Jpn. J. Pharmacol. 75 (4), 407-413 (1997)

Preventive Effects of Hange-shashin-to on Irinotecan Hydrochloride-Caused Diarrhea and Its Relevance to the Colonic Prostaglandin E2 and Water Absorption in the Rat

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

Copyrightę The Japanese Pharmacological Society 1997

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