Abiraterone inhibits 17 α-hydroxylase/C17,20 lyase (CYP17A1), an enzyme which is expressed in testicular, adrenal, and prostatic tumor tissues. CYP17 catalyzes two sequential reactions: (a) the conversion of pregnenolone and progesterone to their 17-α-hydroxy derivatives by its 17 α-hydroxylase activity, and (b) the subsequent formation of dehydroepiandrosterone (DHEA) andandrostenedione, respectively, by its C17,20 lyase activity. DHEA and androstenedione are androgens and precursors of testosterone. Inhibition of CYP17 activity by abiraterone thus decreases circulating levels of testosterone. It is a CYP3A4 substrate and hence should be administered in patients concurrently on CYP3A4 inhibitors or inducers. Likewise it inhibits CYP1A2, CYP2C9 and CYP3A4 and hence should not be given to patients concurrently being treated with substrates of either of these enzymes.
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