gluck Equine Research Center Faculty Publications

The effect of the intravenous injection of amitraz (0.1 mg/kg) to horses on cardiac activity, respiratory rate, intestinal motor activity, rectal temperature, sweating and masticating was evaluated and compared to the effect of intravenous administration of xylazine (1mg/kg, iv) on heart rate, respiratory rate and intestinal activity. Amitraz caused a significant decrease in heart activity, respiratory rate and intestinal movements, but these effects were not as pronounced as those caused by xylazine. Amitraz also caused a significant relaxation of the rectal smooth muscle, and an apparent increase in sweating and in the frequency of horses found masticating hay. Rectal temperature …

Remifentanil In The Horse: Identification And Detection Of Its Major Urinary Metabolite, A. F. Lehner, P. Almeida, J. Jacobs, J Daniel Harkins, W. Karpiesiuk, W. E. Woods, L. Dirikolu, Jeffrey M Bosken, W. G. Carter, J. Boyles, C. Holtz, T. Heller, C. Nattrass, M. Fisher, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Remifentanil (4-methoxycarbonyl-4-[(1-oxopropyl)phyenylamino]-1- piperidinepropionic acid methyl ester) is a μ-opioid receptor agonist with considerable abuse potential in racing horses. The identification of its major equine urinary metabolite, 4-methoxycarbonyl-4-[(1- oxopropyl)phenylamino]-1-piperidinepropionic acid, an ester hydrolysis product of remifentanil is reported. Administration of remifentanil HCl (5 mg, intravenous) produced clear-cut locomotor responses, establishing the clinical efficacy of this dose. ELISA analysis of postadministration urine samples readily detected fentanyl equivalents in these samples. Mass spectrometric analysis, using solid-phase extraction and trimethylsilyl (TMS) derivatization, showed the urine samples contained parent remifentanil in low concentrations, peaking at 1 h. More significantly, a major peak was identified as …

Absence Of Detectable Pharmacological Effects After Oral Administration Of Isoxsuprine, J. Daniel Harkins, G. D. Mundy, S. Stanley, W. E. Woods, R. A. Sams, D. R. Richardson, S. C. Grambow, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

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 deflne the scope and duration of its pharmacological responses after oral administration, 6 horses were dosed with isoxsuprine HCI (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 activity, sweat production, anal muscle tone, core and skin …

An Overview Of The Methylxanthines And Their Regulation In The Horse, J Daniel Harkins, W. Allen Rees, G. D. Mundy, Scott D. Stanley, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Caffiene, theophylline and theobromine are naturally occurring members of the methylxanthine family;pentoxfylline, dyphylline and enprofylline are structurally related synthetic pharmaceuticals. Caffiene has predominantly central nervous system effects, theophylline, dyphylline and enprofylline have predominantly bronchodilator effects, while theobromine is associated with diuretic responses. Pentoxfylline is thought to increase red cell deformability and facillitate blood flow through capillary beds. The methylxanthines are not highly potent agents; they are typically administered in gram doses and they tend to have relatively long half-lives. They remain detectable in plasma and urine for relatively long periods. Similarly, traces of the naturally occurring members of this family …

The Pharmacologic Effects Of Isoxsuprine, J. Daniel Harkins, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Isoxsuprine is a therapeutic medication used to treat navicular disease and other lower limb problems in horses and is one of the more frequently detected therapeutic agents in racing horses. In crossover studies, horses were administered intravenous and oral isoxsuprine to determine the character and duration of pharmacological effects. Following intravenous administration, isoxsuprine significantly increased heart rate, spontaneous activity, and sweat production. There was an apparent, although statistically insignificant, increase in cutaneous blood flow. Skin temperature decreased below control values, and there was a significant decrease in core temperature. Isoxsuprine also reduced smooth muscle tone. In contrast, after oral dosing, …

Frequency Distribution Of Post Race Urine Ph From Standardbreds Compared With Thoroughbreds: Research And Regulatory Significance, S. D. Stanley, R. A. Sams, J Daniel Harkins, G. D. Mundy, J. Boyles, W. E. Woods, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

The concentration of drugs and drug metabolites in urine samples of racing horses is strongly influenced by urine pH(Tobin, 1981), depending on whether the drugs are weak acids or weak bases. Drugs that are weak acids tend to concentrate in besic urine. In contrast, drugs that are weak bases tend to concentrate in acidic urine. These relationships have a well-established theoretical basis (the Henderson-Hasselbalch relationship) and have been demonstrated repeatedly in experimental animals and man (Tobin, 1981). More recently, evidence suggests that these relationships also occur with clinically and forensically significant agents in equine urine (Wood, et al. 1990; Gerken …

Hordenine : Pharmacology, Pharmacokinetics And Behavioural Effects In The Horse, M. Frank, T. J. Weckman, T. Wood, W. E. Woods, Chen L. Tai, Shih-Ling Chang, A. Ewing, J. W. Blake, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Hordenine is an alkaloid occurring naturally in grains, sprouting barley, and certain grasses. It is occasionally found in post race urine samples, and therefore we investigated its pharmacological actions in the horse. Hordenine (2.0 mgkg bodyweight [bwt]) was administered by rapid intravenous (iv) injection to 10 horses. Typically, dosed horses showed a tlehmen response and defecated within 60 secs. All horses showed substantial respiratory distress. Respiratory rates increased about 250 per cent and heart rates were approximately double that of resting values. All animals broke out in a sweat shortly after iv injection, but basal body temperature was not affected. …

The Detection, Pharmacokinetics And Behavioral Effects Of Diisopropylamine Dichloroacetate (Dada) In The Horse: A Preliminary Report, J.-M. Yang, W. E. Woods, T. J. Weckman, T. W. Wood, S.-L. Chang, J. W. Blake, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

1. Drug administration studies using diisopropylamine dichloroacetate (DADA) and diisopropylamine (DIPA) were conducted in Thoroughbred and Standardbred horses to assess physiological effects and develop detection methods.

2. Four horses received 0.08 mg DADA/kg body wt and showed no changes in heart and respiratory rates or body temperature as measured over a 1-hr period after administration. A transient diuretic effect was found to occur in 2 mares dosed with 0.80 mg DADA/kg body wt.

3. A qualitative detection method using thin-layer chromatography was developed to detect DIPA, the major metabolite of DADA in equine urine. A quantitative detection method (lower limit …

Phenylbutazone In The Horse: A Review, Thomas Tobin, S. Chay, S. Kamerling, W. E. Woods, T. J. Weckman, J. W. Blake, P. Lees

Maxwell H. Gluck Equine Research Center Faculty Publications

Phenylbutazone is an acidic, lipophilic, nonsteroidal anti-inflammatory drug (NSAID). It is extensively metabolized in the horse. The metabolites so far identified, oxyphenbutazone, y-hydroxyphenylbutazone and y-hydroxyoxyphenbutazone. account for some 25-30% of administered dose over 24 h. The plasma half-life of phenylbutazone and termination of its pharmacological action are determined primarily by its rate of hepatic metabolism. Phenylbutazone acts by inhibiting the cyclooxygenase enzyme system, which is responsible for synthesis of prostanoids such as PGE?. It appears to act on prostaglalidin-H synthase and prostacyclin synthase, after conversion by prostaglandin-H synthase to reactive intermediates. It markedly reduces prostanoid-dependent swelling, edema, erythema, and hypersensitivity …

Pharmacokinetics And Protein Binding Of Morphine In Horses, Joan Combie, Thomas E. Nugent, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Morphine could be detected in horses dosed with 0.1 mg of drug/kg of body weight for up to 48 hours in blood and 144 hours in urine. This dose of morphine elicited no observ­able effects and is a suggested an­algesic dose. Computer analysis revealed that a 3-compartment open system was the best fitting model with a serum half life of 87.9 minutes and a urine half life of 101.1 minutes. Binding to equine serum proteins was linear over a drug con­centration range of 3.88 x 10-5M to 3.50 x 10-aM and averaged 31.6%. In RBC-partitioning experiments, 78.1 % of the …

Drugs And The Performance Horse, Thomas Tobin

Veterinary Science Books

This book presents an unprecedented account of the actions, effects and consequences of drug use in performance horses. Written for horsemen by a veterinarian and world authority on equine drugs, it deals with all classes, types, and uses of drugs. Professor Tobin describes how the drugs act, how they influence performance, and the problems they may cause. He explains the drug testing process and presents the best information available on the clearance times for drugs in horses. The text is written in plain language and with a touch of humor.

A Review Of The Pharmacology, Pharmacokinetics And Behavioral Effects Of Procaine In Thoroughbred Horses, Thomas Tobin, J. W. Blake

Maxwell H. Gluck Equine Research Center Faculty Publications

Since procaine has both local anaesthetic and central stimulant actions its presence in the blood or urine of racing horses is forbidden. After rapid intravenous injection of procaine HC1 (2.5 mg/Kg) in thoroughbred mares plasma levels of this drug fell rapidly (t 1/2 alpha = 5 min) and then more slowly (t 1/2 beta = 50.2 min). These kinetics were well fitted by a two compartment open model (Model I). This model gave an apparent Vdbeta for procaine in the horse of about 3,500 litres. Since procaine was about 45% bound to equine plasma protein this gives a true Vdbeta …

The Gas-Liquid Chromatograph And The Electron Capture Detection In Equine Drug Testing., J. W. Blake, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Three gas-liquid chromatographic (G.L.C.) procedures discussed have been designed around the four "esses" of detection tests--speed, sensitivity, simplicity, and specificity. These techniques are admirably applicable to the very low plasma drug levels encountered in blood testing under pre-race conditions. The methods are equally applicable to post-race testing procedures, where both blood and urine samples are tested. Drugs can only rarely be detected by the electron capture detector (E.C.D.) without a prior derivatization step, which conveys to the drug(s) high electron affinity. Because of broad applicability, two derivatizing agents, heptafluorobutyric (HFBA) and pentafluorpropionic (PFPA) anhydrides are employed. The three techniques, allowing …