Detection times of clodronic acid in horses with orthopedic disease.
Abstract: Clodronic acid is designated as a controlled medication for competition horses by the International Federation for Equestrian Sports and, according to the International Federation of Horseracing Authorities, clodronic acid is not to be administered to racehorses younger than 3.5 years or within 30 days prior to a race. In this study, 35 horses involved in competition were treated with a single dose of 1.53 mg clodronic acid/kg bodyweight intramuscularly. Plasma samples were obtained before treatment and 10, 20, 30, and 40 days post-administration. Clodronic acid concentrations were measured using a validated method, and the data were fitted using a nonlinear mixed effects model. The estimated depletion half-life of clodronic acid was 10.6 days (inter-individual variability: 17.9%). Age, body weight, sex, disease severity, dose, training days, training, and competition did not significantly impact the depletion half-life. The percentage of horses predicted via simulation to have clodronic acid concentrations below the assay's limit of quantification of 1.0 ng/mL was 93.9% at day 30 and 99.4% at Day 40. This study provides rationale to the equestrian federations and horse racing authorities to reliably establish a detection time for clodronic acid, assisting equine veterinarians in recommending a competition withdrawal time for the horses under their care.
© 2024 GIE LCH. Dechra Veterinary Products and The Author(s). Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.
Publication Date: 2024-06-16 PubMed ID: 38880898DOI: 10.1111/jvp.13453Google 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
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research article presents a study on the detection times of clodronic acid in competition horses undergoing treatment for orthopedic diseases. Clodronic acid usage in these animals is regulated by equestrian authorities, and this study helps to establish a reliable detection window for the medication.
Methodology
- The researchers began with 35 horses, all of whom were being treated for orthopedic conditions and participated in competitions.
- Each horse was given a single intramuscular dose of clodronic acid, which is recognized as a controlled substance for horses in competitions by the International Federation for Equestrian Sports. The International Federation of Horseracing Authorities also advises against administering this medication to racehorses younger than 3.5 years or within 30 days prior to a race.
- Blood samples were taken from the horses at specific times: before the treatment, as well as 10, 20, 30, and 40 days afterward. These samples were used to determine the concentration of clodronic acid in each horse’s system.
Data Analysis
- The measurements were taken using a validated method for quantifying clodronic acid levels, and a nonlinear mixed effects model was used to analyze the data.
- The primary statistic identified in the study was the ‘depletion half-life’ of the clodronic acid, which indicates how long it takes for the concentration of the drug to decrease by half in the horse’s body. This was calculated to be around 10.6 days. However, there was some variability between different individuals, with a standard deviation of 17.9%.
- The researchers also assessed a number of potential factors that might affect the depletion half-life, including the horse’s age, body weight, severity of disease, dose of medication, amount of training, and whether they were actively competing. None of these factors were found to significantly affect the clodronic acid’s depletion half-life.
Results and Implications
- By day 30 post-administration, nearly 94% of the horses were predicted to have clodronic acid levels below the detectable limit of the analysis method used. By day 40, this had increased to almost 100%.
- These findings offer a scientific basis for the guidelines issued by equestrian and horseracing federations regarding the use of clodronic acid. It provides a reliable estimate for how long the drug remains detectable in a horse’s system, which can be used to advise on appropriate withdrawal times before competitions. This is particularly valuable for equine veterinarians caring for competition horses, as it allows them to ensure compliance with the rules while still providing effective medical treatment.
Cite This Article
APA
Seguí Pedrosa B, Dujardin C, Moses B, Thompson C, Sarasola P, Gattacceca F, Loup B, Garcia P, Popot MA, Bailly-Chouriberry L.
(2024).
Detection times of clodronic acid in horses with orthopedic disease.
J Vet Pharmacol Ther.
https://doi.org/10.1111/jvp.13453 Publication
Researcher Affiliations
- Dechra Veterinary Products SLU, Barcelona, Spain.
- Dechra Veterinary Products BV, 's-Hertogenbosch, The Netherlands.
- Dechra Development LLC, Overland Park, Kansas, USA.
- Dechra Development LLC, Overland Park, Kansas, USA.
- Argenta, Hondarribia, Gipuzkoa, Spain.
- Inria-Inserm COMPO Team, Centre Inria Sophia Antipolis - Méditerranée, CRCM, Inserm U1068-CNRS UMR7258, Aix-Marseille University UM105, Marseille, France.
- GIE-LCH, Laboratoire des Courses Hippiques, Verrières le Buisson, France.
- GIE-LCH, Laboratoire des Courses Hippiques, Verrières le Buisson, France.
- GIE-LCH, Laboratoire des Courses Hippiques, Verrières le Buisson, France.
- GIE-LCH, Laboratoire des Courses Hippiques, Verrières le Buisson, France.
References
This article includes 14 references
- Beal SL. Ways to fit a PK model with some data below the quantification limit. Journal of Pharmacokinetics and Pharmacodynamics 28(5), 481–504.
- Dechra Veterinary Products. (2023). Osphos (clodronate injection). http://www.osphos.com/includes/pdf/Dechra‐Osphos‐Legal‐Package‐Insert.pdf
- European Horserace Scientific Liaison Committee. (2021). EHSLC detection times. https://www.ehslc.com/detection‐times
- European Horserace Scientific Liaison Committee. (2023a). EHSLC Advisory Notice: bisphosphonates. https://www.ehslc.com/images/uploads/documents/EHSLC_Advisory_Notice_‐_bisphosphonates.pdf
- European Horserace Scientific Liaison Committee. (2023b). The Science behind this work. https://www.ehslc.com/detection‐times/the‐science‐behind‐this‐work
- European Horserace Scientific Liaison Committee. (2023c). How detection times are agreed. https://www.ehslc.com/detection‐times/how‐dectection‐times‐are‐agreed
- Fédération Équestre Internationale. (2022). FEI list of detection times. https://inside.fei.org/system/files/FEI%20Detection%20Times%202022.pdf
- Fédération Équestre Internationale. (2023). Clean sport for horses – FEI prohibited substances list. https://inside.fei.org/fei/cleansport/ad‐h/prohibited‐list#:~:text=Prohibited%20Substances%20are%20categorised%20as%20follows%3A%20%27Banned%20Substances%27,use%20in%20the%20competition%20horse%20at%20any%20time
- Garcia P, Perot I, Loup B, Balssa F, Jaubert M, Delcourt V, Dujardin C, Popot MA, Bailly‐Chouriberry L. Long‐term detection of clodronate in equine plasma by liquid chromatography‐tandem mass spectrometry. Drug Testing and Analysis 13(8), 1527–1534.
- Hecht M, Veigure R, Couchman L, S Barker CI, Standing JF, Takkis K, Evard H, Johnston A, Herodes K, Leito I, Kipper K. Utilization of data below the analytical limit of quantitation in pharmacokinetic analysis and modeling: Promoting interdisciplinary debate. Bioanalysis 10(15), 1229–1248.
- International Federation of Horseracing Authorities. (2023). International agreement on breeding, racing and wagering. https://www.ifhaonline.org/resources/ifAgreement.pdf
- Knych HK, Finno CJ, Katzman S, Ryan D, McKemie DS, Kass PH, Arthur RM. Clodronate detection and effects on markers of bone resorption are prolonged following a single administration to horses. Equine Veterinary Journal 55(4), 696–706.
- Popot MA, Garcia P, Perot I, Loup B, Balssa F, Jaubert M, Bailly‐Chouriberry L. Determination of clodronic acid in horse plasma by UHPLC‐MS/MS. Proceedings of the 22nd International Conference of Racing Analysts and Veterinarians March 2018, Dubai, United Arab Emirates, 606–611.
- Popot MA, Jacobs M, Garcia P, Loup B, Guyonnet J, Toutain PL, Bailly‐Chouriberry L, Bonnaire Y. Pharmacokinetics of tiludronate in horses: A field population study. Equine Veterinary Journal 50(4), 488–492.
Citations
This article has been cited 0 times.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