OMEPRAZOLE FAILS TO ALTER THE CYTOCHROME-P450-DEPENDENT 2-HYDROXYLATION OF ESTRADIOL IN MALE-VOLUNTEERS

Omeprazole, a proton pump inhibitor, is used in the treatment of gastr ointestinal diseases associated with hyperacidity. It binds to, and in hibits, some of the activities of hepatic cytochrome P450 resulting in increased half-lives of certain pharmacologic and endogenous compound s. 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 sensiti ve to a variety of dietary and pharmacologic agents. We therefore stud ied the extent of estradiol 2-hydroxylation in 7 normal male volunteer s 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 afte r omeprazole treatment (27.3 +/- 3.0 vs. 27.5 +/- 3.4%, respectively). The excretion of the endogenous urinary estrogen metabolites, 2-hydro xyestrone, estriol, and estrone was also unaltered by omeprazole. Thes e results show that omeprazole, in contradistinction to other medicati ons used in the treatment of peptic ulcer disease, is without effect o n estradiol metabolism in men.