title: Differential effects of selective and non-selective muscarinic antagonists on gastrointestinal transit and bowel function in healthy women.
abstract: 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.
  
  
  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
  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.
authors.affiliation: Clinical and Enteric Neuroscience Translational and Epidemiological Research Program (C.E.N.T.E.R.), Mayo Clinic, Rochester, MN 55905, USA. bharucha.adil@mayo.edu
authors.forename: A E
authors.initials: AE
authors.lastname: Bharucha
authors.forename: H
authors.initials: H
authors.lastname: Isowa
authors.forename: S
authors.initials: S
authors.lastname: Hiro
authors.forename: Z
authors.initials: Z
authors.lastname: Guan
mesh_terms: D000293:Adolescent; D000328:Adult; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D011812:Quinuclidines / Q000494:pharmacology*; D000069464:Solifenacin Succinate; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D018727:Muscarinic Antagonists; D011812:Quinuclidines; D044005:Tetrahydroisoquinolines; C526675:fesoterodine; D000069464:Solifenacin Succinate