Abstract | OBJECTIVES: METHODS: RESULTS: Concomitant use of St John's wort was associated with a significant (P <.05) increase in the oral clearance of norethindrone (8.2 +/- 2.7 L/h to 9.5 +/- 3.4 L/h, P =.042) and a significant reduction in the half-life of ethinyl estradiol (23.4 +/- 19.5 hours to 12.2 +/- 7.1 hours, P =.023). The oral clearance of midazolam was significantly increased (109.2 +/- 47.9 L/h to 166.7 +/- 81.3 L/h, P =.007) during St John's wort administration, but the systemic clearance of midazolam was unchanged (37.7 +/- 11.3 L/h to 39.0 +/- 10.3 L/h, P =.567). Serum concentrations of follicle-stimulating hormone, luteinizing hormone, and progesterone were not significantly affected by St John's wort dosing (P >.05). Breakthrough bleeding occurred in 2 of 12 women in the control phase compared with 7 of 12 women in the St John's wort phase. The oral clearance of midazolam after St John's wort dosing was greater in women who had breakthrough bleeding (215.9 +/- 66.5 L/h) than in those who did not (97.5 +/- 37.2 L/h) (P =.005). CONCLUSION:
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Authors | Stephen D Hall, Zaiqi Wang, Shiew-Mei Huang, Mitchell A Hamman, Nina Vasavada, Adegboyega Q Adigun, Janna K Hilligoss, Margaret Miller, J Christopher Gorski |
Journal | Clinical pharmacology and therapeutics
(Clin Pharmacol Ther)
Vol. 74
Issue 6
Pg. 525-35
(Dec 2003)
ISSN: 0009-9236 [Print] United States |
PMID | 14663455
(Publication Type: Clinical Trial, Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Contraceptives, Oral, Combined
- Drug Combinations
- Hypnotics and Sedatives
- Plant Preparations
- Norinyl
- Follicle Stimulating Hormone
- Mestranol
- Aryl Hydrocarbon Hydroxylases
- Cytochrome P-450 CYP3A
- Oxidoreductases, N-Demethylating
- Midazolam
- Norethindrone
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Topics |
- Administration, Oral
- Adult
- Area Under Curve
- Aryl Hydrocarbon Hydroxylases
(biosynthesis, metabolism)
- Contraceptives, Oral, Combined
(blood, metabolism, pharmacokinetics)
- Cytochrome P-450 CYP3A
- Drug Combinations
- Drug Interactions
- Enzyme Induction
(drug effects)
- Female
- Follicle Stimulating Hormone
(blood)
- Half-Life
- Humans
- Hypericum
- Hypnotics and Sedatives
(pharmacokinetics)
- Injections, Intravenous
- Menstrual Cycle
(drug effects)
- Mestranol
(metabolism, pharmacokinetics)
- Metabolic Clearance Rate
- Midazolam
(pharmacokinetics)
- Norethindrone
(metabolism, pharmacokinetics)
- Oxidoreductases, N-Demethylating
(biosynthesis, metabolism)
- Plant Preparations
(administration & dosage, pharmacology)
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