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

Hu, Zeping, Yang, Xiaoxia, Ho, Paul Chi-Liu, Chan, Eli, Chan, Sui Yung, Xu, Congjian, Li, Xiaotian, Zhu, Yi-Zhun, Duan, Wei, Chen, Xiao, Huang, Min, Yang, Hongyuan and Zhou, Shufeng 2005, St Johns wort modulates the toxicities and parmacokinetics of CPT-11 (Irontecan) in rats, Pharmaceutical research, vol. 22, no. 6, pp. 902-914.

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Title St Johns wort modulates the toxicities and parmacokinetics of CPT-11 (Irontecan) in rats
Author(s) Hu, Zeping
Yang, Xiaoxia
Ho, Paul Chi-Liu
Chan, Eli
Chan, Sui Yung
Xu, Congjian
Li, Xiaotian
Zhu, Yi-Zhun
Duan, Wei
Chen, Xiao
Huang, Min
Yang, Hongyuan
Zhou, Shufeng
Journal name Pharmaceutical research
Volume number 22
Issue number 6
Start page 902
End page 914
Publisher Springer Netherlands
Place of publication Amsterdam, The Netherlands
Publication date 2005-06
ISSN 0724-8741
1573-904X
Keyword(s) CPT-11
pharmacokinetics
St. John's wort
toxicity
Summary 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.
Language eng
Field of Research 111502 Clinical Pharmacology and Therapeutics
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2005, Springer Science + Business Media, Inc.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30009197

Document type: Journal Article
Collection: School of Medicine
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