Yoshio Kase (1), Terumasa Hayakawa (1), Masaki Aburada (1), Yasuhiro
Komatsu (1) and Tetsuya Kamataki (2)
(1) Central Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-11, Japan
(2) Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060, Japan
Abstract: The possible preventive effect of Kampo medicine Hange-shashin-to (TJ-14) on chronic diarrheal symptoms induced by the administration of the anticancer agent irinotecan hydrochloride (CPT-11) was investigated in the rat. Repeated oral administrations of TJ-14 at 125 and 500 mg/kg significantly prevented the reduction in body weight and the onset of chronic diarrheal symptoms due to CPT-11 in a dose-dependent manner, even though it failed to show a definite effect on acute diarrheal symptoms. In addition, treatment with TJ-14 accelerated the healing of the intestinal tract injured by repeated dosing of CPT-11 and inhibited significantly the increase of colonic prostaglandin E2 (PGE2) which is closely related to the onset of diarrhea. TJ-14 also improved colonic water absorption impaired by repeated dosing of CPT-11 in rats. These results demonstrate that TJ-14 is an effective medicine for the prevention and/or treatment of CPT-11-induced chronic diarrheal symptoms.
Keywords: CPT-11 (irinotecan hydrochloride), Side effect, Chronic diarrheal symptom, Hange-shashin-to, Large intestine