A comparison of the effects on saliva output of oxybutynin chloride and tolterodine tartrate

Background: Oxybutynin chloride and tolterodine tartrate are anticholinergi c agents used to suppress involuntary bladder contractions in urinary incon tinence. They act by inhibiting binding of acetylcholine to the muscarinic receptors in the detrusor muscle of the bladder. The same types of muscarin ic receptors are found in the salivary glands; thus anticholinergic agents may decrease saliva production and cause dry mouth, a commonly cited reason for discontinuation of therapy. Objective: The primary objective of this study was to compare saliva output , which is an objective measure of dry mouth, in subjects taking immediate- or extended-release oxybutynin, tolterodine, or placebo. Methods: This was a single-site, single-dose, randomized, double-blind, 4-t reatment, LC-period crossover study. Subjects were randomly assigned to 1 o f 4 treatment sequences that included extended-release oxybutynin 10 mg, to lterodine 2 mg, immediate-release oxybutynin 5 mg, and placebo. Saliva outp ut was measured objectively before dosing with each treatment and at 0.5, 1 , 2, 3, 4, 6, 8, 10, and 12 hours after dosing. Results: Thirty-six healthy adult volunteers (22 women and 14 men) particip ated in the study. They ranged in age from 19 to 42 years (mean, 27 :years) . Thirty-one were white, 3 Asian, and 2 black. There: were no significant d ifferences in predose saliva output between the 4 study groups. With placeb o, saliva output increased throughout the day. Saliva output was maintained at predose levels throughout the day with extended-release oxybutynin. Two hours after dosing with tolterodine and immediate-release oxybutynin, sali va output decreased nearly 0.5 g in specimens collected over 2 minutes. All 3 active treatments were associated with lower saliva output compared with placebo. Extended-release oxybutynin and tolterodine were similar with res pect to area under the saliva concentration-time curve but were associated with significantly greater saliva output thanwas immediate-release oxybutyn in (P < 0.01). There were no serious adverse events (AEs) in this study. AE s were similar between treatments, although the incidence of headache was h igher in the active-treatment groups than with placebo. Conclusions: Objective assessment of saliva output in healthy adult volunte ers indicated that extended-release oxybutynin and tolterodine had less imp act on saliva output than did conventional immediate-release oxybutynin, su ggesting that they may yield lower levels of dry mouth.