| Theme |
Kampo Medicine : New Trends in GI Therapoitics |
| Title |
Prevention of Late Diarrhea as a Side Effect of Irinotecan Hydrochloride by Hange-shashin-to |
| Author |
Tetsuya Kamataki |
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University |
| Author |
Tsuyoshi Yokoi |
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University |
| [ Summary ] |
A method of preventing late diarrhea induced by irinotecan hydrochloride was studied. Hange-shashin-to, a traditional Kampo medicine, was found to potently prevent this form of diarrhea. The concept is based on the following metabolic pathway of irinotecan hydrochloride. 1) The drug is metabolized by esterase to give SN-38, an active metabolite, which is subsequently conjugated by glucuronosyltransferase to give SN-38-glucuronide. 2) The glucuronide is excreted in urine to reach the intestine where the glucuronide is cleaved by beta-glucuronidase present in gut flora to yield SN-38 and glucuronic acid. 3) The SN-38 thus formed was assumed to be the cause of cytotoxic diarrhea.
We found that baicalin, one of the natural glucuronide components of Kampo medicine, was a potent competitive inhibitor of beta-glucuronidase. Hange-shashin-to and Sho-saiko-to, which contain baicalin, as well as baicalin alone, potently inhibited the late diarrhea induced by irinotecan hydrochloride in rats. Clinical trials involving cancer patients further supported the results with experimental animals indicating that Hange-shashin-to effectively prevents the late diarrhea induced by irinotecan hydrochloride. |