Systematic analysis to assess the scientific validity of the international residue limits for caffeine and theophylline in horse‐racing

Abstract

Based on their performance-enhancing potential, caffeine and theophylline are prohibited substances in equine sports. Residues in horses can be caused by wilful application or by unintended uptake of contaminated feed. The International Federation of Horseracing Authorities recently introduced international residue limits (IRLs) to facilitate the discrimination between pharmacological relevant and irrelevant concentrations in doping samples. The objective of this study was to investigate the scientific validity of these IRLs. A systematic analysis was performed to assess the IRLs by different statistical approaches using published pharmacokinetic data. 31 out of 218 potentially relevant publications met the inclusion criteria. Thereby, both IRLs were found to be appropriate for the exclusion of the presence of a relevant pharmacological effect after a wilful application. The IRL of theophylline was also determined to be suitable for the prevention of positive doping tests caused by the ingestion of contaminated feed. In contrast, the IRL of caffeine is not suitable to prevent positive doping test caused by the ingestion of more than 10 mg caffeine per day per horse with contaminated feed. The lack of corresponding regulation for paraxanthine, a major active metabolite of caffeine and theophylline, was recognised as a substantial shortcoming of the current system, rendering both IRLs incomplete.

Challenging the international residue limit concept for feed contaminants in equine doping analytics

“…The values derived by Hertzsch and Richter were almost identical for caffeine (14 ng/ml), but about three times higher for theophylline (225 ng/ml) 3 . The higher irrelevant urine concentration found for theophylline might be due to the relatively low number of studies in the literature and the fact that data from repeated applications of a slightly higher dose (5 mg/kg) were used in the calculation.…”

“…In a paper summarised on p 230 of this issue of Vet Record , Hertzsch and Richter address these issues by analysing published pharmacological data using a combination of statistical methods 3 . They found that the IRL of caffeine (50 ng/ml in urine) is suitable to prevent any pharmacological effect of the substance, but may give rise to positive doping results after oral intake of as little as 10 mg of the substance per day.…”

Anti-Doping-Regeln im Pferdesport und pharmakologische Aspekte der regelkonformen Therapie und Fütterung von Sportpferden

“…Eine Überschreitung des IRL für Koffein ist z. B. bereits ab einer oralen Aufnahme von 10 mg Koffein je Pferd und Tag möglich [37].…”

Simultaneous quantification of caffeine and its main metabolites by gas chromatography mass spectrometry in horse urine

“…Paraxanthine can be detected at the highest level between 1 and 15 h following caffeine administration (Budhraja et al, 2007; Machnik et al, 2017). The lack of corresponding regulation for paraxanthine is a substantial shortcoming in horse racing (Hertzsch & Richter, 2019).…”