Progress 01/01/06 to 12/31/06
Outputs
Studies conducted in the Equine Performance Lab over the last year have produced valuable new information about ethanol, fluoxetine and fluphenazine in addition to several published reports from studies in previous years including on non-steroidal anti-inflammatory drugs, sildenafil, guanabenz and procaine. Reports from Pennsylvania and Nebraska indicate that ethanol is administered intravenously to horses as a calming agent. This is obviously not an approved practice and our initial studies indicate that transient relaxation and gait alteration can be noted following administration. Fluphenazine and fluoxetine as reported used as well for calming effects. The pharmacokinetics of these drugs was investigated. Fluphenazine caused marked and dangerous alterations in the demeanor of the horses, compulsive behavior and excitation. Studies were curtailed to insure the safety of horses and personnel. Our investigations into the great variation between the commonly available
non-steroidal anti-inflammatory medications in the COX I vs. II inhibition produced published information on alternative methods of detecting the administration of COX inhibitory drugs. The ratio of COX I to COX II inhibition can indicate which drug was administered using an ex vivo analysis on whole blood. The serum concentrations of procaine administered to accomplish regional anesthesia are very low and are comparable to the serum concentrations obtained by the administration of procaine penicillin. We have reported our studies determined that a serum concentration that distinguishes the two sources is non-existent. The effect of sildenafil on the pulmonary arterial pressure is being investigated with the goal of identifying an agent that will reduce arterial pressure. The serum and urine concentrations produced by oral administrations at 2 dose rates were published. Guanabenz, a sympatholytic, anti-hypertensive agent, has been given to horses as a calming agent. From our studies,
we report guanabenz administration decreases heart rate during intense exercise and may increase endurance.
Impacts
The studies undertaken have practical importance in the regulation and control of drug administration to horses in competition, to the safety of horses and handlers, and to medical treatment of horses. The identification of the COX inhibitory characteristics of non-steroidal drugs can lead to safer and more effective drug selection. In addition, for forensic purposes, it may be possible to preliminarily identify the drug being used knowing the COX inhibitory characteristics of the drugs. Knowing the efficacy of sildenafil to alter blood pressure in horses could lead to the development of therapeutic uses for the drug. Fluoxetine and fluphenazine are potential calming agents for horses, but are minimally investigated for pharmacological effects. Fluphenazine causes marked and dangerous alterations in the demeanor of horses. Procaine is a useful added to penicillin g for intramuscular injection, but it is not possible to distinguish procaine administered with penicillin
from procaine administered to anesthetize nerves and block pain from limb injuries of horses in athletic competition. In horses, guanabenz has effects on the heart during intense exercise and may be performance enhancing. Before the drugs become widely used information about dose rates and safely must be known, these studies have augmented the information available.
Publications
- C Cole, K Zientek, N Kuchembuck, D Pirman, Kirsten Wegner, and P Colahan: 2007 Plasma procaine concentrations associated with subcutaneous and intra-articular administation of procaine and intra-articular administration of procaine penicillin to horses. In press to Proceedings of the 16th International Conference of Racing Analysts and Veterinarians, Tokoyo, Japan, 2006.
- P Colahan, K Savage, M Johnson, B Rice, and C Jackson: 2006 The effects of adrenergic suppression induced by guanabenz administration on exercising Thoroughbred horses. In Proceeding of the 7th ICEEP, EVJ Suppl pp 262 to 266.
- N Kuchembuck, P Colahan, Keith Zientek, David Pirman, Kirsten Wegner, Cynthia Cole: 2007 Plasma concentrations and local anesthetic of activity following the subcutaneous administration of procaine to horses. In press AJVR
- P Colahan, C Jackson, B Rice and N Szabo: 2007 Plasma and urine sildenafil and desmethylsildenafil concenrrations and plasma cGMP concentrations associated with oral administration at 1.5 and 5.0 mg.kg bwt to exercise-conditioned thoroughbred horses. In press to Proceedings of the 16th International Conference of Racing Analysts and Veterinarians, Tokoyo, Japan, 2006.
- C Jackson, P Colahan, and B Rice: 2007 Use of a commercially available prostaglandin E2 enzyme-linked immunoassay for NSAID screening in testing laboratories. In press to Proceedings of the 16th International Conference of Racing Analysts and Veterinarians, Tokoyo, Japan, 2006.
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Progress 09/01/00 to 08/31/06
Outputs
Studies conducted in the Equine Performance Lab have produced valuable information about several drugs including several non-steroidal anti-inflammatory drugs, sildenafil, procaine, fluoxetine, fluphenazine, ethanol, erythropoietin, and darbipoetin. There is great variation between the commonly available non-steroidal anti-inflammatory medications in the COX I vs. II inhibition produced. The therapeutic need to reduce inhibition of essential, constitutive COX I and increase inhibition of pro inflammatory COX II can be approached using the data developed. The serum concentrations of procaine administered to accomplish regional anesthesia are very low and are comparable to the serum concentrations obtained by the administration of procaine penicillin. Determination of a concentration level that distinguishes the two sources is ongoing. The effect of sildenafil on the pulmonary arterial pressure is being investigated with the goal of identifying an agent that will reduce
arterial pressure and help prevent EIPH or other disease that may altered by blood pressure. Fluoxetine and fluphenazine are currently being investigated to determine their effects on the horse's sensorium and to lean the pharmacodynamics of the drugs on horses. Administration of fluphenazine to horses can lead to compulsive behavior and excitation. That aspect of that drug could make administration of the rug dangerous to the horse and the personnel handling the horse. Ethanol intravenously can produce a short term calming effect and the elimination time is very short. Erythropoietin and darbepoitin have only insensitive analytic methods that limit the ability to study them. Blood cell parameters are investigated to determine changes caused by hematopoetic stimulation.
Impacts
The studies undertaken have practical importance. The identification of the COX inhibitory characteristics of non-steroidal drugs can lead to safer and more effective drug selection. In addition, for forensic purposes, it may be possible to approximate the drug being used knowing the COX inhibitory characteristics of the drugs. Knowing the efficacy of sildenafil to alter blood pressure in horses could lead to the development of therapeutic uses for the drug. Fluoxetine and fluphenazine are potential calming agents for horses, but are minimally investigated for pharmacological effects. The hematopoetic drugs are dangerous to horses and the study of them is compromised by insensitive analytic techniques. Ethanol is a calming agent of short duration. Before the drugs become widely used information about dose rates and safely must be known.
Publications
- Anderson, D., Kollias-Baker, C., Colahan, P., Keene, R., Lynn, R., and Hepler, D. 2005. Urinary and serum concentration of Diclofenac after topical application to horses. Veterinary Therapeutics, 6(1):57-66.
- Mao, C.-L., Zientek, K., Colahan, P., Kuo, M.-Y., Liou, C.-H., Lee, K.-M., and Chou, C.-C. 2006. Development of an enzyme-linked immunosorbent assay for fentanyl and application of fentanyl anti-body-coated nanoparticles for sample preparation. J Pharmaceutical and Biomedical Analysis 41(4):1332-1341.
- Colahan, P., Savage, K., Tebbett, I., Rice, B., Freshwater, L., and Jackson, C. 2006. The effect of adrenergic suppression induced by guanabenz administration on exercising Thoroughbred horses. Equine Vet. J. Suppl 36 pp 262-266.
- Kuchembuck, N., Colahan, P., Zientek, K., Pirman, D., Wegner, K., Cole, C.: Plasma concentrations and local anesthetic of activity following the subcutaneous administration of procaine to horses. Am J Vet Res. 2007. 68(5):495-500.
- Colahan, P., Jackson, C., Rice, B. and Szabo, N.: Plasma and urine sildenafil and desmethylsildenafil concenrrations and plasma cGMP concentrations associated with oral administration at 1.5 and 5.0 mg.kg bwt to exercise-conditioned thoroughbred horses. In Proceedings of the 16th International Conference of Racing Analysts and Veterinarians, Tokoyo, Japan, 2006. Pp 539-545.
- Savage, K.A., Colahan, P.T., Tebbett, I.R., Rice, B.L., Freshwater, L.L., and Jackson, C.A. 2005. Effects of caffeine on exercise performance of physically fit Thoroughbred. Am J Vet Res 66(4):1-5.
- Colahan, P.T., Johnson, M., Rice, B.L., Jackson, C.A., and Hall, G. 2005. The elimination time of albuterol administered as an inhalant and as an oral syrup to athletically conditioned thoroughbred horses. The Proceeding of the 15th Annual Meeting of Racing Analysts and Veterinarians, Dubai, UAE Pp 340-344.
- Jackson, C., Colahan, P., and Rice, B.: Use of a commercially available prostaglandin E2 enzyme-linked immunoassay for NSAID screening in testing laboratories. In Proceedings of the 16th International Conference of Racing Analysts and Veterinarians, Tokoyo, Japan, 2006 pp 477 - 482.
- Zientek, K., Cole, C., Wegner, K., Kuchembuck, N., Pirman, D. and Colahan, P: Detection of non-permitted agents administered by intra-articular injection to horses. In Proceedings of the 16th International Conference of Racing Analysts and Veterinarians, Tokoyo, Japan, 2006 pp 130-137.
- Cole, C., Zientek, K., Kuchembuck, N., Pirman, D., Wegner,K., and Colahan, P.: Plasma procaine concentrations associated with subcutaneous and intra-articular administration of procaine and intra-articular administration of procaine penicillin to horses. In press to Proceedings of the 16th International Conference of Racing Analysts and Veterinarians, Tokoyo, Japan, 2006 pp 354-359.
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Progress 01/01/05 to 12/31/05
Outputs
Studies conducted in the Equine Performance Lab have produced valuable information about several drugs including several non-steroidal anit-inflammatory drugs, sildenafil, procaine, fluoxetine and fluphenazine. There is great variation between the commonly available non-steroidal anti-inflammatory medications in the COX I vs. II inhibition produced. The therapeutic need to reduce inhibition of essential, constitutive COX I and increase inhibition of pro inflammatory COX II can be approached using the data developed. The serum concentrations of procaine administered to accomplish regional anesthesia are very low and are comparable to the serum concentrations obtained by the administration of procaine penicillin. Determination of a concentration level that distinguishes the two sources is ongoing. The effect of sildenafil on the pulmonary arterial pressure is being investigated with the goal of identifying an agent that will reduce arterial pressure and help prevent
EIPH or other disease that may altered by blood pressure. Fluoxetine and fluphenazine are currently being investigated to determine their effects on the horse's sensorium and to lean the pharmacodynamics of the drugs on horses. Administration of fluphenazine to horses can lead to compulsive behavior and excitation. That aspect of that drug could make administration of the rug dangerous to the horse and the personnel handling the horse.
Impacts
The studies undertaken have practical importance. The identification of the COX inhibitory characteristics of non-steroidal drugs can lead to safer and more effective drug selection. In addition, for forensic purposes, it may be possible to approximate the drug being used knowing the COX inhibitory characteristics of the drugs. Knowing the efficacy of sildenafil to alter blood pressure in horses could lead to the development of therapeutic uses for the drug. Fluoxetine and fluphenazine are potential calming agents for horses, but are minimally investigated for pharmacological effects. Before the drugs become widely used information about dose rates and safely must be known.
Publications
- Savage, K.A., Colahan, P.T., Tebbett, I.R., Rice, B.L., Freshwater, L.L., and Jackson, C.A. 2005. Effects of caffeine on exercise performance of physically fit Thoroughbred. Am J Vet Res 66(4):1-5.
- Colahan, P.T., Johnson, M., Rice, B.L., Jackson, C.A., and Hall, G. 2005. The elimination time of albuterol administered as an inhalant and as an oral syrup to athletically conditioned thoroughbred horses. The Proceeding of the 15th Annual Meeting of Racing Analysts and Veterinarians, Dubai, UAE Pp 340-344.
- Anderson, D., Kollias-Baker, C., Colahan, P., Keene, R., Lynn, R., and Hepler, D. 2005. Urinary and serum concentration of Diclofenac after topical application to horses. Veterinary Therapeutics, 6(1):57-66.
- Mao, C.-L., Zientek, K., Colahan, P., Kuo, M.-Y., Liou, C.-H., Lee, K.-M. and Chou, C.-C. 2006. Development of an enzyme-linked immunosorbent assay for fentanyl and application of fentanyl anti-body-coated nanoparticles for sample preparation. In Press J Pharmaceutical and Biomedical Analysis.
- Colahan, P., Savage, K., Tebbett, I., Rice, B., Freshwater, L., and Jackson, C. 2006. The effect of adrenergic suppression induced by guanabenz administration on exercising Thoroughbred horses. In Press Equine Vet. J.
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Progress 01/01/04 to 12/31/04
Outputs
Ongoing studies of COX II inhibitors indicate that there is great species variation in the COX I vs. II inhibition by agents that are primary COX II inhibitors in humans. In horses, this may mean great variations in efficacy and safety from reported human data. There is the potential that COX II inhibitors may provide analgesia and block inflammation with greater safety to the gastrointestinal tract than do currently used non-steroidal anti-inflammatory agents, but that remains to be demonstrated. Data analysis of sildenafil studies does not yet indicate the effect of that human erectile dysfunction therapeutic on the performance or pulmonary arterial pressure of horses. A pulmonary arterial pressure reducing agent may help alleviate exercised induced pulmonary hemorrhage, a common syndrome in athletic horse that leads to lost performance and early athletic retirement. Ongoing studies of procaine and procaine penicillin indicate that serum concentrations of procaine
maybe of questionable usefulness in distinguishing between the use pf procaine penicillin and procaine local anesthetic. The ability to use procaine penicillin would be of great use in treating common bacterial ailments in athletic horses, however, currently there is no way to distinguish between procaine local anesthesia to hide a musculoskeletal problem and procaine accompanying penicillin.
Impacts
COX II inhibitors have different effects depending on species. The risk of renal damage from the use of these drugs is possible and may be amplified by exercise. The possible reduction of pulmonary arterial pressure may affect performance of exercising horses. The diversion of sildenafil as a performance-altering drug in horses is real and the extent of its effect must be known. The desire by veterinarians to use procaine penicillin g in horses competing in races or sanctioned showing events is prohibited by the potential for procaine to be used as a local anesthesia. A testing regimen that could distinguish the concentration of procaine from antibiotic administration rather than from local anesthesia would aid the treatment of these athletic horses.
Publications
- Xie, H., Colahan, P., and Ott, E., 2004. Electro-acupuncture for the Treatment of Chronic Back Pain in Performance Horses: A Controlled Clinical Trial JAVMA in press.
- Colahan, P., Johnson, M., Rice, B., Jackson, C., and Hall, G. 2004. Determination by ELISA analysis of the elimination time of albuterol administered as and inhalant and as an oral syrup to athletically conditioned Thoroughbred horses subjected to a period of intense exercise. Proceedings of the 15th International Conference of Racing Analysts and Veterinarians, Dubai, UAE in press.
- Savage, K., Colahan, P., Johnson, M., Rice, B., Jackson, C., 2004. Lack of effect of caffeine on selected performance parameters of fit Thoroughbred horses. AJVR in press.
- Colahan, P., Ford, P., Chou, C-C., Johnson, M., Rice, B., and Jackson, C. 2003. The elimination of caffeine origination from human food sources from athletically conditioned Thoroughbred horses as determined by ELISA analysis. DW Hill and WT Hill eds Proceedings of the 14th International Conference of Racing Analysts and Veterinarians, Orlando Florida. R and W Publications LTD Newmarket. pp 308-314.
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Progress 01/01/03 to 12/31/03
Outputs
The effects of a COX II inhibitor on equine renal function was investigated. Those studies are ongoing. The effects of sildenafil on the pulmonary arterial pressure during exercise was investigated and the data is being analysed. The determination of the elimination time of sildenafil from exercising horses is awaiting sample analysis.
Impacts
COX II inhibitors have different effects depending on species. The risk of renal damage from the use of these drugs is possible and may be amplified by exercise. The possible reduction of pulmonary arterial pressure may affect performance of exercising horses. The diversion of sildenafil as a performance altering drug in horses is real and the extent of its effect must be known.
Publications
- Savage K, Colahan P, Johnson M, Jackson C, Tebbett I, Hall G and Rice B. 2003 The effects of caffeine on the performance of intensively exercising Thoroughbred horses. Submitted to JAVMA
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Progress 01/01/02 to 12/31/02
Outputs
We have investigated the pharmacokinetics of sildenafil, guanabenz, and rofecoxib. The samples have been collected for the investigation of sildenafil and rofecoxib. Sildenafil is a peripheral vasoactive agent sold in the human market for the treatment of erectile dysfunction. It is of interest in exercising horses because it has been reported to reduce pulmonary arterial pressure. In horses the reduction of pulmonary arterial pressure maybe helpful in preventing or reducing the severity of exercise induced pulmonary hemorrhage. Refocoxib is a COX-II inhibitor. Inhibition of the COX-II enzyme blocks the inflammatory responses to injury. The method of action is similar to the non-steroidal inflammatory agents commonly used in horses. However, because the method of action is specific to the negative aspects of the inflammatory cascade and metabolic control mechanisms are not affected the COX-II inhibitors may be preferred to the commonly used non-steroidal agents. We
have completed our studies of guanabenz. Guanabenz is an anti-hypertensive drug. It has potential to be used to reduce excitation in horses. Our studies have found that it does appear to have a calming effect in that the heart rate of treated horses was lower even during an incremental exercise stress test. Development and validation of analytical methods to study guanabenz was completed and have been compiled in a thesis to document the study methods. Concurrent studies of the alterations in the genomic upregulation of circulating monocytes and muscle cells caused by intense exercise have been conducted as well. These ongoing studies aim to elucidate the effects of exercise specifically on the cells being investigated to produce pro-inflammatory cytokines.
Impacts
The studies of rofecoxib and sildenafil hold some promise as useful therapeutic agents for common debilitating problems in horses. Guanabenz appears not to have any serious therapeutic role and its use in horses is not recommended.
Publications
- P Colahan, J Bailey, M Johnson, C Chou, and B Rice. 2002. The effect of flunixin meglumine on selected physiological and performance parameters of athletically conditioned Thoroughbred horses subjected to an incremental exercise stress. Veterinary Therapeutics 3:37-48.
- P Colahan, J Bailey, M Johnson, B Rice, C-C Chou, J Cheeks, G Jones, and M Yang. 2002. The effect of a combination of sulfadiazine and pyrimethamine on selected physiological and performance parameters in athletically conditioned Thoroughbred horses during an incremental exercise stress test. Veterinary Therapeutics 3:49-63.
- P Colahan, C Kollias-Baker, C Leutenegger. 2002. Is mRNA transcription for cytokine production in circulating leukocytes affected by initiation of training? 6th Internation Conference Equine Exercise Physiology. Equine Vet J Suppl 34:154-158.
- A Kavazis, E Ott, P Colahan, M Porter, and J Sobota. 2002. The effects of ribose supplementation in exercising horses. 6th Internation Conference Equine Exercise Physiology. Equine Vet J Suppl 34:191-198.
- P Colahan, P Ford, C-C Chou, M Johnson, B Rice and C Jackson. 2002. The elimination of caffeine origination from human food sources from athletically conditioned Thoroughbred horses as determined by ELISA analysis. Accepted for publication in Proceedings of International Conference of Racing Analysts and Veterinarians 14th Annual Meeting, Orlando Florida.
- Chou CC, Chen CL, Rice BL, Colahan PT. 2002. Reduced resident time and pharmacodynamic effects of acepromazine after subclinical multiple dosage in exercised thoroughbreds. J Vet Pharmacol Ther. 25:379-82.
- Savage KA. Development and validation of analytical methods to study the performance-enhancing effects of caffeine and guanabenz in fit thoroughbred horses. Thesis submitted for completion of PhD, University of Florida Dec. 2002.
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Progress 01/01/01 to 12/31/01
Outputs
Drug effects and elimination studies of prednisolone sodium succinate, flunixin meglumine, sulfadiazine and pyrimethamine have been completed and reports are available from the State Division of Pari-mutuel Wagering. Studies of caffeine and albuterol are in the process of data analysis. Data is being collected on the effects and elimination of guanabenz.
Impacts
The data on flunixin meglumine, prednisolone sodium succinate , and sulfadiazine/pyrimethamine made available enables the treatment of horses engaged in pari-mutuel competitions without the risk of drug violations. It also provides information about accurate dosages for veterinarians and gives pari-mutuel regulators information about the urine drug concentrations achieved by therapeutic administrations of these medications.
Publications
- No publications reported this period
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