Rovner Eric S
Department of Urology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Drugs. 2004;64(21):2433-46. doi: 10.2165/00003495-200464210-00005.
Trospium chloride is an orally active, quaternary ammonium compound with antimuscarinic activity. It binds specifically and with high affinity to muscarinic receptors M(1), M(2) and M(3), but not nicotinic, cholinergic receptors. It is hydrophilic and does not cross the normal blood-brain barrier in significant amounts and, therefore, has minimal central anticholinergic activity. Peak plasma trospium chloride concentrations are attained approximately 5-6 hours after oral administration, which should occur before meals as concurrent food ingestion significantly reduces trospium bioavailability. Trospium chloride undergoes negligible metabolism by the hepatic cytochrome P450 system; few metabolic drug interactions are known. While trospium chloride dosage adjustments based on age or sex appear unwarranted, such adjustments may be needed in patients with severe renal impairment. Direct comparative studies in patients with overactive bladder indicate that trospium chloride is at least as effective as oxybutynin and tolterodine. Placebo-controlled studies have also confirmed the efficacy of trospium chloride in terms of improved urodynamic parameters; small-scale, noncomparative studies have documented significant trospium chloride-induced improvements in patients with reflex neurogenic bladder, postoperative bladder irritation and radiation-induced cystitis; and observational studies including >10,000 patients have also revealed favourable findings for trospium chloride, including a marked decrease in incontinence episodes and substantial improvement in health-related quality of life. Trospium chloride is generally well tolerated, and significantly more so than immediate-release oxybutynin. The most frequent adverse events, occurring in >1% of trospium chloride-treated patients, are dry mouth, dyspepsia, constipation, abdominal pain and nausea. Available for many years in several countries outside North America, trospium chloride is likely to develop an important role in the management of overactive bladder following its approval in the US on 28 May 2004.
氯化托烷司琼是一种具有抗毒蕈碱活性的口服活性季铵化合物。它能特异性且高亲和力地与毒蕈碱受体M(1)、M(2)和M(3)结合，但不与烟碱型胆碱能受体结合。它具有亲水性，不会大量穿过正常的血脑屏障，因此中枢抗胆碱能活性极小。口服给药后约5 - 6小时达到血浆氯化托烷司琼浓度峰值，应在饭前服用，因为同时摄入食物会显著降低托烷司琼的生物利用度。氯化托烷司琼经肝脏细胞色素P450系统代谢的量可忽略不计；已知的药物代谢相互作用很少。虽然基于年龄或性别调整氯化托烷司琼剂量似乎没有必要，但严重肾功能损害患者可能需要进行此类调整。对膀胱过度活动症患者的直接比较研究表明，氯化托烷司琼至少与奥昔布宁和托特罗定一样有效。安慰剂对照研究也证实了氯化托烷司琼在改善尿动力学参数方面的疗效；小规模、非对照研究记录了氯化托烷司琼对反射性神经源性膀胱、术后膀胱刺激和放射性膀胱炎患者有显著改善；包括超过10000名患者的观察性研究也显示了氯化托烷司琼的有利结果，包括失禁发作显著减少和健康相关生活质量大幅改善。氯化托烷司琼一般耐受性良好，且比速释奥昔布宁耐受性明显更好。在接受氯化托烷司琼治疗的患者中，发生率超过1%的最常见不良事件是口干、消化不良、便秘、腹痛和恶心。氯化托烷司琼在北美以外的几个国家已上市多年，2004年5月28日在美国获批后可能会在膀胱过度活动症的治疗中发挥重要作用。
