Oral administration of loxiglumide (CCK antagonist) inhibits postprandial gallbladder contraction without affecting gastric emptying

Abstract

The effect of a single oral dose of loxiglumide, a cholecystokinin antagonist, on postprandial gallbladder contraction and on gastric emptying was evaluated in humans. Following a 12-hr fasting period, two tablets of loxiglumide (400 mg each) or placebo was administered on different days, in random order and in a double-blind fashion to 10 healthy volunteers 15 min before the ingestion of a 1050-kcal standard meal. Gallbladder and antral volumes were measured by real-time ultrasonography in basal conditions and at fixed time intervals after the meal. Oral loxiglumide administration was followed by a total inhibition of the gallbladder contraction for 60 min after the end of the meal ingestion. Thereafter, up to the end of the study period, gallbladder volume was larger than that of the placebo study (at 300 min after the meal 2.7 +/- 1.6 ml after placebo and 8.2 +/- 3.5 ml after loxiglumide; P less than 0.008). No difference between placebo and loxiglumide was found in the antral volumes at any time interval (postprandial 63.5 +/- 16.5 ml after placebo and 59.4 +/- 24 ml after loxiglumide; at 300 min after the meal 20.8 +/- 13.3 ml after placebo and 18.9 +/- 9.5 ml after loxiglumide). In conclusion, a single oral dose of loxiglumide at the dose of 800 mg can inhibit postprandial gallbladder contraction without affecting gastric emptying. It would therefore appear that in man endogenous CCK, released after a solid-liquid, caloric, nutrient-balanced meal, plays a major role in the contraction of the gallbladder but does not affect gastric emptying.

Feed intolerance in critical illness is associated with increased basal and nutrient-stimulated plasma cholecystokinin concentrations*

“…However, the effect of CCK antagonists on gastric emptying remains controversial. Although several studies have shown gastric emptying to be accelerated by CCK antagonists (14 -16), two other studies failed to demonstrate an increase in gastric emptying rates (17,18). Nevertheless, current data would suggest a close interaction between nutritional status, CCK, and gastric emptying.…”

Cholecystokinin receptor antagonist loxiglumide modulates plasma levels of gastro‐entero‐pancreatic hormones in man Feedback control of cholecystokinin and gastrin secretion

“…Feedback regulation of CCK release by intraluminal protease activity is probably of minor importance. It has to be noticed that loxiglumide does not elevate basal plasma IR-CCK levels, despite its pronounced effect on fasting gallbladder volume [ 18,19,26]. Only meal-stimulated CCK secretion is further augmented by the receptor antagonist.…”

“…However, this interpretation remains speculative, since gastric emptying was not measured in the present study. The role of CCK in gastric transit in man remains ill-defined, because controversial results have been reported employing different CCK receptor antagonists and different methods for the estimation of gastric emptying rate [16,17,19]. A direct stimulation of insulin release by CCK has been well documented in rats and dogs, but only at supra-physiological doses [5-71.…”

Transient lower oesophageal sphincter relaxations—a pharmacological target for gastro‐oesophageal reflux disease?

“…However, no immunohistochemical studies are yet available to provide anatomical evidence for this pathway. In contrast, a recent study even suggests the existence of a peripheral inhibitory pathway, as both phrenectomy and vagotomy did not prevent crural diaphragm inhibition during oesophageal distension 49–51 …”