Studies of glucocorticoids after oral administration: evaluation of reporting levels and washout periods

Code: T20M03RV

Recent research has demonstrated that the criterion of discrimination between allowed and prohibited administrations of GCs needs to be compound specific. For some GCs, largely detected in doping controls, no sufficient data is available, and the objective of this project is to perform excretion studies with these GCs to generate the data needed to define the reporting levels and the washout periods.

The project will be focused on dexamethasone (DEX), methylprednisolone (MP) and deflazacort (DEF).

The research will be focused on the following specific objectives:

• To perform excretion studies of DEX, MP and DEF with administration of one single oral dose. For DEX, multiple oral doses will be also studied.
• To measure concentrations in urine of the parent compounds and the main metabolite in case of DEF, to evaluate the reporting lebels and washout periods.
• To measure concentrations of the compounds and cortisol in plasma, to evalulate the concordance of the urinary reporting levels and washout periods proposed with plasma concentrations of the active drug and the systemic effect

Main findings

Glucocorticoids (GCs) are prohibited in-competition by all injectable routes (including intraarticular and periarticular routes) in addition to oral and rectal administrations. In out-ofcompetition periods, there is no restriction of use. Since most GCs are marketed in different administration forms, the distinction between administration routes is needed to ensure safe treatments by allowed administration routes and to detect the use of prohibited administration routes during competitions. The regulations of GCs in sports were revisited in 2022, and new criteria were established for some of the compounds. In the present study, the discrimination criteria was evaluated for three GCs: dexamethasone (DEX), methylprednisolone (MP) and deflazacort (DEF).

Five clinical studies which involved oral administration of GCs to healthy volunteers were performed: single oral dose of DEX (4 mg, n=8), multiple oral dose of DEX (2mg/12h/5 days, n=8), single oral dose of MP (12 mg, n=8), multiple oral dose of MP (12 mg/3 days, n=8) and single oral dose of DEF (30 mg, n=8). Urine and plasma samples were collected before, during and after the treatments, and both the urinary and plasmatic excretion profiles of each GCs and their metabolites were evaluated using liquid chromatography-tandem mass spectrometry. Overall, the results of the project demonstrate that the minimum reporting levels (MRL) of 60 ng/mL for DEX, 30 ng/mL of MP and 30 ng/mL of desacetyldeflazacort (DEF metabolite) are suitable to detect oral administration of the compounds and the washout-period of 3 days for oral administration is also adequate for these GCs. Results obtained in this project provide additional data that supports that criteria based on substance-specific MRL improve the discrimination between prohibited and permitted use of GCS in sports.