Effect of conjugated equine estrogens on oxidative metabolism in middle-aged and elderly postmenopausal women.

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O'Connell MB, Frye RF, Matzke GR, St Peter JV, Willhite LA, Welch MR, Kowal P, LaValleur J

Effect of conjugated equine estrogens on oxidative metabolism in middle-aged and elderly postmenopausal women.

J Clin Pharmacol. 2006 Nov;46(11):1299-307. doi: 10.1177/0091270006292249.

PubMed ID

17050794 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Conjugated estrogens	Cytochrome P450 1A2	Protein	Humans	Unknown	Substrate Inhibitor	Details