Xiao-Chai-Hu-Tang (XCHT) Intervening Irinotecan's Disposition: The Potential of XCHT in Alleviating Irinotecan-Induced Diarrhea.

Abstract

BACKGROUND:

Diarrhea is a severe side effect of irinotecan, a pro-drug of SN-38 used for the treatment of many types of cancers. Pre-clinical and clinical studies showed that decreasing the colonic exposure of SN-38 can mitigate irinotecan-induced diarrhea.

OBJECTIVE:

The purpose of this study is to evaluate the anti-diarrhea potential of Xiao-Chai-Hu-Tang (XCHT), a traditional Chinese herbal formula, against irinotecan-induced diarrhea by determining if and how XCHT alters the disposition of SN-38.

METHODS:

LC-MS/MS was used to quantify the concentrations of irinotecan and its major metabolites (i.e., SN-38, SN-38G). An Intestinal perfusion model was used to determine the effect of XCHT on the biliary and intestinal secretions of irinotecan, SN-38, and SN-38G. Pharmacokinetic (PK) studies were performed to determine the impact of XCHT on the blood and fecal concentrations of irinotecan, SN-38, and SN-38G.

RESULTS:

The results showed that XCHT significantly inhibits both biliary and intestinal excretions of irinotecan, SN-38, and SN-38G (range: 35% to 95%). PK studies revealed that the fecal concentrations of irinotecan and SN-38 were significantly decreased from 818.35 ± 120.2 to 411.74 ± 138.83 µg/g or from 423.95 ± 76.44 to 245.63 ± 56.72 µg/g (p<0.05) by XCHT, respectively, suggesting the colonic exposure of SN-38 is significantly decreased by XCHT. PK studies also showed that the plasma concentrations of irinotecan, SN-38, and SN-38G were not affected by XCHT.

CONCLUSION:

In conclusion, XCHT significantly decreased the exposure of SN-38 in the gut without affecting its plasma level, thereby possessing the potential of alleviating irinotecan-induced diarrhea without negatively impacting its therapeutic efficacy.

• Authors: Rongjin Sun, Sumit Basu, Min Zeng, Robin Sunsong, Li Li, Romi Ghose, Wei Wang, Zhongqiu Liu, Ming Hu, Song Gao
• Journal: Current cancer drug targets (Curr Cancer Drug Targets) Vol. 19 Issue 7 Pg. 551-560 ( 2019) ISSN: 1873-5576 [Electronic] Netherlands
• PMID: 31509102 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• Drugs, Chinese Herbal
• shosaiko-to
• Irinotecan

Topics

• Animals
• Biliary Tract (drug effects, metabolism)
• Diarrhea (chemically induced, drug therapy, metabolism, pathology)
• Drugs, Chinese Herbal (pharmacology)
• Intestinal Mucosa (drug effects, metabolism)
• Irinotecan (pharmacokinetics, toxicity)
• Male
• Rats
• Rats, Wistar
• Tissue Distribution