The effect of hormone replacement therapy on CYP3A activity.
Clin Pharmacol Ther
; 68(4): 412-7, 2000 Oct.
Article
em En
| MEDLINE
| ID: mdl-11061581
ABSTRACT
BACKGROUND:
The effect of menopause and hormone replacement therapy on hepatic and intestinal wall CYP3A activity is poorly defined. This study was therefore designed to determine the effect of menopause and estrogen replacement therapy on hepatic and intestinal CYP3A activity with a specific CYP3A substrate, midazolam.METHODS:
Twelve young women (27 +/- 5 years), 10 elderly women receiving estrogen replacement therapy (71 +/- 6 years), and 14 elderly women not receiving estrogen replacement therapy (71 +/- 5 years) received simultaneous intravenous (0.05 mg/kg over 30 minutes) and oral (3 to 4 mg of a stable isotope, 15N3-midazolam) doses of midazolam. Serum and urine samples were assayed for midazolam, 15N3-midazolam, and metabolites by use of gas chromatography-mass spectrometry.RESULTS:
No significant (P > .05) differences were observed in systemic clearance and oral clearance between the three groups. Likewise, no differences were observed in oral, hepatic, or intestinal availability. A significant correlation was observed between oral and intestinal availability and not hepatic availability.CONCLUSION:
Neither menopause nor menopause with estrogen replacement therapy altered intestinal or hepatic CYP3A activity relative to that in a control group of young women.
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Base de dados:
MEDLINE
Assunto principal:
Oxirredutases N-Desmetilantes
/
Progesterona
/
Midazolam
/
Hidrocarboneto de Aril Hidroxilases
/
Terapia de Reposição de Estrogênios
/
Sistema Enzimático do Citocromo P-450
/
Estrogênios
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article