In Vivo and In Vitro Models for Metabolism and Detection of Anabolic steroids and their Precursors in Humans

Code: 01C10DM

The use of performance-enhancing substances has historic foundations in man’s desire to create a body-building “wonder drug”. In the United States, there has been a rapid rise in the availability and use of unregulated herbal products. The extent of use of these products within the sports community is largely unknown. However, it has been demonstrated that many of these products contain steroids, steroid precursors, or steroid-like compounds (1).

The goal of this proposal is to develop a comprehensive laboratory and clinical model by which new anabolic steroid compounds of interest, particularly those contained in herbal products, can be quickly evaluated to elucidate their metabolism and improve detection. We propose that a dual system of in vitro human liver metabolism studies, coupled with clinical dose-response studies in human subjects, can offer distinct advantages in determining both the profile of metabolites expected after use of a specific compound (or product) as well as the optimum biological specimen(s) for detecting use. Emphasis in this proposal is placed on developing the model with a focus on studying the metabolism and distribution of androstenedione. If successful, this model could be used to study future compounds of interest to the World Anti-Doping Agency and other sports testing bodies, such as 19-norsteroids.

Two general objectives will guide us in reaching our goals. First, we will investigate whether an in vitro human liver assay system can be used to predict the qualitative and quantitative profile of androstenedione and metabolites as compared to in vivo studies. Second, we will evaluate the pharmacokinetics and in vivo metabolism of this steroid precursor in healthy human volunteers. The disposition of parent compound and relevant metabolites into various biological matrices, including plasma, urine, sweat, oral fluids and hair will be investigated. To accomplish our specific aims, we will also develop and rigorously validate sensitive and specific laboratory methods for the analysis of androstenedione and its relevant metabolites in several biological matrices.

Main Findings

(The project was not finished)