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

Mary Beth O'Connell; Reginald F. Frye; Gary R. Matzke; John V. St. Peter; Laurie A. Willhite; Margaret R. Welch; Paul Kowal; June LaValleur

doi:10.1177/0091270006292249

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

Mary Beth O'Connell^*, Reginald F. Frye, Gary R. Matzke, John V. St. Peter, Laurie A. Willhite, Margaret R. Welch, Paul Kowal, June LaValleur

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1299-1307
Number of pages	9
Journal	Journal of Clinical Pharmacology
Volume	46
Issue number	11
DOIs	https://doi.org/10.1177/0091270006292249
Publication status	Published - Nov 2006
Externally published	Yes

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@article{35509a8f3d124eb0a6ad595a4c23c0f0,

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.",

keywords = "Aged, Caffeine, Chlorzoxazone, Cytochrome P450 enzyme system, Dapsone, Dextromethorphan, Drug interactions, Estrogen, Mephenytoin, Metabolism, Postmenopause",

author = "O'Connell, {Mary Beth} and Frye, {Reginald F.} and Matzke, {Gary R.} and {St. Peter}, {John V.} and Willhite, {Laurie A.} and Welch, {Margaret R.} and Paul Kowal and June LaValleur",

year = "2006",

month = nov,

doi = "10.1177/0091270006292249",

language = "English",

volume = "46",

pages = "1299--1307",

journal = "Journal of Clinical Pharmacology",

issn = "0091-2700",

publisher = "Wiley-Blackwell",

number = "11",

}

TY - JOUR

T1 - Effect of conjugated equine estrogens on oxidative metabolism in middle-aged and elderly postmenopausal women

AU - O'Connell, Mary Beth

AU - Frye, Reginald F.

AU - Matzke, Gary R.

AU - St. Peter, John V.

AU - Willhite, Laurie A.

AU - Welch, Margaret R.

AU - Kowal, Paul

AU - LaValleur, June

PY - 2006/11

Y1 - 2006/11

N2 - 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.

AB - 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.

KW - Aged

KW - Caffeine

KW - Chlorzoxazone

KW - Cytochrome P450 enzyme system

KW - Dapsone

KW - Dextromethorphan

KW - Drug interactions

KW - Estrogen

KW - Mephenytoin

KW - Metabolism

KW - Postmenopause

UR - http://www.scopus.com/inward/record.url?scp=33749849449&partnerID=8YFLogxK

U2 - 10.1177/0091270006292249

DO - 10.1177/0091270006292249

M3 - Article

SN - 0091-2700

VL - 46

SP - 1299

EP - 1307

JO - Journal of Clinical Pharmacology

JF - Journal of Clinical Pharmacology

IS - 11

ER -

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

Abstract

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