Differential effects of selective and non-selective muscarinic antagonists on gastrointestinal transit and bowel function in healthy women

A. E. Bharucha, H. Isowa, S. Hiro, Z. Guan

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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 6h), colonic transit [geometric center at 24h (GC24; primary endpoint) and 48h (GC48)], and bowel habits were assessed by scintigraphy and bowel diaries before and after randomization to fesoterodine 8mg, solifenacin 10mg, or placebo (2:2:1) for 14days. 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 (17.0min; 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).

Original languageEnglish (US)
Pages (from-to)e35-e43
JournalNeurogastroenterology and Motility
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

  • Adult
  • Female
  • Fesoterodine
  • Gastroin-testinal transit
  • Randomized controlled trial
  • Solifenacin

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

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