The influence of St. John's Wort on the pharmacokinetics and protein binding of imatinib mesylate

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.