Journal Article

Effects of St. John's Wort on Irinotecan Metabolism

Ron H. J. Mathijssen, Jaap Verweij, Peter de Bruijn, Walter J. Loos and Alex Sparreboom

in JNCI: Journal of the National Cancer Institute

Volume 94, issue 16, pages 1247-1249
Published in print August 2002 | ISSN: 0027-8874
Published online August 2002 | e-ISSN: 1460-2105 | DOI: https://dx.doi.org/10.1093/jnci/94.16.1247
Effects of St. John's Wort on Irinotecan Metabolism

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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 × h (95% CI = 0.34 μM × h to 1.7 μM × h) versus 1.7 μM × h (95% CI = 0.83 μM × h to 2.6 μM × 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.

Journal Article.  2150 words.  Illustrated.

Subjects: Medical Oncology

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