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Use of Omeprazole as a CYP3A Probe Drug: Effect of Sex and Menstrual Cycle Phase on CYP3A Activity in Healthy Caucasian Adults

From the Department of Pharmacology, University of Toronto, Toronto, Canada (Dr Zhang, Dr Sellers); Clinical Pharmacology Research Center (Dr Kim, Dr Bertino, Dr Nafziger) and the Department of Medicine (Dr Bertino, Dr Nafziger), Bassett Healthcare, Cooperstown, New York; and the Psychopharmacology and Dependence Research Unit, Sunnybrook and Women's Health Centre, Toronto, Canada (Dr Sellers). Dr Zhang is currently at Pfizer, Global Research and Development, Ann Arbor, Michigan.

To determine the effects of sex and menstrual cycle phase on CYP3A activity and to characterize the intraindividual variability of CYP3A, 24 Caucasian adults were given a single dose of omeprazole every 14th day for 3 months (men) or during the mid-follicular and mid-luteal phases over 3 full menstrual cycles (women). The 2-hour plasma metabolic ratio (MR) (omeprazole/omeprazole sulphone) was used as a measure of CYP3A activity. Overall mean MRs for men (2.4 ± 1.2) and women (2.3 ± 0.93) were not significantly different. In women, no difference in mean omeprazole MR was observed between the mid-follicular phase (2.2 ± 0.85) and mid-luteal phase (2.4 ± 1.0). When all data in the mid-luteal phase were stratified into 3 groups based on the progesterone concentrations (>50 nM [A], 20-50 nM [B], and <20 nM [C]), the MR of group A was significantly lower than that of B and C. The MRs of women during the mid-luteal phase were weakly correlated with progesterone concentrations (r = -0.35; P = .03). Individual coefficients of variation (CV%) in MR ranged from 8.7% to 60.2%, with a median 30.0%. No sex or menstrual cycle differences in CYP3A activity as measured by the probe drug omeprazole were seen. Higher CYP3A activity in women may be associated with higher endogenous progesterone concentrations.

Key Words: Omeprazole • CYP3A • endogenous steroid hormones • progesterone • women

Address for reprints: Edward M. Sellers, MD, PhD, 340 College Street, Suite 400, Toronto, ON M5T 3A9, Canada.

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