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INVESTIGATION INTO THE EFFECTS OF TESTOSTERONE ON DRUG METABOLIZING ENZYMES IN HEPATIC AND INTESTINAL HUMAN CELL LINES

Testosterone is a well‐established probe substrate for assessing functional levels of cytochrome P450 (CYP) 3A4‐mediated metabolism. Parenteral testosterone replacement therapy is commonly prescribed for male hypogonadism, given the low oral bioavailability of oral testosterone. However, some investigators are exploring the oral delivery of testosterone or its esters using specialized formulations that might promote lymphatic intestinal absorption. Exogenous administration of hormones is known to down‐regulate endogenous production, which could lead to less than expected increases in exposure with repeated administration, but other factors such as self‐induction of metabolism could also contribute. There is little if any substantive information available that sheds light on whether or not testosterone has any inductive effects on CYP3A4 mediated metabolism, or on any other CYP isoforms. The intent of this study was to use intestinal and hepatic human cell lines to assess for possible induction of CYP3A4 and CYP1A1.