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Effects of SK-896, a new human motilin analogue ([Leu13]motilin-Hse), on postoperative ileus in dogs after laparotomy.

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.