Gender specificity of tolterodine on micturition and the diurnal variationof urine production of the conscious rat

Objective To evaluate the effect of the oral administration of tolterodine on the diurnal micturition characteristics of the male and female conscious rat, and to examine the relative effect of tolterodine in influencing wate r consumption and urine production. Materials and methods Baseline micturition volume and frequency characteris tics of nine male and 10 female Sprague-Dawley age-matched adult rats (body weight 399 +/- 15 and 249 +/- 3 g, respectively) were evaluated over 24-h. Initial hydration conditions were standardized with an oral dose (5 mL) of water. Rats were subsequently placed in a metabolic cage and had free acce ss to water. Micturition volume/frequency characteristics were derived from the measurements of voided volume (measured using a digital balance below the metabolic cage and connected to a computer). The total volume of water consumed over the 24 h was also measured. Two separate baseline studies wer e conducted, followed by the administration of a single oral dose of 1 mg/m L of tolterodine dissolved in 5 mL of water. The mean frequency of micturit ion and mean volume voided per micturition were computed in 3-h periods and plotted over the 24-h period. In addition, the mean values of the number o f micturitions and voided volumes during the day/dark cycle were evaluated. Results Baseline data showed that females (when corrected for body weight) consistently imbibed significantly more water (83%) than did male rats. Tol terodine did not significantly affect water consumption in the males but si gnificantly reduced water consumption in females by 42%. Tolterodine did no t significantly affect the amount of urine produced by male rats but signif icantly reduced the total amount of urine production in females by 26%. Tol terodine significantly increased the number of voids in male rats compared with baseline during the day but not during the night. More importantly tol terodine produce no significant effect on the volume voided per micturition in male rats either during the day or night cycle, but significantly decre ased the volume voided per micturition in females. Conclusions These results suggest that the effect of tolterodine on micturi tion is gender-specific, suppressing water consumption and urine production in female but not male rats, and decreasing bladder volume. There is a pos sibility that the reported clinical effects of tolterodine arise through th e suppression of fluid consumption.