title: Effect of tolterodine on gastrointestinal transit and bowel habits in healthy subjects.
abstract: Clinical trials and observations suggest that constipation is an uncommon side effect of treating overactive bladder with the muscarinic receptor antagonist tolterodine. Because muscarinic antagonism inhibits gastrointestinal motor activity, we evaluated the effects of tolterodine on bowel habits, gastrointestinal and colonic transit in healthy subjects. In this double-blind study, 36 healthy subjects were randomized to tolterodine extended release (ER, 4 mg daily) or placebo for 6 days. Gastric emptying (GE), small bowel and colonic transit were assessed on days 4-6 by scintigraphy. Bowel habits were recorded by diaries. Tolterodine did not significantly affect half-time for GE (GE t(half)) [116 +/- 6 min (mean +/- SEM) for placebo vs 126 +/- 7 min for tolterodine], small bowel transit measured by colonic filling at 6 h (45 +/- 6% for placebo vs 36 +/- 6% for tolterodine) or the geometric center of colonic transit at 24 h (2.9 +/- 0.2 for placebo vs 2.6 +/- 0.3 for tolterodine). Subjects who received tolterodine had slightly fewer bowel movements (i.e. 1.34 +/- 0.1 stools per day for placebo vs 1.0 +/- 0.1 for tolterodine; P = 0.02 for treatment effect). Tolterodine did not significantly affect stool consistency or ease of defecation. At the therapeutic dose used to treat overactive bladder, tolterodine did not significantly affect gastrointestinal or colonic transit and had minor effects on bowel habits in healthy subjects. Further studies are necessary to elucidate whether these observations are explained by tolterodine effects at muscarinic receptors which stimulate and inhibit gastrointestinal motility.
authors.affiliation: Clinical and Enteric Neuroscience Translational and Epidemiological Research Program (CENTER), Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. bharucha.adil@mayo.edu
authors.forename: A E
authors.initials: AE
authors.lastname: Bharucha
authors.forename: B
authors.initials: B
authors.lastname: Seide
authors.forename: Z
authors.initials: Z
authors.lastname: Guan
authors.forename: C N
authors.initials: CN
authors.lastname: Andrews
authors.forename: A R
authors.initials: AR
authors.lastname: Zinsmeister
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D003248:Constipation / Q000139:chemically induced / Q000503:physiopathology; D003408:Cresols / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D003672:Defecation / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D005772:Gastrointestinal Transit / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010665:Phenylpropanolamine / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000068737:Tolterodine Tartrate; D053201:Urinary Bladder, Overactive / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D001559:Benzhydryl Compounds; D003408:Cresols; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate