St. John’s Wort Modulates the Toxicities and Pharmacokinetics of CPT-11 (Irinotecan) in Rats
CPT-11, pharmacokinetics, St. John’s wort, toxicity
Digital Object Identifier (DOI)
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
Scholar Commons Citation
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, "St. John’s Wort Modulates the Toxicities and Pharmacokinetics of CPT-11 (Irinotecan) in Rats" (2005). Pharmacy Faculty Publications. 17.