Urinary excretion profile of prednisolone and prednisone after rectal administration: Significance in antidoping analysis

Abstract

The rectal administration of glucocorticoids, as well as any injectable, and oral ones, is currently prohibited by the World Anti-Doping Agency when occurs "in competition." A reporting level of 100 ng/ml for prednisolone and 300 ng/ml for prednisone was established to discriminate the allowed and the prohibited administration. Here, the urinary excretion profiles of prednisone and prednisolone were evaluated in five volunteers in therapy with glucocorticoid-based rectal formulations containing prednisone or prednisolone caproate. The urinary levels of the excreted target compounds were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) following the procedure validated and currently in use in our laboratory to detect and quantitate glucocorticoids in urine. Predictably, the excretion trend of the analytes of interest were generally comparable with those obtained after oral administration, even if the excretion profile showed a broad interindividual variability, with the absorption rate and the systemic bioavailability after rectal administration being strongly influenced by the type of formulations (suppository or rectal cream, in our case) as well as the physiological conditions of the absorption area. Results showed that the target compounds were detectable for at least 30 h after drug administration. After suppository administration, prednisolone levels reached the maximum after 3 h from drug administration and then dropped below the reporting level after 15-21 h; prednisone reached the maximum after 3 h from drug administration, and then dropped below the reporting level after 12-15 h. After cream administration, both prednisone and prednisolone levels remained in a concentration below the reporting level throughout the entire monitored period.

Annual banned‐substance review—Analytical approaches in human sports drug testing 2021/2022–

“…Also, glucuronic acid conjugation was observed for most hydroxylated (cream). 90 The reporting levels of 300 and 100 ng/ml, respectively, were exceeded up to 21 h after application, which is an important information in case this less common therapy is indicated and to avoid an inadvertent ADRV.…”

“…To study the elimination profiles of rectal administrations of glucocorticoids, which are also prohibited, Iannella et al investigated prednisone and prednisolone applied as either suppository or cream formulation and monitored five patients receiving either 100 mg of prednisone (suppository) or 5–15 mg of prednisolone caproate (cream) 90 . The reporting levels of 300 and 100 ng/ml, respectively, were exceeded up to 21 h after application, which is an important information in case this less common therapy is indicated and to avoid an inadvertent ADRV.…”

The 40th Manfred Donike workshop on doping analysis

“…Finally, and particularly relevant for result management and in avoiding unintentional anti‐doping rule violations, urinary excretion profiles for rectal corticoid administrations were investigated. Being prohibited in‐competition only, elimination curves of rectally applied prednisone and prednisolone were determined, especially in consideration of the recently revised reporting levels for corticoids in doping controls 21 . Further, anti‐doping organizations and athletes were made aware of the fact that the consumption of hemp products can result in findings of natural cannabinoids in urine, the presence of which would, per definition, result in an AAF when urine is collected in‐competition.…”