St. John’s Wort Modulates the Toxicities and Pharmacokinetics of CPT-11 (Irinotecan) in Rats

Document Type

Article

Publication Date

6-2005

Keywords

CPT-11, pharmacokinetics, St. John’s wort, toxicity

Digital Object Identifier (DOI)

https://doi.org/10.1007/s11095-005-4585-0

Abstract

CPT-11 is a DNA topoisomerase I inhibitor for the therapy of colorectal cancer, whereas St. John’s Wort (Hypericum perforatum, SJW) is a widely used herbal anti-depressant. This study aimed to investigate the effects of co-administered SJW on the toxicities and pharmacokinetics of CPT-11 and the underlying mechanisms. The body weight loss, gastrointestinal and hematological toxicities induced by CPT-11, and the pharmacokinetic parameters of CPT-11 were evaluated in rats pretreated with SJW or vehicle. Rats treated with CPT-11 alone experienced rapid decrease in body weight, whereas co-administration of SJW with CPT-11 resulted in lesser body weight loss. The gastrointestinal and hematological toxicities following CPT-11 injection were both alleviated in the presence of SJW. The rat pharmacokinetics of both CPT-11 and its metabolite SN-38 were significantly altered in presence of SJW. In conclusion, co-administered SJW significantly ameliorated the toxicities induced by CPT-11. The protective effect of SJW may be partially due to pharmacokinetic interaction between CPT-11 and SJW.

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Citation / Publisher Attribution

Pharmaceutical Research, v. 22, issue 6, p. 902-914

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