Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women.
This study was conducted to investigate the effect of therapeutic estrogen on cytochrome P450 1A2-mediated metabolism in postmenopausal women using caffeine as a model substrate. Twelve healthy postmenopausal women underwent estrogen replacement therapy in the form of estradiol (Estrace). Estradiol was initiated at a dose of 0.5 mg a day and titrated to achieve a steady-state plasma concentration of 50 to 150 pg/ml. Caffeine metabolic ratios (CMR; paraxanthine/caffeine) were assessed both before and after 8 weeks of estrogen replacement. For the 12 subjects, there was a mean reduction in CMR of -29.2 +/- 25.0 (p = 0.0019). Consistent with previous results found in younger women, these results indicate that exogenous estrogen in older women may inhibit CYP1A2-mediated caffeine metabolism.
Pollock
B G
BG
Geriatric Psychopharmacology Program, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA.
Wylie
M
M
Stack
J A
JA
Sorisio
D A
DA
Thompson
D S
DS
Kirshner
M A
MA
Folan
M M
MM
Condifer
K A
KA
D000368:Aged; D002110:Caffeine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D019388:Cytochrome P-450 CYP1A2 / Q000502:physiology*; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004347:Drug Interactions; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008593:Menopause / Q000378:metabolism*; D008875:Middle Aged; D013806:Theophylline / Q000097:blood*
D000697:Central Nervous System Stimulants; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D002110:Caffeine; D004958:Estradiol; D013806:Theophylline; D019388:Cytochrome P-450 CYP1A2; C021183:1,7-dimethylxanthine