Pharmacokinetic/pharmacodynamic approach to assess irrelevant plasma or urine drug concentrations in postcompetition samples for drug control in the horse.
Abstract: The current performance of analytical techniques used for drug control in horses lead the Regulatory Authorities to decide whether trace levels of drugs legitimately used for therapeutic medication should or should not be reported. Here, we propose a well-ordered and nonexperimental pharmacokinetic/pharmacodynamic approach for the determination of irrelevant drug plasma (IPC) and urine concentrations (IUC). The published plasma clearance is used to transform an effective (marketed) dose into an effective concentration (EPC). EPC is transformed into an IPC by applying a safety factor (SF). This method is based on several assumptions (eg, drug effects reversibly driven by plasma concentration, linearity of drug disposition). The suitability of the computed IPC and IUC can be checked by calculating the residual amount of drug at IPC and computing a minimal drug withdrawal time. It is concluded that controlling the drug effect (using drug or any analyte concentration as a marker) rather than the drug exposure will be more demanding and also makes urine a less than ideal matrix.
Publication Date: 2002-07-11 PubMed ID: 12108741DOI: 10.2746/042516402776185985Google Scholar: Lookup
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- Journal Article
Summary
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This research paper proposes a method to identify insignificant drug concentrations in horse plasma and urine during post-competition tests, which can help authorities decide whether or not to report nominal traces of therapeutic drugs. The approach combines the principles of pharmacokinetics and pharmacodynamics, and includes calculating the minimal drug withdrawal time to verify the results.
Introduction and Method Proposal
- The authors note that current techniques for controlling drug use in horses often lead to detection of trace levels of drugs, which were legitimately used for therapeutic purposes.
- This study aims to establish a systematic approach that can determine ‘irrelevant’ drug plasma concentrations (IPC) and urine concentrations (IUC).
- This proposed method exploits the principles of pharmacokinetics, the study of how drugs move through the body, and pharmacodynamics, the study of the biochemical and physiological effects of drugs and their mechanisms of action.
Method Execution
- The method starts with using the published plasma clearance rate to convert a typical effective dose of a drug into an effective plasma concentration (EPC).
- Next, a safety factor (SF) is applied to the EPC to derive the IPC. This safety factor seeks to account for any uncertainties or variables not considered within the simpler conversion.
- The entire method rests on certain assumptions, such as the drug effects being reversibly driven by plasma concentration and a linear correlation of drug disposition.
- The suitability and accuracy of the IPC and IUC calculated can be verified by determining the residual drug amount remaining at IPC and calculating a minimum drug withdrawal time.
Conclusion and Implications
- The researchers conclude that monitoring the drug effect (using drug or any analyte concentration as a marker) rather than the mere exposure to the drug could be more rigorous and demanding.
- They also highlight that owing to this, urine might not be the ideal matrix for such testing and analysis.
- This discussion is significant to regulatory authorities as it may influence whether or not trace levels of legitimate therapeutic drugs should be reported in competition horses.
Cite This Article
APA
Toutain PL, Lassourd V.
(2002).
Pharmacokinetic/pharmacodynamic approach to assess irrelevant plasma or urine drug concentrations in postcompetition samples for drug control in the horse.
Equine Vet J, 34(3), 242-249.
https://doi.org/10.2746/042516402776185985 Publication
Researcher Affiliations
- UMR 181 INRA/ENVT Physiopathologie et Toxicologie Expérimentales, Ecole Nationale Vétérinaire de Toulouse, France.
MeSH Terms
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / blood
- Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
- Anti-Inflammatory Agents, Non-Steroidal / urine
- Doping in Sports
- Drug Monitoring / methods
- Drug Monitoring / veterinary
- Drug Residues / analysis
- Drug Residues / pharmacokinetics
- Drug Residues / pharmacology
- Horses / blood
- Horses / urine
- Metabolic Clearance Rate
- Motor Activity / drug effects
- Phenylbutazone / blood
- Phenylbutazone / pharmacokinetics
- Phenylbutazone / urine
- Physical Conditioning, Animal / methods
- Physical Conditioning, Animal / physiology
- Safety
- Veterinary Drugs / blood
- Veterinary Drugs / urine
Citations
This article has been cited 12 times.- Eichler F, Poźniak B, Machnik M, Schenk I, Wingender A, Baudisch N, Thevis M, Bäumer W, Lischer C, Ehrle A. Pharmacokinetic modelling of orally administered cannabidiol and implications for medication control in horses. Front Vet Sci 2023;10:1234551.
- Brewer K, Machin J, Maylin G, Fenger C, Morales-Briceño A, Tobin T. Gabapentin, a human therapeutic medication and an environmental substance transferring at trace levels to horses: a case report. Ir Vet J 2022 Oct 4;75(1):19.
- Kuroda T, Minamijima Y, Nomura M, Yamashita S, Yamada M, Nagata S, Mita H, Tamura N, Fukuda K, Kuwano A, Kusano K, Toutain PL, Sato F. Medication control of flunixin in racing horses: Possible detection times using Monte Carlo simulations. Equine Vet J 2022 Sep;54(5):979-988.
- Nixon E, Mays TP, Routh PA, Yeatts JL, Fajt VR, Hairgrove T, Baynes RE. Plasma, urine and tissue concentrations of Flunixin and Meloxicam in Pigs. BMC Vet Res 2020 Sep 16;16(1):340.
- Ekstrand C, Bondesson U, Giving E, Hedeland M, Ingvast-Larsson C, Jacobsen S, Löfgren M, Moen L, Rhodin M, Saetra T, Ranheim B. Disposition and effect of intra-articularly administered dexamethasone on lipopolysaccharide induced equine synovitis. Acta Vet Scand 2019 Jun 20;61(1):28.
- Axmann S, Hummel K, Nöbauer K, Razzazi-Fazeli E, Zitterl-Eglseer K. Pharmacokinetics of harpagoside in horses after intragastric administration of a Devil's claw (Harpagophytum procumbens) extract. J Vet Pharmacol Ther 2019 Jan;42(1):37-44.
- Buntenkötter K, Osmers M, Schenk I, Schänzer W, Machnik M, Düe M, Kietzmann M. Pharmacokinetics and in vitro efficacy of salicylic acid after oral administration of acetylsalicylic acid in horses. BMC Vet Res 2017 Jan 19;13(1):28.
- Shibany KA, Tötemeyer S, Pratt SL, Paine SW. Equine hepatocytes: isolation, cryopreservation, and applications to in vitro drug metabolism studies. Pharmacol Res Perspect 2016 Oct;4(5):e00268.
- Lin Z, Vahl CI, Riviere JE. Human Food Safety Implications of Variation in Food Animal Drug Metabolism. Sci Rep 2016 Jun 15;6:27907.
- 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.
- Olakojo TA, Akinniyi OO, Dansu EO, Adeoye AO, Adah O, Nwufoh OC, Adeoye BO, Oridupa OA, Saba AB. Misconceptions and misuse: assessing horse caregivers' knowledge, attitudes, and practices regarding dexamethasone use in Ibadan, Nigeria. J Equine Sci 2025;36(3):103-113.
- Knych HK. Administration Studies in Equine Antidoping Research: Designing Scientific Investigations to Effectively Direct Medication Control in Racehorses. Drug Test Anal 2025 Sep;17(9):1560-1566.
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