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.
Furuta
Yoshiyuki
Y
Central Research Laboratory, Sanwa Kagaku Kenkyusho Co, Ltd, Inabe-gun, Mie, Japan. y_furuta@mb4.skk-net.com
Takeda
Motohiro
M
Nakayama
Yukiharu
Y
Ito
Mikio
M
Suzuki
Yoshio
Y
D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007275:Injections, Intravenous; D007415:Intestinal Obstruction / Q000188:drug therapy* / Q000503:physiopathology; D007813:Laparotomy / Q000009:adverse effects; D008297:Male; D009037:Motilin / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000188:drug therapy* / Q000503:physiopathology
C414785:SK896; D009037:Motilin