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

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.