J Clin Pharmacol
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DRUG METABOLISM

Effect of Conjugated Equine Estrogens on Oxidative Metabolism in Middle-aged and Elderly Postmenopausal Women

Mary Beth O'Connell, PharmD, Reginald F. Frye, PharmD, PhD, Gary R. Matzke, PharmD, John V. St. Peter, PharmD, Laurie A. Willhite, PharmD, Margaret R. Welch, PharmD, Paul Kowal, PharmD, MS and June LaValleur, MD

From the Pharmacy Practice Department Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan (Dr O'Connell); College of Pharmacy, University of Florida, Gainesville, Florida (Dr Frye); College of Pharmacy, Virginia Commonwealth University, Richmond, Virginia (Dr Matzke); Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (Dr St. Peter); Fairview University Medical Center, Minneapolis, Minnesota (Dr Willhite); formally at the University of Minnesota, College of Pharmacy (Dr Welch, Dr Kowal), and Obstetrics and Gynecology Department, School of Medicine, University of Minnesota, Minneapolis, Minnesota (Dr LaValleur).

The effects of conjugated equine estrogens (CEE) 0.625 mg daily on cytochrome P450 (CYP) were quantified in 12 middle-aged and 13 elderly postmenopausal women at baseline and 6 months later. CYP phenotype was characterized by caffeine (CYP1A2), chlorzoxazone (CYP2E1), dapsone (CYP, N-acetyltransferase 2), dextromethorphan (CYP2D6), and mephenytoin (CYP2C19) metabolism. CEE significantly decreased CYP1A2 (caffeine metabolic ratio: 0.57 ± 0.20 before, 0.40 ± 0.20 after, P = .001) and significantly increased CYP2D6 (dextromethorphan/dextrorphan ratio: 0.0116 ± 0.0143 before, 0.0084 ± 0.0135 after, P = .022) metabolism. CEE had no overall effect on CYP2C19, CYP2E1, CYP-mediated dapsone metabolism, and N-acetyltransferase 2. The dextromethorphan metabolic ratio decreased only in the seniors. The dapsone recovery ratio decreased in the middle-aged group and increased in the seniors. CEE significantly influenced CYP1A2, CYP2D6, and CYP-mediated dapsone oxidative metabolism but not CYP2C19, CYP2E1, or N-acetyltransferase 2 metabolism in postmenopausal women. Age influenced CYP2D6 metabolism and dapsone hydroxylation.

Key Words: Estrogen • metabolism • cytochrome P450 enzyme system • caffeine • chlorzoxazone • dapsone • dextromethorphan • mephenytoin • drug interactions • aged • postmenopause

Address for reprints: Mary Beth O'Connell, PharmD, Wayne State University, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Avenue, Suite 2190, Detroit, MI 48201-2427; e-mail: mboconnell{at}wayne.edu.


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