Nobuo Aikawa, Kaori Horikoshi, Hiroshi Maeda, Hiroyuki Kobayashi and
Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.,
1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411 - 8731, Japan
Abstract: The antidiarrheal action of zaldaride maleate (ZAL) after oral, intravenous and subcutaneous administration was examined to determine whether ZAL acts systemically or locally in the intestine of rats. Oral administration of ZAL inhibited castor oil- and 16,16-dimethyl prostaglandin E2-induced diarrhea; however, intravenous or subcutaneous administration of ZAL was ineffective. When ZAL was orally administered, the area under the plasma concentration time curve of the compound was lower than that of ZAL following intravenous or subcutaneous administration at the maximum doses studied. The antidiarrheal effect of ZAL was not dependent on its plasma concentration level. These results suggest that ZAL acts locally in the intestinal tract in rats.
Keywords: Zaldaride maleate, Calmodulin, Diarrhea