St. John's Wort modulates the toxicities and pharmacokinetics of CPT-11 (irinotecan) in rats.
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.
Hu
Zeping
Z
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
Yang
Xiaoxia
X
Ho
Paul Chi-Liu
PC
Chan
Eli
E
Chan
Sui Yung
SY
Xu
Congjian
C
Li
Xiaotian
X
Zhu
Yi-Zhun
YZ
Duan
Wei
W
Chen
Xiao
X
Huang
Min
M
Yang
Hongyuan
H
Zhou
Shufeng
S
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics* / Q000633:toxicity*; D019540:Area Under Curve; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control; D004347:Drug Interactions; D006207:Half-Life; D020902:Hypericum; D007410:Intestinal Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000473:pathology; D000077146:Irinotecan; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin