The clinical pharmacology of single doses of otilonium bromide in healthy volunteers.
OBJECTIVE
Otilonium is a smooth muscle spasmolytic with greater affinity for receptors in the smooth muscle of distal than proximal gut in rats. This study was the first to compare distal and proximal GI transit effects in human subjects.


METHODS
Using an increasing dose design for the safe exploration of clinical and supraclinical single dose levels, two groups of eight volunteers received either 40, 120 and 200 mg or 80, 160 and 240 mg otilonium. Gastric emptying of 400 ml 10% glucose solution was assessed by epigastric impedance (EI), orocaecal transit time (OCTT) by the lactulose breath-hydrogen method and whole gut transit time (WGTT) by the method of Hinton et al. [1]. Potential anticholinergic effects were assessed via visual accommodation using the RAF rule and saliva flow in response to sucking a sweet.


RESULTS
Median WGTT after 120 mg significantly increased by 4.1 h relative to placebo, but at higher doses median changes relative to placebo were not significant due to wide increases in group variance. The EI t50% was delayed by 1.4 min when results from the two highest doses were combined and compared with placebo; this small difference was statistically significant but seems unlikely to achieve physiological or clinical significance. OCTT, visual accommodation and saliva flow were unaltered. Otilonium bromide was well tolerated at all doses, due mainly to low systemic absorption.
Sutton
J A
JA
Guildford Clinical Pharmacology Unit, Royal Surrey County Hospital.
Kilminster
S G
SG
Mould
G P
GP
D000065:Accommodation, Ocular / Q000187:drug effects; D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D010276:Parasympatholytics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012463:Saliva / Q000187:drug effects / Q000378:metabolism
D010276:Parasympatholytics; D000644:Quaternary Ammonium Compounds; C013934:octylonium