Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric functions in healthy volunteers.
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.
Castillo
Emma Janet
EJ
Mayo Clinic, Charlton 8-110, 200 First St. SW, Rochester, MN 55905, USA.
Delgado-Aros
Silvia
S
Camilleri
Michael
M
Burton
Duane
D
Stephens
Debra
D
O'Connor-Semmes
Robin
R
Walker
Ann
A
Shachoy-Clark
Anne
A
Zinsmeister
Alan R
AR
D000328:Adult; D001569:Benzodiazepines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D018925:Chemokines / Q000819:agonists*; D019742:Chemokines, CC; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005215:Fasting / Q000502:physiology*; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D006801:Humans; D008297:Male; D019518:Postprandial Period; D012016:Reference Values; D012996:Solutions; D013270:Stomach / Q000187:drug effects* / Q000502:physiology*; D013607:Tablets
C414047:CCL28 protein, human; D018925:Chemokines; D019742:Chemokines, CC; C488719:GI 181771X; D012996:Solutions; D013607:Tablets; D001569:Benzodiazepines