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Differential effects of selective and non‐selective muscarinic antagonists on gastrointestinal transit and bowel function in healthy women
Author(s) -
Bharucha A. E.,
Isowa H.,
Hiro S.,
Guan Z.
Publication year - 2013
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12043
Subject(s) - solifenacin , placebo , medicine , overactive bladder , gastroenterology , randomization , clinical endpoint , urology , randomized controlled trial , pathology , alternative medicine
Background The gastrointestinal effects of antimuscarinic drugs used to treat overactive bladder may be related to the selectivity of these agents for M 3 ‐muscarinic receptor subtypes. We compared the effects of non‐selective (fesoterodine) and M 3 ‐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 t 1/2 vs 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).