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

Adil Eddie Bharucha, H. Isowa, S. Hiro, Z. Guan

Research output: Contribution to journalArticle

3 Citations (Scopus)

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)
JournalNeurogastroenterology and Motility
Volume25
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Gastrointestinal Transit
Muscarinic Antagonists
Placebos
Gastric Emptying
Hardness
Sample Size
Muscarinic M3 Receptors
fesoterodine
Overactive Urinary Bladder
Solifenacin Succinate
Random Allocation
Radionuclide Imaging
Habits

Keywords

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

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Gastroenterology
  • Physiology

Cite this

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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 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).",
keywords = "Adult, Female, Fesoterodine, Gastroin-testinal transit, Randomized controlled trial, Solifenacin",
author = "Bharucha, {Adil Eddie} and H. Isowa and S. Hiro and Z. Guan",
year = "2013",
month = "1",
doi = "10.1111/nmo.12043",
language = "English (US)",
volume = "25",
journal = "Neurogastroenterology and Motility",
issn = "1350-1925",
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TY - JOUR

T1 - Differential effects of selective and non-selective muscarinic antagonists on gastrointestinal transit and bowel function in healthy women

AU - Bharucha, Adil Eddie

AU - Isowa, H.

AU - Hiro, S.

AU - Guan, Z.

PY - 2013/1

Y1 - 2013/1

N2 - 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).

AB - 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).

KW - Adult

KW - Female

KW - Fesoterodine

KW - Gastroin-testinal transit

KW - Randomized controlled trial

KW - Solifenacin

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U2 - 10.1111/nmo.12043

DO - 10.1111/nmo.12043

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C2 - 23171069

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