Drug forecast--solifenacin: an investigational anticholinergic for overactive bladder

To review a new anticholinergic for overactive bladder undergoing review by the U.S. Food and Drug Administration, solifenacin.

A MEDLINE/PUBMED search was conducted to identify pertinent studies in the English language. In addition, proceedings of meetings of the Incontinence Society, European Association of Urology, American Urological Association, and American College of Obstetrics and Gynecology were reviewed for relevant abstracts. Additional references were obtained from the bibliographies of these sources. Data over the time period of 1986 through October 2003 were reviewed.

All studies evaluating any aspect of solifenacin in animals and humans.

Preclinical studies demonstrated that solifenacin was an antagonist at muscarinic cholinergic M1, M2, and M3 receptors. On the basis of comparative preclinical studies evaluating the effects of solifenacin and oxybutynin on guinea pig detrusor muscle cells, mouse submandibular gland cells, and the intact rat, solifenacin was felt to be a "uroselective" antimuscarinic. Solifenacin is predominantly eliminated via metabolism, with urinary excretion of parent compound being less than 10%. Solifenacin, dosed once daily, is significantly superior to placebo in reducing the number of micturitions, urge episodes, and urge incontinence episodes per day and increasing the volume voided per micturition. In two active-controlled trials, solifenacin was at least equivalent to tolterodine in efficacy and tolerability. The most problematic adverse effects of solifenacin are the anticholinergic effects of dry mouth, blurred vision, and constipation.

Although promising in preclinical studies, the uroselectivity of the anticholinergic activity of solifenacin has not been validated in clinical trials. No comparative efficacy/tolerability data with oxybutynin are available. On the basis of available data, solifenacin does not appear to be a substantial advance upon existing anticholinergics in the management of overactive bladder.