The effect of cholecystokinin antagonism on postprandial lower oesophagealsphincter function in asymptomatic volunteers and patients with reflux disease
Nj. Trudgill et al., The effect of cholecystokinin antagonism on postprandial lower oesophagealsphincter function in asymptomatic volunteers and patients with reflux disease, ALIM PHARM, 15(9), 2001, pp. 1357-1364
Background: Postprandial acid reflux is thought to be mediated by the incre
ase in transient lower oesophageal sphincter relaxations (TLOSR) frequency
and fall in lower oesophageal sphincter (LOS) pressure seen after ingestion
of a meal, Studies in animals and healthy volunteers suggest that cholecys
tokinin (CCK) may play a role.
Aim: To study the role of CCK in postprandial LOS function using the CCK an
tagonist loxiglumide. Subjects: 10 asymptomatic volunteers (7 male, 20-29 y
ears) and 9 patients with symptomatic gastrooesophageal reflux (4 male, 33-
66 years).
Methods: Oesophageal, LOS and gastric pressure and oesophageal pH readings
were recorded for 1 h before and 2 h after intragastric, infusion of a 200
kCal, 300 mL long chain triglyceride meal. Each subject underwent two studi
es and received intravenous loxiglumide or placebo infusion in randomized o
rder.
Results: During placebo infusion, postprandial LOS pressure fell [volunteer
s: 17 (9-31) to 7 (1-19) mmHg (P < 0.01), patients: 15 (6-26) to 9 (2-21) m
mHg (P = 0.02)] and TLOSR frequency increased [volunteers: 0 (0-1) to 2 (0-
7) per hour (P 0.01), patients: 0 (0-3) to 2 (0-10) per hour (P 0.03)]. Lox
iglumide infusion attenuated the postprandial fall in LOS pressure and the
postprandial increase in TLOSR frequency [volunteers: 0 (0-3) per hour (P =
0.04 vs. placebo), patients: 0 (0-2) per hour (P = 0.03 vs. placebo)], but
it had only modest effects on postprandial acid exposure [volunteers: plac
ebo 45 (0-1725) vs. loxiglumide 0 (0-443) seconds (N.S.), patients: placebo
60 (0-3442) seconds vs. loxiglumide 31 (0-1472) seconds (N.S.)].
Conclusions: Loxiglumide inhibits TLOSR and attenuates the fall in LOS pres
sure following a meal, but has only modest effects on postprandial gastro-o
esophageal acid reflux.