Omeprazole Fails to Alter the Cytochrome P450-Dependent 2-Hydroxylation of Estradiol in Male Volunteers

Abstract

Omeprazole, a proton pump inhibitor, is used in the treatment of gastrointestinal diseases associated with hyperacidity. It binds to, and inhibits, some of the activities of hepatic cytochrome P450 resulting in increased half-lives of certain pharmacologic and endogenous compounds. It may also increase the activity of cytochrome P450 under certain conditions. Oxidative metabolism of endogenous estrogens, particularly the 2-hydroxylation pathway, is P450-dependent, and is highly sensitive to a variety of dietary and pharmacologic agents. We therefore studied the extent of estradiol 2-hydroxylation in 7 normal male volunteers before and during oral treatment with omeprazole 20 mg twice daily. Using a specific in vivo radiometric assay, the mean extent (±SEM) of estradiol 2-hydroxylation was found to be unchanged before and after omeprazole treatment (27.3 ± 3.0 vs. 27.5 ± 3.4%, respectively). The excretion of the endogenous urinary estrogen metabolites, 2-hydroxyestrone, estriol, and estrone was also unaltered by omeprazole. These results show that omeprazole, in contradistinction to other medications used in the treatment of peptic ulcer disease, is without effect on estradiol metabolism in men.

Risk of gynaecomastia associated with cimetidine, omeprazole, and other antiulcer drugs

“…In contrast, ranitidine did not affect 2-hydroxylation nor did omeprazole 19. Our results are in agreement with these biochemical findings.…”

Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein

“…These in vitro data might explain the significant increase in plasma levels of omeprazole and lansoprazole during coadministration of clarithromycin. Although CYP3A4 has been shown to be involved in the metabolism of proton pump inhibitors, no clinically relevant drug interactions could be found with numerous other CYP3A4 substrates (Ching et al 1991;Soons et al 1992;Blohme et al 1993;Galbraith and Michnovicz 1993;Noble et al 1994;Tateishi et al 1995) Therefore, a CYP3A4-independent mechanism was proposed for the clarithromycin/proton pump inhibitor interaction (Gustavson et al 1995;Langtry and Wilde 1997). As clarithromycin has been shown to be effective in inhibiting P-glycoprotein function (Wakasugi et al 1998;Wang et al 2000), inhibition of this transporter might contribute to this interaction.…”

Different mechanisms of handling ingested polycyclic aromatic hydrocarbons in mammalian species: organ-specific response patterns of CYP1A1-induction after oral intake of PAH-contaminated soils

“…Because of limited available data concerning CYP1A1 induction in humans after oral intake of xenobiotics, the toxicologically important question which animal model more closely reflects the human response pattern remains unanswered. Without drawing any conclusion it is noted that oral administration of the proton pump inhibitor and CYP1A1-inducer omeprazole to male human volunteers did not alter their capacity for oestradiol 2-hydroxylation (Galbraith and Michnovicz 1993), although omeprazole is able to induce CYP1A1 in the human duodenum (McDonnell et al 1992). However, increased hepatic oestradiol 2-hydroxylase activity has been reported in rats after oral intake of indole-3-carbinol (Jellinck et al 1991).…”