St. John's wort modulates the toxicities and pharmacokinetics of CPT-11 (Irinotecan) in rats

Zeping Hu, Xiaoxia Yang, Paul Chi Liu Ho, Eli Chan, Yung Chan Sui, Congjian Xu, Xiaotian Li, Yi Zhun Zhu, Wei Duan, Xiao Chen, Min Huang, Hongyuan Yang, Shufeng Zhou

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Purpose. 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. Methods. 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. Results. 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. Conclusions. 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.

Original languageEnglish (US)
Pages (from-to)902-914
Number of pages13
JournalPharmaceutical Research
Volume22
Issue number6
DOIs
StatePublished - Jun 1 2005

Keywords

  • CPT-11
  • Pharmacokinetics
  • St. John's wort
  • Toxicity

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'St. John's wort modulates the toxicities and pharmacokinetics of CPT-11 (Irinotecan) in rats'. Together they form a unique fingerprint.

  • Cite this

    Hu, Z., Yang, X., Ho, P. C. L., Chan, E., Sui, Y. C., Xu, C., Li, X., Zhu, Y. Z., Duan, W., Chen, X., Huang, M., Yang, H., & Zhou, S. (2005). St. John's wort modulates the toxicities and pharmacokinetics of CPT-11 (Irinotecan) in rats. Pharmaceutical Research, 22(6), 902-914. https://doi.org/10.1007/s11095-005-4585-0