Dose-related effects of motilin on proximal gastrointestinal motility.
OBJECTIVE
To assess non-invasively the dose-response relations for the effects of exogenous motilin on antrum contraction frequency, gall-bladder volume and gastric myoelectrical activity.


METHODS
In a double-blind, randomized, placebo-controlled, five-way crossover study, 10 fasted healthy volunteers were infused intravenously with synthetic human motilin (0.5, 1, 2 and 4 pmol x min/kg) or placebo for 60 min. Gall-bladder volume and antrum contractions were assessed by ultrasonography and gastric myoelectrical activity by electrogastrography. Motilin concentrations were measured using a radioimmunoassay.


RESULTS
Baseline plasma motilin levels (60 pmol/L) were similar for all treatments. Motilin levels increased upon the start of infusion and rapidly returned to baseline after cessation of the infusion. At motilin doses of 2 and 4 pmol.min/kg, the antrum contraction frequency was significantly augmented, with maximum differences of two contractions per 2-min interval compared to placebo, while no changes in gastric myoelectrical activity were observed. Changes in gall-bladder volume were not significantly different for any of the motilin doses compared to placebo.


CONCLUSIONS
Motilin increased antrum contraction frequency, whereas no effect on gastric myoelectrical activity was observed. Antrum contraction frequency appears to be a useful biomarker for motilin efficacy, and motilin doses of 2 and 4 pmol x min/kg were equally effective.
Kamerling
I M C
IM
Centre for Human Drug Research, Leiden, The Netherlands. lkamerli@CHDR.nl
Van Haarst
A D
AD
Burggraaf
J
J
Schoemaker
H C
HC
Biemond
I
I
Jones
R
R
Cohen
A F
AF
Masclee
A A M
AA
D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004594:Electrophysiology; D005260:Female; D005704:Gallbladder / Q000033:anatomy & histology / Q000187:drug effects; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D008297:Male; D009037:Motilin / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011706:Pyloric Antrum / Q000187:drug effects / Q000502:physiology
D005765:Gastrointestinal Agents; D009037:Motilin