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

Emma Janet Castillo, Silvia Delgado-Aros, Michael Camilleri, Duane Burton, Debra Stephens, Robin O'Connor-Semmes, Ann Walker, Anne Shachoy-Clark, Alan R. Zinsmeister

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

CCK influences satiation and gastric and gall-bladder 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 99mTc-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 GI1S1771X 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume287
Issue number2 50-2
DOIs
StatePublished - Aug 2004

Fingerprint

Gastric Emptying
Fasting
Stomach
Healthy Volunteers
Tablets
Placebos
Area Under Curve
Gallbladder Emptying
Cholecystokinin A Receptor
Satiation
Safety
Photons
Radionuclide Imaging
Nausea
GI 181771X
Pharmacokinetics
Pain

Keywords

  • Accommodation
  • Fasting
  • Satiation
  • Single photon emission computed tomography

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric functions in healthy volunteers. / Castillo, Emma Janet; Delgado-Aros, Silvia; Camilleri, Michael; Burton, Duane; Stephens, Debra; O'Connor-Semmes, Robin; Walker, Ann; Shachoy-Clark, Anne; Zinsmeister, Alan R.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 287, No. 2 50-2, 08.2004.

Research output: Contribution to journalArticle

Castillo, EJ, Delgado-Aros, S, Camilleri, M, Burton, D, Stephens, D, O'Connor-Semmes, R, Walker, A, Shachoy-Clark, A & Zinsmeister, AR 2004, 'Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric functions in healthy volunteers', American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 287, no. 2 50-2. https://doi.org/10.1152/ajpgi.00074.2004
Castillo, Emma Janet ; Delgado-Aros, Silvia ; Camilleri, Michael ; Burton, Duane ; Stephens, Debra ; O'Connor-Semmes, Robin ; Walker, Ann ; Shachoy-Clark, Anne ; Zinsmeister, Alan R. / Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric functions in healthy volunteers. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2004 ; Vol. 287, No. 2 50-2.
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