Aims of Study.

Both tolterodine (TOL) and controlled-release oxybutynin (OXY-XL) have been separately shown to be effective in the treatment of overactive bladder.  Both OXY-XL and TOL have been shown to be associated with less dry mouth than conventional immediate-release oxybutynin (IR-OXY); however, these treatments have not been directly compared in a controlled study. Saliva output studies following all three treatments have been separately reported but differences in study methodology prevent comparison across studies. This is the first study that objectively evaluates dry mouth as measured by saliva output following the three medications and placebo.

Methods.

This was a randomized, double-blind, four-treatment, four-period, crossover study.  The four treatments were single doses of OXY-XL (10 mg), IR-OXY (5 mg), TOL (2 mg), and placebo, with a 5-7 day washout period between treatments. Saliva output (stimulated by chewing parafilm) was collected in a beaker over a 2-minute period at 1 to 2 hour intervals for 12 hours after dosing.  Saliva output integrated as area under the curve (AUC) and the lowest saliva value production (TROUGH) over the 12-h period was estimated.

 

Results.

All three medications resulted in significantly lower saliva AUC compared to placebo. OXY-XL and TOL were similar with respect to saliva AUC but significantly higher than IR-OXY (Table 1 & 2).  All three medications also resulted in significantly lower saliva TROUGH compared to placebo. The lowest TROUGH value was observed with TOL followed by IR-OXY, OXY-XL and placebo (Table 1). 

 

Table 1: Mean (SD) Saliva Production Parameters
Saliva Parameter	OXY-XL	TOL	IR-OXY	Placebo
AUC (g.h)	30 (15)	29 (17)	27 (15)	33 (17)
TROUGH (g/2min)	1.7 (1.0)	1.4 (0.9)	1.5 (0.9)	2.0 (1.1)
Table 2: Statistical Comparison (p-values)
Saliva Parameter	Active vs. Placebo	OXY-XL vs. IR-OXY	TOL  vs. IR-OXY	OXY-XL vs. TOL
AUC (g.h)	<0.01	0.01	0.005	0.80
TROUGH (g/2min)	<0.001	0.05	0.96	0.06

Conclusion.

This study showed that 10 mg controlled-release oxybutynin and 2 mg tolterodine appear to be similar with respect to dry mouth as measured by salivary output and associated with less dry mouth than 5 mg immediate-release oxybutynin.

Source of Funding: ALZA Corp. on behalf of Crescendo Pharmaceuticals Corp., Mountain View, CA.