Nobuo Aikawa, Kaori Horikoshi, Hiroshi Maeda, Hiroyuki Kobayashi and
Kenji Ohmori
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