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St Johns wort modulates the toxicities and parmacokinetics of CPT-11 (Irontecan) in rats

journal contribution
posted on 2005-06-01, 00:00 authored by Z Hu, X Yang, P L Ho, E Chan, S Chan, C Xu, X Li, Y Z Zhu, Wei DuanWei Duan, X Chen, M Huang, H Yang, S Zhou
CPT-11 is a DNA topoisomerase I inhibitor for the therapy of colorectal cancer, whereas St. Johnrsquos 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.

History

Journal

Pharmaceutical research

Volume

22

Issue

6

Pagination

902 - 914

Publisher

Springer Netherlands

Location

Amsterdam, The Netherlands

ISSN

0724-8741

eISSN

1573-904X

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2005, Springer Science + Business Media, Inc.