Drug-drug interactions and masking effects in sport doping: influence of miconazole administration on the urinary concentrations of endogenous anabolic steroids

Abstract

We have investigated the influence of oral miconazole administration on the urinary concentrations of endogenous anabolic androgenic steroids of doping relevance, specifically considering all these compounds routinely monitored in doping control analysis, in the framework of the steroidal module of the “athlete biological passport”, and other steroids, including dehydroepiandrosterone, 5α-dihydrotestosterone, and the hydroxylated metabolites recently proposed as additional markers of the intake of testosterone-related steroids (16α-hydroxy-androsterone, 16α-hydroxy-etiocholanolone, 6β-hydroxy-androsterone, 6β-hydroxy-etiocholanolone, 7α-hydroxy-dehydroepiandrosterone, and 7β-hydroxy-dehydroepiandrosterone). Urinary concentrations of the final metabolic products of the glucocorticoid biosynthetic pathways (11β-hydroxy-androsterone and 11β-hydroxy-etiocholanolone, the formerly used as an endogenous reference compound for the gas chromatography–combustion-isotope ratio mass spectrometry confirmation analysis) were also monitored. Two healthy Caucasian volunteers exhibiting physiologically high testosterone/epitestosterone ratios and elevated concentrations of the main target steroids were selected for the study. Miconazole was administered orally (500 mg/day) for 1 week. Multiple urine samples were collected for 1 week before and during the treatment, and analyzed according to a validated analytical procedure based on gas chromatography–electron ionization-mass spectrometry in selected ion monitoring mode. Our results indicated that oral administration of miconazole decreased the urinary concentrations of androsterone, and to a lesser extent, of etiocholanolone (both detected as the sum of free and glucuronated steroids), and consequently the androsterone/testosterone and androsterone/etiocholanolone ratios. Furthermore, the urinary concentrations of 16α-hydroxy-etiocholanolone, 16α-hydroxy-androsterone, 7β-hydroxy-dehydroepiandrosterone, 6β-hydroxy-etiocholanolone, 7α-hydroxy-dehydroepiandrosterone, 6β-hydroxy-androsterone, 11β-hydroxy-androsterone, and 11β-hydroxy-etiocholanolone were significantly suppressed. This evidence suggests the potential intake of miconazole whenever the urinary steroid profile is characterized by abnormally low concentrations of the above-mentioned steroids.