The effects of
SK-896, a new human
motilin analogue ([Leu13]
motilin-Hse), on digestive tract motility in postoperative
ileus were evaluated in a dog model of
ileus after
laparotomy.
SK-896 was intravenously administered at 0.17, 0.33 and 0.67 microg/kg starting soon after operation and then at 6-h intervals, for a total of 9 times.
SK-896 progressively, dose-dependently and significantly increased the duodenal motility from 1 h after operation. The recovery time of the gastrointestinal-interdigestive migrating complex (GI-IMC) activity, which is an
indicator of normal gastrointestinal tract activity after
laparotomy, was 56.5 +/- 5.0 h in the control group.
SK-896 significantly shortened this recovery time. On the other hand, the plasma
SK-896 concentrations declined diexponentially after administration, and can be described by a linear pharmacokinetic model within the dose range used. In addition, the pharmacokinetics of
SK-896 did not change significantly at any postoperative time. There was no correlation between the plasma
SK-896 concentrations and the intensity of duodenal motility, because the activity in the duodenum decreased transiently 13 h after
laparotomy and increased with time thereafter. The changes in the activity are considered to reflect the progressive changes in the state of
ileus. In conclusion,
SK-896 increased the duodenal motility significantly, shortening the recovery time of GI-IMC-like activity in dogs with post-
laparotomy ileus. Therefore, it is expected from these results that
SK-896 would be useful and effective for the treatment of gastroparalysis after abdominal surgery.