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Preliminary Evaluation of Progestins as Inducers of Cytochrome P450 3A4 Activity in Postmenopausal Women
Author(s) -
Tsunoda Shirley M.,
Harris Robert Z.,
Mroczkowski Patrick J.,
Benet Leslie Z.
Publication year - 1998
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127009803801208
Subject(s) - cyp3a4 , progestin , pharmacology , crossover study , pharmacokinetics , erythromycin , medicine , medroxyprogesterone acetate , endocrinology , chemistry , cytochrome p450 , metabolism , antibiotics , hormone , biochemistry , alternative medicine , pathology , placebo
The effects of intramuscularly and orally administered medroxyprogesterone acetate on cytochrome P450 3A4 (CYP3A4) activity were investigated in twelve postmenopausal women in a randomized, crossover study. Unbound prednisolone clearance and the erythromycin breath test were used as markers of CYP3A4 activity. After 2 months of intramuscular progestin therapy, unbound prednisolone clearance increased by 25% in five of six subjects. Similarly, after intramuscular progestin therapy, results from the erythromycin breath test showed a 23% mean increase in CYP3A4 activity. In contrast, 2 months of oral progestin therapy had no effect on prednisolone pharmacokinetics or erythromycin metabolism. These results suggest that parenterally but not orally administered progestins may induce or activate the CYP3A4 enzyme system, leading to an increased metabolism of many CYP3A4 substrates.