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Effect of Conjugated Equine Estrogens on Oxidative Metabolism in Middle‐aged and Elderly Postmenopausal Women
Author(s) -
O'Connell Mary Beth,
Frye Reginald F.,
Matzke Gary R.,
Peter John V. St.,
Willhite Laurie A.,
Welch Margaret R.,
Kowal Paul,
LaValleur June
Publication year - 2006
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 - 10.1177/0091270006292249
Subject(s) - cyp1a2 , dextromethorphan , cyp2d6 , mephenytoin , pharmacology , chlorzoxazone , cyp2c19 , metabolism , endocrinology , dextrorphan , medicine , chemistry , dapsone , cyp2e1 , cytochrome p450 , immunology
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.