Differential effects of selective and non‐selective muscarinic antagonists on gastrointestinal transit and bowel function in healthy women. Issue 1 (21st November 2012)

• Record Type: Journal Article
• Authors: Bharucha, A. E.; Isowa, H.; Hiro, S.; Guan, Z.
• Is Part Of: Neurogastroenterology & motility. Volume 25:Issue 1(2013:Jan.)
• Page Start: e35
• Page End: e43
• Publication Date: 2012-11-21
• Subjects: Gastrointestinal system -- Motility -- Periodicals; Gastrointestinal system -- Innervation -- Periodicals; 616.33
• DOI: 10.1111/nmo.12043
• Languages: English
• ISSNs: 1350-1925

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p> <bold>Background </bold> The gastrointestinal effects of antimuscarinic drugs used to treat overactive bladder may be related to the selectivity of these agents for M<sub>3</sub>‐muscarinic receptor subtypes. We compared the effects of non‐selective (fesoterodine) and M<sub>3</sub>‐selective (solifenacin) antimuscarinics on gastrointestinal transit in healthy women.</p> <p> <bold>Methods </bold> 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.</p> <p> <bold>Key Results </bold> After 60 subjects [placebo (<italic>n</italic> = 12), fesoterodine (<italic>n</italic> = 25), solifenacin (<italic>n</italic> = 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 <italic>t</italic><sub>1/2</sub><italic>vs</italic> placebo (17.0 min; <italic>P</italic> = 0.027), and (iii) fesoterodine and solifenacin delayed small‐intestinal (−36.8% and −21.8%, respectively, <italic>P </italic><<italic> </italic>0.001 vs placebo) and colonic transit (GC24: −0.44 and −0.49, respectively, <italic>P </italic><<italic> </italic>0.05 vs placebo; GC48: −0.25 and −0.65, respectively, <italic>P </italic>><italic> </italic>0.05 <italic>vs</italic> placebo). Solifenacin increased stool hardness from baseline (<italic>P</italic> = 0.010 for difference <italic>vs</italic> fesoterodine); stool frequency was comparable.</p> <p> <bold>Conclusions & Inferences </bold> 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).</p> </abstract>