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Effect of a Triphasic Oral Contraceptive on Drug‐Metabolizing Enzyme Activity as Measured by the Validated Cooperstown 5+1 Cocktail
Author(s) -
Shelepova Tatiana,
Nafziger Anne N.,
Victory Jennifer,
Kashuba Angela D. M.,
Rowland Elizabeth,
Zhang Yanhua,
Sellers Edward,
Kearns Gregory,
Leeder J. Steven,
Gaedigk Andrea,
Bertino Joseph S.
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270005280851
Subject(s) - pharmacology , cyp2c19 , dextromethorphan , medicine , cyp3a , cyp1a2 , drug , cyp2c9 , bioequivalence , pharmacokinetics , crossover study , drug metabolism , dextrorphan , mephenytoin , paraxanthine , active metabolite , oral administration , cytochrome p450 , metabolism , placebo , pathology , alternative medicine
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 Kwith and without a triphasic oral contraceptive (ethinyl estradiol 35 μ g) 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 .