Administration Studies in Equine Antidoping Research: Designing Scientific Investigations to Effectively Direct Medication Control in Racehorses.
Abstract: Pharmacokinetics is the study of the movement of drug in the body and includes the processes of absorption, distribution, metabolism, and excretion. Pharmacodynamics is the pharmacologic effect of the drug on the body. The pharmacokinetics of a drug determines its pharmacologic effect. Pharmacokinetic studies describe drug concentrations while pharmacodynamics allow for assessment of drug effects. Combined pharmacokinetic/pharmacodynamic studies allow for integration of drug concentrations with pharmacologic effect. Data generated from pharmacokinetic studies can be especially useful in establishing regulatory recommendations, determining appropriate thresholds, screening limits, administrative stand down times, and corresponding detection times. To generate the appropriate information, the following must be considered (1) the test subjects (i.e., number, age, breed, and fitness level), (2) selection of an appropriate dose/route and duration of administration, (3) sample matrix (blood, urine, and hair), (4) time(s) of sample collection, (5) development of an analytical method with appropriate sensitivity, and (6) what analytes to measure (parent and/or metabolite). Pharmacokinetic studies generate drug concentration data that can be used to calculate key pharmacokinetic variables necessary for establishing screening levels and detection times. Pharmacodynamic assessments can aid in understanding the pharmacologic effects of drugs and in correlating drug concentrations to these effects. Various models, including in vivo (whole animal), in vitro, and ex vivo assessments, can be utilized to determine pharmacodynamic effects. Factors to consider in the design of pharmacokinetic studies, basic pharmacokinetic parameters, and examples of pharmacodynamic assessments will be discussed in detail during this tutorial.
© 2025 The Author(s). Drug Testing and Analysis published by John Wiley & Sons Ltd.
Publication Date: 2025-01-29 PubMed ID: 39876751PubMed Central: PMC12401645DOI: 10.1002/dta.3857Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Review
Cite This Article
APA
Knych HK.
(2025).
Administration Studies in Equine Antidoping Research: Designing Scientific Investigations to Effectively Direct Medication Control in Racehorses.
Drug Test Anal, 17(9), 1560-1566.
https://doi.org/10.1002/dta.3857 Publication
Researcher Affiliations
- KL Maddy Equine Analytical Chemistry Lab (Pharmacology Section), School of Veterinary Medicine, University of California, Davis, California, USA.
MeSH Terms
- Animals
- Doping in Sports / prevention & control
- Horses / metabolism
- Substance Abuse Detection / methods
- Substance Abuse Detection / veterinary
- Pharmaceutical Preparations / metabolism
- Pharmaceutical Preparations / administration & dosage
- Research Design
- Pharmacokinetics
Conflict of Interest Statement
The authors declare no conflicts of interest.
References
This article includes 41 references
- Jerzsele A. Comparative Veterinary Pharmacokinetics. in Readings in Advanced Pharmacokinetics ‐ Theory, Methods and Applications (London, UK: IntechOpen, 2012).
- Jensen R C, Fischer J H, Cwik M J. Effect of age and Training Status on Pharmacokinetics of Flunixin Meglumine in Thoroughbreds. American Journal of Veterinary Research 51 (1990): 591–594.
- Hubbell J a E, Sams R A, Schmall L M, Robertson J T, Hinchcliff K W, Muir W W. Pharmacokinetics of Detomidine Administered to Horses at Rest and After Maximal Exercise. Equine Veterinary Journal 41 (2009): 419–422.
- Knych H K, Vale A, Wilson W D, Kass P H, Arthur R M, Jones J H. Pharmacokinetics of Furosemide Administered 4 and 24 Hours Prior to High‐Speed Exercise in Horses. Journal of Veterinary Pharmacology and Therapeutics 41 (2018): 224–229.
- Villarino N F, Lopez C M, Sams R A, Bayly W M. Pharmacokinetics of Furosemide in Thoroughbred Horses Subjected to Supramaximal Treadmill Exercise With and Without Controlled Access to Water. BMC Veterinary Research 15 (2019): 275.
- Niederberger E, Parnham M J. The Impact of Diet and Exercise on Drug Responses. International Journal of Molecular Sciences 22 (2021): 7692.
- van Baak M A. Influence of Exercise on the Pharmacokinetics of Drugs. Clinical Pharmacokinetics 19 (1990): 32–43.
- Novosadová J. The Changes in Hematocrit, Hemoglobin, Plasma Volume and Proteins During and After Different Types of Exercise. European Journal of Applied Physiology 36 (1977): 223–230.
- Dyke T, Hubbell J, Sams R, Hinchcliff K. Hepatic Blood Flow in Horses During the Recuperative Period From Maximal Exercise. American Journal of Veterinary Research 59 (1998): 1476–1480.
- Dyke T M, Sams R A, Hinchcliff K W. Intensity‐Dependent Effects of Acute Submaximal Exercise on the Pharmacokinetics of Bromsulphalein in Horses. American Journal of Veterinary Research 59 (1998): 1481–1487.
- Dyke T M, Sams R A, Hinchcliff K W. Exercise‐Training‐Induced Alterations in Hepatic Function in Mares. Journal of Applied Physiology 85 (1998): 1442–1447.
- Somani S M, Gupta S K, Frank S, Corder C N. Effect of Exercise on Disposition and Pharmacokinetics of Drugs. Drug Development Research 20 (1990): 251–275.
- Yitalo P. Effect of Exercise on Pharmacokinetics. Annals of Medicine 23 (1991): 289–294.
- Gleadhill A, Marlin D, Harris P A, Michell A R. Reduction of Renal Function in Exercising Horses. Equine Veterinary Journal 32 (2000): 509–514.
- Sams R A. Principles of Drug Disposition in the Horse. Veterinary Clinics of North America. Equine Practice 3 (1987): 221–250.
- Moriguchi T, Shimomitsu T, Odagiri Y. Marked Increase in Urinary Bicarbonate and pH Caused by Heavy Muscular Exercise With Dynamic Knee Extension. Tohoku Journal of Experimental Medicine 198 (2002): 31–39.
- Stanley SD, Sams RA, Harkins JD. Frequency Distribution of Post Race Urine pH From Standardbreds Compared With Thoroughbreds: Research and Regulatory Significance. Equine Veterinary Journal 27 (1995): 471–473.
- Houston T, Chay S, Woods WE. Phenylbutazone and Its Metabolites in Plasma and Urine of Thoroughbred Horses: Population Distributions and Effects of Urinary pH. Journal of Veterinary Pharmacology and Therapeutics 8 (1985): 136–149.
- De Marie L, Boshuizen B, Plancke L, De Bruijn M, Delesalle C. Standardized Exercise Tests in Horses: Current Situation and Future Perspectives. Vlaams Diergeneeskundig Tijdschrift 86 (2017): 63–72.
- Firth EC, Nouws JF, Driessens F, Schmaetz P, Peperkamp K, Klein WR. Effect of the Injection Site on the Pharmacokinetics of Procaine Penicillin G in Horses. American Journal of Veterinary Research 47 (1986): 2380–2384.
- Toutain P-L, Reymond N, Laroute V. Pharmacokinetics of Meloxicam in Plasma and Urine of Horses. American Journal of Veterinary Research 65 (2004): 1542–1547.
- Welsh JC, Lees P, Stodulski G, Cambridge H, Foster AP. Influence of Feeding Schedule on the Absorption of Orally Administered Flunixin in the Horse. Equine Veterinary Journal 24, no. S11 (1992): 62–65.
- Maitho TE, Lees P, Taylor JB. Absorption and Pharmacokinetics of Phenylbutazone in Welsh Mountain Ponies. Journal of Veterinary Pharmacology and Therapeutics 9 (1986): 26–39.
- Valentine J. Preanalytical Methodology for Drug Analysis in Biological Fluids. in Drug Fate and Metabolism: Methods and Techniques (NY: Decker, 1983): 151–207.
- Mehta AC. Preanalytical Considerations in Drug Assays in Clinical Pharmacokinetic Studies. Journal of Clinical Pharmacy and Therapeutics 14 (1989): 285–295.
- Stevenson AJ, Weber MP, Todi F, Young L, Beaumier P, Kacew S. Plasma Elimination and Urinary Excretion of Procaine After Administration of Different Products to Standardbred Mares. Equine Veterinary Journal 24 (1992): 118–124.
- Stevenson AJ, Weber MP, Todi F. Determination of Procaine in Equine Plasma and Urine by High-Performance Liquid Chromatography. Journal of Analytical Toxicology 16 (1992): 93–96.
- Ellsworth M, Ruhr LP, Archbald LF. Effect of Heparin and EDTA Anticoagulants on Phenylbutazone Levels in Equine Plasma. Journal of Veterinary Pharmacology and Therapeutics 9 (1986): 227–229.
- Chindavijak B, Fm B, F D S, Mg B. Alteration of the Pharmacokinetics and Metabolism of Propranolol and Antipyrine Elicited by Indwelling Catheters in the Rat. Journal of Pharmacology and Experimental Therapeutics 246 (1988): 1075–1079.
- Toutain PL, Bousquet-Mélou A. Bioavailability and Its Assessment. Journal of Veterinary Pharmacology and Therapeutics 27 (2004): 455–466.
- Toutain PL, Bousquet‐Mélou A. Volumes of Distribution. Journal of Veterinary Pharmacology and Therapeutics 27 (2004): 441–453.
- Toutain PL, Bousquet‐Mélou A. Plasma Clearance. Journal of Veterinary Pharmacology and Therapeutics 27 (2004): 415–425.
- Toutain PL, Lassourd V. Pharmacokinetic/Pharmacodynamic Approach to Assess Irrelevant Plasma or Urine Drug Concentrations in Postcompetition Samples for Drug Control in the Horse. Equine Veterinary Journal 34 (2002): 242–249.
- Toutain P‐L. How to Extrapolate a Withdrawal Time From an EHSLC Published Detection Time: A Monte Carlo Simulation Appraisal. Equine Veterinary Journal 42 (2010): 248–254.
- Martinez M. Bioequivalence Studies. in Comparative Pharmacokinetics, 2nd ed. (Wiley‐Blackwell: Ames, Iowa, 2011): 315–346.
- Soma LR, Uboh CE, Luo Y, Guan F, Moate PJ, Boston RC. Pharmacokinetics of Methylprednisolone Acetate After Intra‐Articular Administration and Its Effect on Endogenous Hydrocortisone and Cortisone Secretion in Horses. American Journal of Veterinary Research 67 (2006): 654–662.
- Toutain PL, Brandon RA, de Pomyers H, Alvinerie M, Baggot JD. Dexamethasone and Prednisolone in the Horse: Pharmacokinetics and Action on the Adrenal Gland. American Journal of Veterinary Research 45 (1984): 1750–1756.
- Mangal D, Uboh CE, Soma LR, Liu Y. Inhibitory Effect of Triamcinolone Acetonide on Synthesis of Inflammatory Mediators in the Equine. European Journal of Pharmacology 736 (2014): 1–9.
- Mangal D, Uboh CE, Soma LR. Analysis of Bioactive Eicosanoids in Equine Plasma by Stable Isotope Dilution Reversed‐Phase Liquid Chromatography/Multiple Reaction Monitoring Mass Spectrometry. Rapid Communications in Mass Spectrometry 25 (2011): 585–598.
- Knych HK, Arthur RM, McKemie DS, Baden R, Oldberg N, Kass PH. Pharmacokinetics of Intravenous Flumetasone and Effects on Plasma Hydrocortisone Concentrations and Inflammatory Mediators in the Horse. Equine Veterinary Journal 51 (2019): 238–245.
- Knych HK, Seminoff K, McKemie DS, Kass PH. Pharmacokinetics, Pharmacodynamics, and Metabolism of Acepromazine Following Intravenous, Oral, and Sublingual Administration to Exercised Thoroughbred Horses. Journal of Veterinary Pharmacology and Therapeutics 41 (2018): 522–535.
Citations
This article has been cited 1 times.- Kuroda T, Knych HK, Noble GK, Minamijima Y, Leung GN, Nomura M, Mizobe F, Ishikawa Y, Kusano K, Toutain PL. A Meta-Analysis of International Flunixin Pharmacokinetics in Horses: Toward Regulatory Harmonization and Individualized Detection Times Using Bayesian Paradigm. Drug Test Anal 2026 Jan;18(1):32-50.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists