Gallbladder volume as a biomarker for the motilin effect in healthy volunteers and patients with functional dyspepsia.
OBJECTIVE
To investigate a motilin effect on gallbladder volume in healthy volunteers and patients with functional dyspepsia.


METHODS
Forty-three healthy volunteers and 10 patients with functional dyspepsia received motilin (4 pmol.min/kg) or placebo in four separate double-blind, randomized, placebo-controlled, cross-over studies. The gallbladder volume was measured by ultrasonography. Analysis of variance of the combined data of these studies was performed to investigate a motilin effect on gallbladder volume and potential differences between patients and healthy volunteers.


RESULTS
The baseline gallbladder volume was similar for placebo and motilin treatment, as well as for patients and healthy volunteers. Motilin, compared with placebo, significantly decreased the gallbladder volume in healthy volunteers (P = 0.003) and patients (P < 0.0001). A linear concentration-response relationship was observed. The decrease in gallbladder volume by motilin was greater in patients (P = 0.03). The motilin effect was consistent between studies.


CONCLUSIONS
The interdigestive gallbladder volume is a non-invasive end-point for motilin activity, displaying a consistent response across studies, a clear response to motilin and a clear concentration-response relationship. However, it is less suitable as a biomarker for future pharmacological studies on motilin agonists or antagonists as the effect is probably indirect, and a relatively large study population of 27 subjects is required to demonstrate a 15% decrease in gallbladder volume. Further investigation is required to confirm altered gallbladder motility as a feature of functional dyspepsia.
Kamerling
I M C
IM
Centre for Human Drug Research, Leiden, The Netherlands.
Van Haarst
A D
AD
De Kam
M L
ML
Cohen
A F
AF
Masclee
A A M
AA
Burggraaf
J
J
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004415:Dyspepsia / Q000188:drug therapy*; D005260:Female; D005704:Gallbladder / Q000000981:diagnostic imaging / Q000187:drug effects*; D005765:Gastrointestinal Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009037:Motilin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012189:Retrospective Studies; D014463:Ultrasonography
D015415:Biomarkers; D005765:Gastrointestinal Agents; D009037:Motilin