IngentaConnect Dose-related effects of motilin on proximal gastrointestinal moti...

Authors: Kamerling, I. M. C.¹; Van Haarst, A. D.¹; Burggraaf, J.¹; Schoemaker, H. C.¹; Biemond, I.²; Jones, R.³; Cohen, A. F.¹; Masclee, A. A. M.²

Source: Alimentary Pharmacology & Therapeutics, Volume 16, Number 1, January 2002 , pp. 129-135(7)

Publisher: Blackwell Publishing

Abstract:

Aim:

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.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.min/kg were equally effective.

Document Type: Research article

DOI: 10.1046/j.1365-2036.2002.01142.x

Affiliations: 1: Centre for Human Drug Research, Leiden, The Netherlands, 2: Leiden University Medical Centre, Department of Gastroenterology, Leiden, The Netherlands, 3: R. W. Johnson Pharmaceutical Research Institute, High Wycombe, UK

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Dose-related effects of motilin on proximal gastrointestinal motility