Effect of conjugated equine estrogens on oxidative metabolism in middle-aged and elderly postmenopausal women.
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.
O'Connell
Mary Beth
MB
Pharmacy Practice Department Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201-2427, USA. mboconnell@wayne.edu
Frye
Reginald F
RF
Matzke
Gary R
GR
St Peter
John V
JV
Willhite
Laurie A
LA
Welch
Margaret R
MR
Kowal
Paul
P
LaValleur
June
J
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
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