Do men and women differ in proximal small intestinal CYP3A or Pglycoprotein expression? Drug Metab Dispos

The higher systemic clearance of some CYP3A4 [whether also P-glycoprotein (P-gp)] drug substrates in women versus men is attributed in part to a higher hepatic CYP3A4 content in women. This, combined with the general paucity of reported sex differ-ences in the apparent oral clearance of CYP3A4 substrates, sug-gested a sex-dependent expression of CYP3A4 in the intestine, but in a pattern opposite to that in the liver. Accordingly, duodenal biopsies obtained from healthy men (n 46) and women (n 45) were analyzed, by Western blot, for relative CYP3A4, as well as for CYP3A5 and P-gp, expression levels. Among all subjects, CYP3A4 and P-gp varied 8- and 10-fold, respectively. CYP3A5, which was readily detected in 27 % of these predominantly white individuals, varied 7-fold. For all three proteins, a sex difference was not detected (p> 0.55). The lack of a difference remained for CYP3A4 and P-gp when the analysis was restricted to white individuals (