Metabolic profile of budesonide after different administration routes and doses

Glucocorticoids are included since 2004 in the World Anti-Doping Agency (WADA) List of Prohibited Substances and Methods, due to their capacity to increase resistance to pain during physical exercise, as well as to induce euphoric and ergogenic effects. The administration of these substances is forbidden “in competition” only and if the case of administration by oral, intravenous, intramuscular or rectal routes. To discriminate between systemic and permitted administration routes, a reporting threshold has been set by the WADA at 30 ng/mL for the urinary concentrations of parent compounds or theirs metabolites. Unfortunately, as already reported by different research groups, this strategy is not always valid. An example is represented by budesonide, whose intake is revealed by the presence in urine of its main phase I metabolite, 16α-hydroxy-prednisolone. Here we have evaluated the excretion profile of budesonide and of its main metabolites after oral and inhaled administration at different therapeutic doses and formulations, with the aim to select the best criteria to discriminate between the abuse and the permitted use of budesonide. Our data show that (1) the urinary level of 16α-hydroxy-prednisolone is higher than the reporting limit also after inhalation; (2) the concentration of the parent compound and of the hydroxylated metabolites exceed the reporting limit only after systemic administration. Moreover our data also show that the ratio between the epimers of the parent compound might be used as additional information in the discrimination between systemic and permitted administration routes