Why the racing industry and equestrian disciplines need to implement population pharmacokinetics: To learn, explain, summarize, harmonize, and individualize.
Abstract: Population pharmacokinetics (POP PK) is a powerful pharmacokinetic tool, which measures quantitatively, and explains the variability in drug exposure and drug effect between individuals. POP PK uses an observational (nonexperimental) approach; it is conducted in the target population living in its normal environment (e.g., farm and race-track). The strength of the POP PK approach lies in its greater relevance for the population studied in its different natural environments than experimental studies carried out in more or less biased laboratory conditions. In clinical settings, it is commonly necessary to restrict the number of samples per subject collected for analysis and the derived data cannot be analyzed using traditional individual data analytical methods; rather data are merged and analyzed with an appropriate statistical tool: the nonlinear mixed effect model (NLMEM). POP PK modeling is frequently used with the objective of adjusting drug dosage, and hence drug exposure, not only for the whole population but also for subgroups of animals (e.g., for a given breed, sex, and age). It can also have application at the individual subject level, in the context of precision medicine. For horses, the use of the POP PK/PD model will allow prescribers to estimate an individual Withdrawal Time for a given horse whose treatment they are supervising. Another potential field of application will be meta-analysis of existing data to generate new knowledge on a drug or to collate and synthesize, in an objective and transparent manner, existing data; this will facilitate harmonization of screening limits at an international level.
© 2024 The Author. Drug Testing and Analysis published by John Wiley & Sons Ltd.
Publication Date: 2024-04-29 PubMed ID: 38685692DOI: 10.1002/dta.3706Google Scholar: Lookup
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The study advocates for the wider use of Population Pharmacokinetics (POP PK), a pharmacokinetic tool that accurately measures and explains the varying responses to drug exposure among individuals, in the racing industry and equestrian disciplines. The research positions POP PK as a necessary tool to adjust drug dosage based on individual animals’ characteristics, leading to precision medicine implementations and better withdrawal time estimation for treatment.
Understanding Population Pharmacokinetics
- Population Pharmacokinetics (POP PK) offers a quantitative method to examine and explain the discrepancies in drug exposure and effect between individuals.
- POP PK employs an observational approach, using data from target populations in their natural environments, like farms or race tracks, rather than laboratory conditions.
- The method proves beneficial thanks to its greater relevance for the population studied in different native environments, where it offers more accurate results than lab-experimented studies.
POP PK in Clinical Settings
- In clinical settings, usually there’s a limitation on the number of samples collected per subject for analysis. Traditional individual data analytical methods are therefore not suitable for evaluating the derived data.
- Instead, the collected data are combined and analyzed using a special statistical tool known as the nonlinear mixed effect model (NLMEM).
- The frequent objective of using POP PK modeling is to adjust the drug dosage and hence its exposure, for the entire population and for specific subgroups of animals determined by breed, sex, age, etc.
Applications of POP PK
- Besides its generalized application, POP PK can be useful at a single subject level, helping to usher in precision medicine contextually.
- For horses, specifically, using the POP PK/PD model will enable veterinarians to estimate an individual horse’s Withdrawal Time from treatment more accurately.
- A speculated extension of POP PK is its applicability to meta-analysis of present data. This will not only generate new knowledge on a drug but also objective and transparent synthesis of existing data. On an international level, such an approach can significantly contribute to the harmonization of screening limits.
Cite This Article
APA
Toutain PL.
(2024).
Why the racing industry and equestrian disciplines need to implement population pharmacokinetics: To learn, explain, summarize, harmonize, and individualize.
Drug Test Anal.
https://doi.org/10.1002/dta.3706 Publication
Researcher Affiliations
- INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.
- The Royal Veterinary College, University of London, London, UK.
References
This article includes 34 references
- Aarons L. Population pharmacokinetics: theory and practice.. Br J Clin Pharmacol 1991;32(6):669‐670.
- Sheiner LB, Rosenberg B, Melmon KL. Modelling of individual pharmacokinetics for computer‐aided drug dosage.. Comput Biomed Res 1972;5(5):411‐459.
- U.S. Department of Health and Human Services, Food and Drug Administration. Guidance for Industry. Population Pharmacokinetics.. Department of Health and Human Services, Food and Drug Administration Accessed March 09 2023.
- European Medicine agency. Guideline on reporting the results of population pharmacokinetic analyses.. European Medicine agency CHMP/EWP/185990/06. Accessed March 09 2023.
- Martín‐Jiménez T, Riviere JE. Population pharmacokinetics in veterinary medicine: potential use for therapeutic drug monitoring and prediction of tissue residues.. J Vet Pharmacol Ther 1998;21(3):167‐189.
- Bon C, Toutain PL, Concordet D. Mathematical modeling and simulation in animal health. Part III: using nonlinear mixed‐effects to characterize and quantify variability in drug pharmacokinetics.. J Vet Pharmacol Ther 2018;41(2):171‐183.
- Bonate PL. Pharmacokinetic‐Pharmacodynamic Modeling and Simulation.. Springer 2011.
- Mould D, Upton R. Basic concepts in population modeling, simulation, and model‐based drug development.. CPT: Pharmacomet Syst Pharmacol 2012;1(6):9‐14.
- Mould D, Upton R. Basic concepts in population modeling, simulation, and model‐based drug development‐part 2: introduction to pharmacokinetic modeling methods.. CPT: Pharmacom Syst Pharmacol 2013;2:38.
- Sheiner LB. Learning versus confirming in clinical drug development.. Clin Pharmacol Ther 1997;61(3):275‐291.
- Kuroda T, Minamijima Y, Nomura M. Medication control of flunixin in racing horses: possible detection times using Monte Carlo simulations.. Equine Vet J 2022;54(5):979‐988.
- Van Wijk RC, Imperial MZ, Savic RM, Solans BP. Pharmacokinetic analysis across studies to drive knowledge‐integration: a tutorial on individual patient data meta‐analysis (IPDMA).. CPT Pharmacom Syst Pharma 2023;12(9):1187‐1200.
- EMA/CVMP/VICH/832/1999. VICH GL7 Efficacy of anthelmintics: general 5 requirements (Revision 1) Draft.. EMA/CVMP/VICH/832/1999 Accessed March 10, 2023.
- Tyson RJ, Park CC, Powell JR. Precision dosing priority criteria: drug, disease, and patient population variables.. Front Pharmacol 2020;11:420.
- Toutain PL, Bousquet‐Melou A. Plasma clearance.. J Vet Pharmacol Ther 2004;27(6):415‐425.
- Toutain PL, Lees P. Integration and modelling of pharmacokinetic and pharmacodynamic data to optimize dosage regimens in veterinary medicine.. J Vet Pharmacol Ther 2004;27(6):467‐477.
- Di Paolo A, Luci G. Personalized medicine of monoclonal antibodies in inflammatory bowel disease: pharmacogenetics, therapeutic drug monitoring, and beyond.. Front Pharmacol 2021;11:610806.
- Leven C, Coste A, Mané C. Free and open‐source Posologyr software for Bayesian dose individualization: an extensive validation on simulated data.. Pharmaceutics 2022;14(2):442.
- . EHSLC Detection Times June 2019.. Accessed October 30, 2023.
- Tobin T, Dirikolu L, Brewer K, Hughes CG. A clinician's guide to factors affecting withdrawal times for equine therapeutic medications.. Vet J 2013;198(2):313‐321.
- Toutain P-L. How to extrapolate a withdrawal time from an EHSLC published detection time: a Monte Carlo simulation appraisal: doping control and withdrawal time.. Equine Vet J 2010;42(3):248‐254.
- Toutain P-L, Lassourd V. Pharmacokinetic/Pharmacodynamic assessment of irrelevant drug concentrations in horse plasma or urine for a selection of drugs.. In: Proceedings of the 14th International Conference of Racing Analysts and Veterinarians, Orlando, Florida, USA. R & WNPublication (Newmaket) Limited; 2003:19‐27.
- Mcgree JM, Noble G, Schneiders F. A Bayesian approach for estimating detection times in horses: exploring the pharmacokinetics of a urinary acepromazine metabolite.. J Vet Pharmacol Ther 2013;36(1):31‐42.
- Li M, Gehring R, Lin Z, Riviere J. A framework for meta‐analysis of veterinary drug pharmacokinetic data using mixed effect modeling.. J Pharm Sci 2015;104(4):1230‐1239.
- Toutain PL, Bousquet‐Melou A. Plasma terminal half‐life.. J Vet Pharmacol Ther 2004;27(6):427‐439.
- Courlet P, Buclin T, Biollaz J, Mazzoni I, Rabin O, Guidi M. Model‐based meta‐analysis of salbutamol pharmacokinetics and practical implications for doping control.. CPT Pharm Syst Pharma 2022;11(4):469‐481.
- Lallemand EA, Bousquet‐Mélou A, Chapuis L. Pharmacokinetic–pharmacodynamic cutoff values for benzylpenicillin in horses to support the establishment of clinical breakpoints for benzylpenicillin antimicrobial susceptibility testing in horses.. Front Microbiol 2023;14:1282949.
- Toutain P-L. Veterinary medicines and competition animals: the question of medication versus doping control.. Handb Exp Pharmacol 2010;315‐339.
- European Food Safety Agency. Guidance on Expert Knowledge Elicitation in Food and Feed Safety Risk Assessment.. EFS2 12. Accessed October 30, 2023.
- Lindley DV. Scoring rules and the inevitability of probability.. Int Stat Rev Revue Int de Stat 1982;50(1):1‐11.
- Cheeseman P. In defense of probability.. Proc Ninth Int Joint Conf Artif Intell 1985;85:1002‐1009.
- Bousquet‐Mélou A, Schneider M, El Garch F. Determination of the pharmacokinetic‐pharmacodynamic cut‐off values of marbofloxacin in horses to support the establishment of a clinical breakpoint for antimicrobial susceptibility testing.. Equine Vet J 2021;53(5):1047‐1055.
- Popot MA, Jacobs M, Garcia P. Pharmacokinetics of tiludronate in horses: a field population study.. Equine Vet J 2017;50(4):488‐492.
- Schmidt S, Vozmediano V, Cristofoletti R. Requirements, expectations, challenges and opportunities associated with training the next generation of pharmacometricians.. CPT Pharmacom Syst Pharma 2023;12(7):883‐888.
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