Differential effects of selective and non-selective muscarinic antagonists on gastrointestinal transit and bowel function in healthy women
Article first published online: 21 NOV 2012
© 2012 Blackwell Publishing Ltd
Neurogastroenterology & Motility
Volume 25, Issue 1, pages e35–e43, January 2013
How to Cite
Bharucha, A. E., Isowa, H., Hiro, S. and Guan, Z. (2013), Differential effects of selective and non-selective muscarinic antagonists on gastrointestinal transit and bowel function in healthy women. Neurogastroenterology & Motility, 25: e35–e43. doi: 10.1111/nmo.12043
- Issue published online: 20 DEC 2012
- Article first published online: 21 NOV 2012
- Received: 1 June 2012 Accepted for publication: 18 October 2012
- gastroin-testinal transit;
- randomized controlled trial;
Background The gastrointestinal effects of antimuscarinic drugs used to treat overactive bladder may be related to the selectivity of these agents for M3-muscarinic receptor subtypes. We compared the effects of non-selective (fesoterodine) and M3-selective (solifenacin) antimuscarinics on gastrointestinal transit in healthy women.
Methods Gastric emptying (GE), small-intestinal transit (colonic filling at 6 h), colonic transit [geometric center at 24 h (GC24; primary endpoint) and 48 h (GC48)], and bowel habits were assessed by scintigraphy and bowel diaries before and after randomization to fesoterodine 8 mg, solifenacin 10 mg, or placebo (2 : 2 : 1) for 14 days. An interim analysis to finalize sample size was conducted.
Key Results After 60 subjects [placebo (n = 12), fesoterodine (n = 25), solifenacin (n = 23)] completed the study, the study was terminated due to a prespecified criterion (sample size ≥452.5 needed to provide ≥80% power to demonstrate superiority of fesoterodine over solifenacin in GC24). Compared with baseline, (i) placebo delayed small-intestinal, but not colonic, transit, (ii) fesoterodine significantly increased GE t1/2vs placebo (17.0 min; P = 0.027), and (iii) fesoterodine and solifenacin delayed small-intestinal (−36.8% and −21.8%, respectively, P < 0.001 vs placebo) and colonic transit (GC24: −0.44 and −0.49, respectively, P < 0.05 vs placebo; GC48: −0.25 and −0.65, respectively, P > 0.05 vs placebo). Solifenacin increased stool hardness from baseline (P = 0.010 for difference vs fesoterodine); stool frequency was comparable.
Conclusions & Inferences In healthy women, fesoterodine had greater effects on small-intestinal transit and solifenacin had greater effects on colonic transit; the latter finding may explain why solifenacin, but not fesoterodine, increased stool hardness. (ClinicalTrials.gov ID: NCT00892034).