© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 16, 1247-1249,
August 21, 2002
© 2002 Oxford University Press
BRIEF COMMUNICATION |
Effects of St. John's Wort on Irinotecan Metabolism
Affiliation of authors: R. H. J. Mathijssen, J. Verweij, P. de Bruijn, W. J. Loos, A. Sparreboom, Department of Medical Oncology, Erasmus MC–Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Correspondence to: Alex Sparreboom, Ph.D., Department of Medical Oncology, Erasmus MC–Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands (e-mail: alexsparreboom{at}hotmail.com).
ABSTRACT
St. John's wort (SJW), a widely used herbal product, has been implicated in drug interactions resulting from the induced expression of the cytochrome P450 CYP3A4 isoform. In this study, we determined the effect of SJW on the metabolism of irinotecan, a pro-drug of SN-38 and a known substrate for CYP3A4. Five cancer patients were treated with irinotecan (350 mg/m2, intravenously) in the presence and absence of SJW (900 mg daily, orally for 18 days) in an unblinded, randomized crossover study design. The plasma levels of the active metabolite SN-38 decreased by 42% (95% confidence interval [CI] = 14% to 70%) following SJW cotreatment with 1.0 µM x h (95% CI = 0.34 µM x h to 1.7 µM x h) versus 1.7 µM x h (95% CI = 0.83 µM x h to 2.6 µM x h) (P = .033, two-sided paired Student's t test). Consequently, the degree of myelosuppression was substantially worse in the absence of SJW. These findings indicate that patients on irinotecan treatment should refrain from taking SJW because plasma levels of SN-38 were dramatically reduced, which may have a deleterious impact on treatment outcome.
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