Gallbladder volume as a biomarker for the motilin effect in healthy volunteers and patients with functional dyspepsia

Abstract

Decreases in gallbladder volume have been suggested as a biomarker for motilin activity in man. Yet, this could not be confirmed in 4 placebo-controlled cross-over studies with 10–12 subjects each. Therefore a meta-analysis was done on the data from these studies to investigate a motilin effect on gallbladder volume in healthy volunteers and patients with functional dyspepsia (FD). Forty-three healthy volunteers and 10 patients with FD received motilin (4 pmol/kg/min) or placebo in four separate double-blind, randomised, placebo-controlled, cross-over studies. Gallbladder volume was measured by ultrasonography. Analysis of variance of the combined data of these studies was performed to allow differentiation between patients and healthy volunteers. Baseline gallbladder volume was similar for placebo and motilin treatment, and between patients and healthy volunteers. Motilin significantly decreased gallbladder volume in healthy volunteers (p=0.003) and patients (p<0.0001) with the decrease being greater in patients (p=0.03). A linear concentration-response relationship was observed. The motilin effect was consistent across the 4 studies. Interdigestive gallbladder volume is a non-invasive endpoint for motilin activity, displaying a consistent response to motilin and a clear concentration-response relationship. However, it is less suitable as biomarker for future pharmacological studies on motilin agonist or antagonists as the effect is probably indirect and as a large study population is required. Clinical Pharmacology & Therapeutics (2004) 75, P57–P57; doi: 10.1016/j.clpt.2003.11.218