Human urine with solifenacin intake but not tolterodine or darifenacin intake blocks detrusor overactivity

Abstract

The objective of the study was to evaluate the local effects of three antimuscarinics excreted into human urine after oral ingestion. Two normal adult collected their voided urine after taking oral doses of tolterodine, darifenacin, and solifenacin for 7 days with a 14-day washout period. The urodynamic effect of intravesically administered human urine on carbachol-induced bladder overactivity was studied in female rats. Cystometric parameters were measured during continuous infusion of saline and human urine and then a mixture of carbachol (30 microM) and human urine. Carbachol significantly reduced the intercontraction interval and bladder capacity in the control (urine taken in the absence of oral antimuscarinics) and tolterodine- or darifenacin-administered groups. However, human urine obtained after taking solifenacin prevented the carbachol-induced detrusor overactivity. Urine excreted after oral ingestion of solifenacin provides a localized pharmacological advantage for the treatment of the overactive bladder syndrome.

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Ameliorative Effect of Solifenacin Succinate (Vesicare®), a Bladder-Selective Antimuscarinic Agent, on Overactive Bladder Symptoms, Especially Urgency Episodes

“…Intravenous solifenacin has been reported to reduce the bladder afferent activity with the measurement of pelvic nerve spikes in rats (20). In addition, bladder instillation of carbachol induced decreases in bladder capacity, and intravesical human urine obtained after administration of solifenacin prevented carbacholinduced decreases in bladder capacity (21). In contrast, intravesical human urine obtained after administration of tolterodine and darifenacin showed no effect on bladder function.…”

Muscarinic Receptor Binding in Rat Bladder Urothelium and Detrusor Muscle by Intravesical Solifenacin

“…Chuang et al showed that human urine obtained after taking solifenacin (5 mg) prevented the carbachol-induced detrusor overactivity. 18) Thus, the urine excreted after oral ingestion of solifenacin may provide a localized pharmacological advantage for the treatment of overactive bladder syndrome. The current study aimed to examine such hypothesis by measuring muscarinic receptor binding in the bladder urothelium and detrusor muscles of rats after intravesical instillation of solifenacin.…”

Phase 1 Clinical Trial of Vesicare™ (Solifenacin) in the Treatment of Urinary Incontinence After Radical Prostatectomy

“…25 A potential unique benefit of solifenacin among anticholinergics is that it is more selective than other antimuscarinics and has up to 15% of the medication secreted as an active metabolite into the urine and available for binding to receptors on the urothelium. 26,27 If incontinence does occur, then the active metabolite may potentially bind the urethral urothelium causing less irritation and decreasing the signals sent to the bladder causing instability. In addition, solifenacin did perform better than tolterodine ER in the European STAR trial, decreasing number of incontinence pads used, in which 14.7% were men.…”