期刊
PHARMACOTHERAPY
卷 24, 期 11, 页码 1508-1514出版社
WILEY
DOI: 10.1592/phco.24.16.1508.50958
关键词
pharmacokinetics; protein binding; imatinib mesylate; St. John's wort; cytochrome P450 3A4; CYP3A4; metabolic induction effect
资金
- NIGMS NIH HHS [GM24211] Funding Source: Medline
Study Objective. To determine the effect of St. John's wort on the pharmacokinetics of imatinib mesylate. Design. Open-label, complete crossover, fixed-sequence, pharmacokinetic study. Setting. Clinical research center. Subjects. Ten healthy adult volunteers. Intervention. Single 400-mg oral doses of imatinib were administered before and after 2 weeks of treatment with St. John's wort 300 mg 3 times/day. Measurements and Main Results. The pharmacokinetics of imatinib were significantly altered by St. John's wort, with reductions of 32% in the median area under the concentration-time curve from time zero to infinity (p=0.0001), 29% in maximum observed concentration (p=0.005), and 21% in half-life (p=0.0001). Protein binding ranged from 97.7-90.3% (mean 94.9%), was concentration independent, and was not altered by St. John's wort. Therapeutic outcomes of imatinib have been shown to correlate with both dose and drug concentrations. Conclusion. Coadministration of imatinib with St. John's wort may compromise imatinib's clinical efficacy.
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