Maniscalco Maria, Singh-Franco Devada, Wolowich William R, Torres-Colón Rolando
Nova Southeastern University, College of Pharmacy, Fort Lauderdale, Florida 33328, USA.
Clin Ther. 2006 Sep;28(9):1247-72. doi: 10.1016/j.clinthera.2006.09.017.
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.
This article reviews the current primary literature concerning the pharmacokinetics, efficacy, and tolerability of SOL in the treatment of OAB.
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.
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%).
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.
膀胱逼尿肌活动过度可导致尿急、尿频和尿失禁。抗毒蕈碱药物是首选治疗药物，因为它们可降低该肌肉的收缩性。琥珀酸索利那新（SOL）是一种竞争性毒蕈碱受体拮抗剂，于2004年末获美国食品药品监督管理局批准，用于治疗伴有急迫性尿失禁、尿急和尿频症状的膀胱过度活动症（OAB）。
本文综述目前关于SOL治疗OAB的药代动力学、疗效和耐受性的主要文献。
通过检索MEDLINE（1966年至2006年第4周）、EMBASE（1991年至2006年第一季度）、《临床医学当前目录》（2005年第10周 至2006年第9周）、Cochrane系统评价数据库、MICROMEDEX医疗保健系列以及《国际药学文摘》（1970年至今）来识别相关英文文章。检索词为膀胱过度活动症、尿失禁、索利那新、YM905、药代动力学和成本。
SOL具有高度脂溶性（在pH 7.0时辛醇与水的分配系数为50:1），口服生物利用度完全，蛋白结合率为98%。它通过细胞色素P450 3A同工酶代谢，约50%的剂量以母体化合物形式经肾脏排泄，还有1种活性代谢物和3种非活性代谢物。在两项为期12周的III期研究中，接受5或10 mg SOL治疗的患者与安慰剂组相比，每24小时的排尿次数（P≤0.01）、尿失禁发作次数（P≤0.05）和尿急发作次数（P≤0.01）均显著减少；每次排尿的尿量显著增加（P≤0.01）。在一项将5和10 mg SOL与托特罗定缓释片4 mg进行比较的研究中，两种药物均与每24小时排尿次数显著减少相关（分别为-2.45次和-2.24次；非劣效性P = 0.004）。在一项对两项为期12周研究的汇总数据进行的研究中，接受5或10 mg SOL治疗的患者在多个生活质量领域有显著改善（P≤0.05）。在4项研究的汇总分析中，接受5 mg（n = 266）和10 mg（n = 612）SOL治疗的患者中最常见的不良反应（在任何组中发生率≥3%）为口干（分别为10.9%和27.1%）、便秘（5.3%和12.9%）以及视力模糊（4.5%和4.7%）。
在所综述的研究中，SOL对治疗伴有急迫性尿失禁的OAB有效。不良反应包括口干、便秘和视力模糊。需要进一步研究以确定SOL在肝或肾功能损害患者中的疗效和耐受性。
