Urinary excretion patterns and potential risks of beta‐blocker ophthalmic drops in sports

Abstract

Beta-blockers have been prohibited by the World Anti-Doping Agency (WADA) in certain sports, but insufficient research data make it difficult to distinguish between therapeutic uses or misuses. This study aimed at investigating the urinary excretion pattern following beta-blocker ophthalmic drops and the potential risk of constituting an adverse analytical finding (AAF) in sports. Prescribed timolol and carteolol ophthalmic drops were used in healthy participants and glaucoma patients. The urine samples were then collected to investigate the urinary excretion pattern following acute and chronic administration of the above beta-blocker ophthalmic drops. The liquid chromatograph-tandem mass spectrometry method was applied for measuring urinary beta-blockers. Our results demonstrated that the levels of both urinary timolol and carteolol exceeded the minimum reporting levels (MRL) following acute and chronic administration. The highest levels of urinary timolol and carteolol observed in the present study were 255.7 and 923.8 ng/ml, respectively. Regarding the acute administration of timolol ophthalmic drop, 26.19 (11/42) of urine samples were detected with timolol higher than the MRL in timed and random sampling. In contrast, the acute administration of carteolol ophthalmic drops made the carteolol levels higher than the MRL among most urine samples. On the other hand, 36.36% (4/11) of urine samples were detected with beta-blockers higher than the MRL during the chronic administration of timolol and carteolol ophthalmic drops. In the context of receiving ophthalmic beta-blocker medications, the present study has highlighted the potential risk of constituting an AAF in specific sports and suggests strengthening athletes' awareness of therapeutic use exemptions.

Annual banned‐substance review 16th edition—Analytical approaches in human sports drug testing 2022/2023

“…Concerning beta‐receptor blocking agents (beta‐blockers), Lin et al investigated the urinary elimination profile of timolol and carteolol after acute as well as chronic ophthalmic use 115 . With acute and chronic dosages of at least 500 μg of timolol maleate/day and 2 mg of carteolol hydrochloride/day via eyedrop solution application, urinary concentrations of the target analytes exceeding the MRL of 50 ng/mL 145 were observed.…”