Solifenacin succinate for the treatment of symptoms of overactive bladder.
BACKGROUND
Overactivity of the bladder detrusor muscle can result in urinary urgency, frequency, and incontinence. Antimuscarinic agents are the treatment of choice, as they reduce the contractility of this muscle. Solifenacin succinate (SOL) is a competitive muscarinic-receptor antagonist approved by the US Food and Drug Administration in late 2004 for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency.


OBJECTIVE
This article reviews the current primary literature concerning the pharmacokinetics, efficacy, and tolerability of SOL in the treatment of OAB.


METHODS
Pertinent English-language articles were identified through a search of MEDLINE (1966-week 4, 2006), EMBASE (1991-first quarter of 2006), Current Contents/Clinical Medicine (week 10, 2005-week 9, 2006), the Cochrane Database of Systematic Reviews, MICROMEDEX Healthcare Series, and International Pharmaceutical Abstracts (1970-present). The search terms were overactive bladder, urinary incontinence, solifenacin, YM905, pharmacokinetics, and cost.


RESULTS
SOL is highly lipophilic (50:1 octanol:water distribution at pH 7.0), completely orally bioavailable, and 98% protein bound. It is metabolized by the cytochrome P450 3A isozyme, and approximately 50% of a dose is eliminated renally as parent compound, with 1 active and 3 inactive metabolites. In two 12-week Phase III studies, patients receiving SOL 5 or 10 mg had significant reductions compared with placebo in the numbers of voids (P < or = 0.01), incontinence episodes (P < or = 0.05), and urgency episodes (P < or = 0.01) per 24 hours; the volume voided per micturition was significantly increased (P < or = 0.01). In a study that compared SOL 5 and 10 mg with tolterodine extended release 4 mg, both agents were associated with significant reductions in the number of voids per 24 hours (-2.45 and -2.24 episodes, respectively; P = 0.004 for noninferiority). In a study of pooled data from two 12-week studies, patients who received SOL 5 or 10 mg reported significant improvements in a number of quality-of-life domains (P < or = 0.05). In a pooled analysis of 4 studies, the most common adverse effects (occurring in > or =3% of any group) in patients receiving SOL 5 mg (n = 266) and 10 mg (n = 612) were dry mouth (10.9% and 27.1%, respectively), constipation (5.3% and 12.9%), and blurred vision (4.5% and 4.7%).


CONCLUSIONS
In the studies reviewed, SOL was effective in the treatment of OAB with urge incontinence. Adverse effects included dry mouth, constipation, and blurred vision. Further studies are needed to determine the efficacy and tolerability of SOL in patients with hepatic or renal impairment.
Maniscalco
Maria
M
Nova Southeastern University, College of Pharmacy, Fort Lauderdale, Florida 33328, USA.
Singh-Franco
Devada
D
Wolowich
William R
WR
Torres-Colón
Rolando
R
D002986:Clinical Trials as Topic; D006801:Humans; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D011812:Quinuclidines / Q000627:therapeutic use*; D000069464:Solifenacin Succinate; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000503:physiopathology; D014563:Urodynamics
D018727:Muscarinic Antagonists; D011812:Quinuclidines; D044005:Tetrahydroisoquinolines; D000069464:Solifenacin Succinate