Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric functions in healthy volunteers

Am J Physiol Gastrointest Liver Physiol. 2004 Aug;287(2):G363-9. doi: 10.1152/ajpgi.00074.2004.

Abstract

CCK influences satiation and gastric and gallbladder emptying. GI181771X is a novel oral CCK-1 agonist; its effects on gastric emptying of solids, accommodation, and postprandial symptoms are unclear. Effects of four dose levels of the oral CCK-1 agonist GI181771X and placebo on gastric functions and postprandial symptoms were compared in 61 healthy men and women in a randomized, gender-stratified, double-blind, double-dummy placebo-controlled, parallel group study. Effects of 0.1, 0.5, and 1.5 mg of oral solution and a 5.0-mg tablet of GI181771X on gastric emptying of solids by scintigraphy, gastric volume by (99m)Tc-single photon emission computed tomographic imaging, maximum tolerated volume of Ensure, and postprandial nausea, bloating, fullness, and pain were studied. On each of 3 study days, participants received their randomly assigned treatment. Adverse effects and safety were monitored. There were overall group effects of GI181771X on gastric emptying (P < 0.01) and fasting and postprandial volumes (P = 0.036 and 0.015, respectively). The 1.5-mg oral solution of GI181771X significantly delayed gastric emptying of solids (P < 0.01) and increased fasting (P = 0.035) gastric volumes without altering postprandial (P = 0.056) gastric volumes or postprandial symptoms relative to placebo. The effect of the 5.0-mg tablet on gastric emptying of solids did not reach significance (P = 0.052). Pharmacokinetic profiles showed the highest area under the curve over 4 h for the 1.5-mg solution and a similar area under the curve for the 0.5-mg solution and 5-mg tablet. Adverse effects were predominantly gastrointestinal and occurred in a minority of participants. GI181771X delays gastric emptying of solids and exhibits an acceptable safety profile in healthy participants. CCK-1 receptors can be modulated to increase fasting gastric volume.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Benzodiazepines / adverse effects
  • Benzodiazepines / pharmacokinetics
  • Benzodiazepines / pharmacology*
  • Chemokines / agonists*
  • Chemokines, CC
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Fasting / physiology*
  • Female
  • Gastric Emptying / drug effects*
  • Humans
  • Male
  • Postprandial Period*
  • Reference Values
  • Solutions
  • Stomach / drug effects*
  • Stomach / physiology*
  • Tablets

Substances

  • CCL28 protein, human
  • Chemokines
  • Chemokines, CC
  • GI 181771X
  • Solutions
  • Tablets
  • Benzodiazepines