engleski

Biotransformation of testosterone and epitestosterone by human CYP3A4

Biotransformation of testosterone and its epimer epitestosterone in vitro was investigated using human recombinant CYP3A4. Formats of the recombinant enzyme used were microsomes prepared from insect cells expressing the human enzyme and purified recombinant human CYP3A4 (PANVERA, USA). Structures of metabolites as trimethylsilyl-ether derivatives were determined by the GC/MS method. After incubation with the CYP3A4 following metabolites were identified and quantified: Testosterone, M.+ 432, bis-TMS (Scheme 1): -6beta-Hydroxy-metabolite, M.+520 (M1), tris-TMS. -Three monohydroxy metabolites, M.+ 520 (M2, M3, and M4), tris-TMS. -Androsten-4-ene-3,17-dione, M.+ 430 (M5), bis-TMS. -Monohydroxylated androsten-4-ene- 3,17-dione, M.+ 518 (M6), as tris-TMS (Scheme 1). Epitestosterone, M.+ 432, bis-TMS (Scheme 2): (metabolites M7, M8, and M9 not detected with testosterone) -6beta-Hydroxy-metabolite, M.+520 (M1), tris-TMS. -Five monohydroxy metabolites M.+ 520 (M2, M3 ?, M4, M7, M8), tris-TMS. -Oxidated monohydroxy metabolite M.+ 518 (M9), tris-TMS. -Androsten-4-ene-3,17-dione, M.+ 430 (M5), bis-TMS. -Monohydroxylated androsten-4-ene-3,17-dione, M.+ 518 (M6), tris-TMS (Scheme 2).

Cytochrome P450; testosterone; epitestosterone; CYP3A4; GC/MS; biotransformation

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