Article date: April 2004
By: Ingrid M. C. Kamerling, Aernout D. Van Haarst, Jacobus Burggraaf, Rik C. Schoemaker, Marieke L. De Kam, Hartmut Heinzerling, Adam F. Cohen, Ad A. M. Masclee, in Volume 57, Issue 4, pages 393-401
Aim
To assess the effects of the motilin receptor antagonist RWJ‐68023 on basal and motilin‐stimulated proximal gastric volume.
Methods
Eighteen healthy male volunteers received RWJ‐68023 in two different doses or placebo for 135 min. After 45 min, subjects received a motilin infusion for 90 min. Proximal gastric volume was measured with a barostat at constant pressure and during isobaric distensions. Abdominal symptoms were scored using visual analogue scales. Motilin and RWJ‐68023 concentrations were assessed by radioimmunoassay and liquid chromatography‐mass spectrometry, respectively.
Results
Both dosages of RWJ‐68023 were safe and well tolerated. The most common adverse events were of gastrointestinal origin. RWJ‐68023 did not affect basal proximal gastric volume, but the high‐dose RWJ‐68023 reduced the contractile effect of motilin on the stomach. This antagonizing effect of RWJ‐68023 was only significant (P = 0.014) during the distension procedure.
Conclusions
The RWJ‐68023 doses used in this study were selected to accomplish plasma concentrations that would block the motilin effect entirely. However, the antagonizing effect of RWJ‐68023 was partial and only present when the tonic condition of the stomach was modulated by motilin.
DOI: 10.1046/j.1365-2125.2003.02034.x
View this article