Synergistic Effect by Co-Administration of Tamsulosin and Solifenacin on Bladder Activity in Rats.

Abstract

We examined the effects of alpha1-adrenoceptor antagonist (tamsulosin hydrochloride) and antimuscarinic agent (solifenacin succinate) alone or in combination on the urinary adenosine triphosphate (ATP) level and cystometric parameters before and after bladder stimulation. Female rats were administered tamsulosin hydrochloride (0.5 or 3 µg/kg/h) and/or solifenacin succinate (20 or 100 µg/kg/h) via a subcutaneously implanted osmotic minipump. Rats receiving distilled water were used as control. After 2 weeks, continuous cystometry with physiological saline or 0.1% acetic acid solution was performed. Urinary ATP level was also measured before and after stimulation by 0.1% acetic acid solution. During cystometry with bladder stimulation, the interval between voiding became shorter and the maximum voiding pressure (MVP) became higher in the control group. In the high-dose tamsulosin and solifenacin groups, the inhibition of urinary frequency was observed. The MVP also became higher in the high-dose tamsulosin group, but such a change was not seen in the high-dose solifenacin group. In case of low-dose administration, either agent alone did not inhibit the increase of urinary frequency and MVP due to bladder stimulation. However, co-administration of these ineffective low doses of tamsulosin and solifenacin resulted in the inhibition of urinary frequency. The high-dose or low-dose solifenacin group and the co-administration group showed similar inhibition of the increase of urinary ATP after bladder stimulation. Tamsulosin may have a different effect on the bladder and/or the neuronal pathways that is unrelated to ATP, so the combination of tamsulosin and solifenacin may synergistically inhibit urinary frequency after bladder stimulation.