title: Effect of conjugated equine estrogens on oxidative metabolism in middle-aged and elderly postmenopausal women.
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.
authors.affiliation: Pharmacy Practice Department Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201-2427, USA. mboconnell@wayne.edu
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: O'Connell
authors.forename: Reginald F
authors.initials: RF
authors.lastname: Frye
authors.forename: Gary R
authors.initials: GR
authors.lastname: Matzke
authors.forename: John V
authors.initials: JV
authors.lastname: St Peter
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Willhite
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Welch
authors.forename: Paul
authors.initials: P
authors.lastname: Kowal
authors.forename: June
authors.initials: J
authors.lastname: LaValleur
mesh_terms: D000368:Aged; D000375:Aging; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D003622:Dapsone / Q000378:metabolism; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006900:Hydroxylation; D050216:Metabolic Detoxication, Phase I / Q000502:physiology*; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism; D017698:Postmenopause
chemical_list: D004966:Estrogens, Conjugated (USP); D003622:Dapsone; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C504573:CYP1A2 protein, human; C045793:CYP2C19 protein, human; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human