Ja. Sutton et al., THE CLINICAL-PHARMACOLOGY OF SINGLE DOSES OF OTILONIUM BROMIDE IN HEALTHY-VOLUNTEERS, European Journal of Clinical Pharmacology, 52(5), 1997, pp. 365-369
Objective: Otilonium is a smooth muscle spasmolytic with greater affin
ity for receptors in the smooth muscle of distal than proximal gut in
rats. This study was the first to compare distal and proximal GI trans
it effects in human subjects. Methods: Using an increasing dose design
for the safe exploration of clinical and supraclinical single dose le
vels, two groups of eight volunteers received either 40, 120 and 200 m
g or 80, 160 and 240 mg otilonium. Gastric emptying of 400 mi 10% gluc
ose solution was assessed by epigastric impedance (EI), orocaecal tran
sit time (OCTT) by the lactulose breath-hydrogen method and whole gut
transit time (WGTT) by the method of Hinton et al. [1]. Potential anti
cholinergic effects were assessed via visual accommodation using the R
AF rule and saliva flow in response to sucking a sweet. Results: Media
n WGTT after 120 mg significantly increased by 4.1 h relative to place
bo, but at higher doses median changes relative to placebo were not si
gnificant due to wide increases in group variance. The EI t50% was del
ayed by 1.4 min when results from the two highest doses were combined
and compared with placebo; this small difference was statistically sig
nificant but seems unlikely to achieve physiological or clinical signi
ficance. OCTT, visual accommodation and saliva flow were unaltered. Ot
ilonium bromide was well tolerated at all doses, due mainly to low sys
temic absorption.