HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Sign In to gain access to subscriptions and/or personal tools.

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Shelepova, T. Articles by Bertino, J. S. Search for Related Content PubMed PubMed Citation Articles by Shelepova, T. Articles by Bertino, J. S., Jr.

Effect of a Triphasic Oral Contraceptive on Drug-Metabolizing Enzyme Activity as Measured by the Validated Cooperstown 5+1 Cocktail

From the Department of Medicine, Clinical Pharmacology Research Center (Dr Shelepova, Dr Nafziger, Dr Bertino), and The Research Institute (Dr Nafziger, Ms Victory, Dr Bertino), Bassett Healthcare, Cooperstown, New York; University of North Carolina School of Pharmacy, Chapel Hill, North Carolina (Dr Kashuba, Ms Rowland); Psychopharmacology and Dependence Research Unit, Sunny Brook & Women's College, University of Toronto, Toronto, Ontario, Canada (Dr Zhang, Dr Sellers); and Division of Pediatric Clinical Pharmacology and Medical Toxicology, Children's Mercy Hospital and Clinics, Kansas City, Missouri (Dr Kearns, Dr Leeder, Dr Gaedigk).

The effects of a common oral contraceptive preparation on the activity of 7 drug-metabolizing enzymes were investigated using the validated Cooperstown 5+1 Cocktail. In a randomized crossover fashion, 10 premenopausal women received caffeine, dextromethorphan, omeprazole, intravenous midazolam, and warfarin + vitamin K with and without a triphasic oral contraceptive (ethinyl estradiol 35 µg) and varying doses of daily norgestimate (0.18, 0.215, and 0.25 mg). Bioequivalence testing showed nonequivalence in drug versus no-drug treatment on the activity of drug-metabolizing enzymes (as reflected by metabolite ratios following probe drug administration); the activity of CYP1A2, CYP2C19, and NAT-2 decreased following the oral contraceptive, whereas the activity of CYP2C9 and CYP2D6 increased. No effects on xanthine oxidase or hepatic CYP3A were seen. Application of a non-parametric statistical testing approach revealed a significant difference only for CYP1A2 and CYP2C19. This triphasic oral contraceptive may have a clinically significant effect on the activity of some drug-metabolizing enzymes.

Key Words: Oral contraceptives • cocktail • cytochrome P450 • drug-metabolizing enzymes

Address for reprints: Joseph S. Bertino Jr., PharmD, Scientific Director, Ordway Research Institute Drug Development Center, 150 New Scotland Avenue, Albany, NY 12208.

This article has been cited by other articles:

				J. Hilli, T. Korhonen, M. Turpeinen, J. Hokkanen, S. Mattila, and K. Laine The Effect of Oral Contraceptives on the Pharmacokinetics of Melatonin in Healthy Subjects With CYP1A2 g.-163C>A Polymorphism J. Clin. Pharmacol., August 1, 2008; 48(8): 986 - 994. [Abstract] [Full Text] [PDF]

				N. B. Sandson, K. L. Cozza, S. C. Armstrong, G. Eckermann, B. A. Fischer, and B. Phillips Clozapine Case Series Psychosomatics, April 1, 2007; 48(2): 170 - 175. [Abstract] [Full Text] [PDF]

				M. B. O'Connell, R. F. Frye, G. R. Matzke, J. V. St. Peter, L. A. Willhite, M. R. Welch, P. Kowal, and J. LaValleur Effect of Conjugated Equine Estrogens on Oxidative Metabolism in Middle-aged and Elderly Postmenopausal Women. J. Clin. Pharmacol., November 1, 2006; 46(11): 1299 - 1307. [Abstract] [Full Text] [PDF]