Characterization of In Vitro Synthesized Equine Metabolites of the Selective Androgen Receptor Modulators S24 and S4

The fungusCunninghamella eleganscan produce human and equine metabolites of selective androgen receptor modulators (SARMs)

“…However, the amount of unchanged parent compound was larger for S24 than for the other two SARMs (54% of the total signal as compared to 16 and 8% for S1 and S4, respectively). The metabolites found were of the same type as those presented for S1 and they matched those previously described in studies with human and equine liver microsomes (Kuuranne et al 2008;Krug et al 2012). The most abundant type of fungal phase I metabolite (M1) was formed by monohydroxylation (Figure 3c).…”

“…The major fungal biotransformation product of S4 was formed through deacetylation, accounting for more than 90% of the metabolites identified ( Figure 3b). Desacetyl-S4 was among the six most abundant metabolites in the human microsomal study (Kuuranne et al 2008) and the second most intense metabolite in the equine in vitro experiments (Krug et al 2012).…”

“…Hydroxylation including further conjugation was the most common metabolic pathway for S1 and the third most common for S24 in human microsomal preparations (Kuuranne et al 2008). Furthermore, in a recently published paper (Krug et al 2012) it was described that hydroxy-S24 together with its conjugates were the second most common metabolites produced in horse liver microsomes. The good agreement in terms of relative abundance between the isomers of hydroxy-S24 between the fungal and human experiments (Figure 8b) further adds to the view of C. elegans being a relevant metabolic model for this substance class.…”

“…There are a few published studies where the metabolism of different arylpropionamide SARMs have been investigated in vivo in humans (Thevis et al 2010b(Thevis et al , 2011Grata et al 2011), canines (Thevis et al 2010a) and rats and by using in vitro methods based on e.g. human and equine liver microsomes and S9 fractions (Gao et al 2006;Kuuranne et al 2008;Thevis et al 2010a;Krug et al 2012). Knowledge of the metabolic patterns of drugs of abuse is important in order to define appropriate targets for doping control.…”

Investigation of the selective androgen receptor modulators S1, S4 and S22 and their metabolites in equine plasma using high‐resolution mass spectrometry

“…[7] Furthermore, the identification of metabolites also corroborates that a substance has passed through a metabolic system and that an adverse finding is not caused by contamination of the sample. The metabolism of different SARMs of the arylpropionamide class has been studied in vitro in a variety of systems such as human liver microsomes, [8] equine liver microsomes, [9] bovine liver microsomes [10] and fungal incubates, [11] as well as in vivo in both human [12,13] and equine [14] urine. The three aforementioned in vivo studies showed that the SARMs were metabolized rapidly and extensively.…”