Effects of SK-896, a New Human Motilin Analogue ([Leu13]motilin-Hse), on Postoperative Ileus in Dogs after Laparotomy.

Abstract

The effects of SK-896, a new human motilin analogue ([Leu 13 ]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 m mg/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.

Effect of prolonged general anesthesia with sevoflurane and laparoscopic surgery on gastric and small bowel propulsive motility and pH in dogs

“…However, anesthetizing dogs for 2.5–3 hours with pentobarbital showed similar decreased GI tract motility that lasted 13 hours, which is equivalent to what we found in the gastric group (Furuta et al. ). However, it is unknown if shorter anesthesia periods will have different effects on the GI tract.…”

Motilin: from gastric motility stimulation to hunger signalling

“…In dogs, SK-896 induced interdigestive migrating contractions 221 . Moreover, SK-896 improved gastrointestinal motility in postoperative ileus in dogs 222,223 . The effects on gastrointestinal motility in healthy human volunteers were less pronounced 224 .…”

Quantitative Analytical Method for Determining the Levels of Gastric Inhibitory Polypeptides GIP1–42 and GIP3–42 in Human Plasma Using LC–MS/MS/MS

“…Two grams of charcoal was added to every 10.0 mL of plasma, and this mixture was agitated for 12 h at 4 °C. After centrifuging for 1 h at 4 °C and 105,000 × g , the supernatant was filtered using a 0.22-μm filter …”