Pharmacokinetic profile of tamsulosin OCAS

The tamsulosin oral‐controlled absorption system (OCAS®) is a new tablet formulation of the α₁‐adrenoceptor (α₁‐AR) antagonist tamsulosin, which is used for treating lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). The tablet uses the OCAS technology, which was specifically designed to give a more continuous 24‐h release of tamsulosin, resulting in a more consistent and continuous 24‐h plasma concentration, a lower maximum plasma concentration (C_max) and an independence of pharmacokinetics (PKs) on food intake. It was expected that the improved PK profile would translate into a better control of day‐ and night‐time symptoms of BPH and a lower risk of adverse events. Phase I PK studies showed that tamsulosin OCAS indeed has a flattened PK profile with a lower C_max and a more stable and consistent 24‐h concentration of tamsulosin, independent of food intake, compared to conventional tamsulosin. A study combining γ‐scintigraphy and PK analysis of blood samples confirmed that the improved PK profile of tamsulosin OCAS is attributed to the tablet being consistently and continuously released throughout the entire gastrointestinal tract, including the colon.     

Outcomes and complications of naftopidil versus tamsulosin for elderly men with lower urinary tract symptoms secondary to benign prostatic hyperplasia: A systematic review and meta-analysis

We conducted a systematic review and meta-analysis to assess the outcomes and complications of naftopidil in treating elderly men with lower urinary tract symptoms secondary to benign prostatic hyperplasia and compared them with those administered with tamsulosin. A literature review was performed to identify the available randomised controlled trials concerning the comparison between naftopidil and tamsulosin for men with LUTS/BPH. We searched the following databases: the Cochrane Library Database, PubMed, Embase and Web of Science. Eleven publications involving 1,114 men (557 in the naf group and 557 in the tam group) were pooled in our analysis. We found no significant differences in the total IPSS, IPSS storage score, IPSS voiding score, quality of life index, peak urinary flow rate, average flow rate and post-void residual volumes. We assessed cardiovascular and sexual adverse events, acute urinary retention, surgical intervention, withdrawals due to any reason and withdrawals due to adverse events. The incidence of adverse events was similar among patients in naf and tam groups. In conclusion, naftopidil shared comparable efficacy and similar incidence of adverse events with tamsulosin and appears to be a promising agent for and alternative to tam. However, more prospective trials with high quality and long-term treatment duration are needed to verify this observation.     

盐酸坦索罗辛联合吲哚美辛栓治疗输尿管下段结石的初步研究

目的评价盐酸坦索罗辛与吲哚美辛栓联合治疗输尿管下段结石的临床疗效。方法 89例确诊为单纯输尿管下段结石(结石均小于8mm)的患者,随机分为三组:试验组,口服盐酸坦索罗辛(0.4mg/d)和吲哚美辛栓0.1g塞肛,1次/d;对照组1,口服中药排石颗粒4g/次,2次/d;对照组2,口服盐酸坦索罗辛0.4mg,1次/d;观察结石排出率、排出时间、肾绞痛发生率、药物不良反应发生率、干预治疗率等。结果试验组结石排出率为90.63%(29/32),对照组1和对照组2结石排除率分别为42.31%(11/26)和70.97%(22/31),试验组与对照组1比较,试验组与对照组2比较,两个对照组比较,差异均有统计学意义(χ2分别=4.76、3.94、15.65;P均<0.05)。试验组的结石排出时间为(8.73±2.15)d,对照组1和对照组2结石排出时间分别为(12.31±1.52)d和(9.52±1.61)d,试验组与对照组1比较,试验组与对照组2比较,两个对照组比较,差异均有统计学意义(t分别=6.77、-1.70、-7.35;P均<0.05)。试验组、对照组1、照组2的肾绞痛发生率分别为31.25%(10/32)、63.28%(17/26)、45.16%(14/31),试验组和对照组2以及对照组1和对照组2比较,差异均无统计学意义(χ2分别为1.29、2.33,P均>0.05);试验组和对照组1比较,差异有统计学意义(χ2=8.24,P<0.05)。三组患者均未发生严重的药物不良反应(χ2分别=0.33、0.23、0.35,P均>0.05)。结论联合应用盐酸坦索罗辛和吲哚美辛栓治疗输尿管下段结石安全、副作用小,能明显提高排石率,缩短排石时间,并能减少镇痛药物的应用。     

Efficacy and safety of solifenacin plus tamsulosin oral controlled absorption system in men with lower urinary tract symptoms: a meta-analysis

We performed a meta-analysis to compare treatment with a combination of solifenacin plus tamsulosin oral controlled absorption system (TOCAS) with placebo or TOCAS monotherapy. The aim of the meta-analysis was to clarify the efficacy and safety of the combination treatments method for lower urinary tract symptoms (LUTS). We searched for trials of men with LUTS that were randomized to combination treatment compared with TOCAS monotherapy or placebo. We pooled data from three placebo-controlled trials meeting inclusion criteria. Primary outcomes of interest included changes in International Prostate Symptom Score (IPSS) and urinary frequency. We also assessed postvoid residual, maximum urinary flow rate, incidence of urinary retention (UR), adverse events. Data were pooled using random or fixed effect models for continuous outcomes and the Mantel–Haenszel method to generate risk ratio. Reductions in IPSS storage subscore and total urgency and frequency score (TUFS) were observed with solifenacin 6 mg plus TOCAS compared with placebo (P < 0.0001 and P < 0.0001, respectively). Reductions in IPSS storage subscore and TUFS were observed with solifenacin 9 mg plus TOCAS compared with placebo (P = 0.003 and P = 0.0006, respectively). Reductions in TUFS was observed with solifenacin 6 mg plus TOCAS compared with TOCAS (P = 0.01). Both combination treatments were well tolerated, with low incidence of UR. Solifenacin 6 mg plus TOCAS significantly improved total IPSS, storage and voiding symptoms compared with placebo. Solifenacin 6 mg plus TOCAS also improved storage symptoms compared with TOCAS alone. There was no additional benefit of solifenacin 9 mg compared with 6 mg when used in combination with TOCAS.     

Effects of α1-adrenergic receptor antagonists on the development and progression of urothelial cancer

We recently demonstrated that silodosin, a selective α₁-blocker often prescribed for the symptomatic treatment of benign prostatic hyperplasia (BPH), could inactivate a c-fos proto-oncogene regulator ELK1 in bladder cancer cells possessing a functional androgen receptor (AR). However, the clinical impact of α₁-blockers on the development and progression of bladder cancer remained poorly understood. In the present study, we investigated if α₁-blockers clinically used, including silodosin, tamsulosin, and naftopidil, could prevent the neoplastic/malignant transformation and cell growth, using non-neoplastic urothelial SVHUC sublines with carcinogen/MCA challenge and bladder cancer lines, respectively. Bladder cancers in men treated with silodosin, tamsulosin, or naftopidil for their BPH were then compared. Silodosin at 1-10 µM significantly inhibited the neoplastic transformation of MCA-SVHUC-AR cells, but not that of AR-negative MCA-SVHUC-control cells. In MCA-SVHUC-AR, silodosin significantly reduced the expression levels of oncogenes (c-fos/NF-κB1) and induced those of tumor suppressors (p27/PTEN). However, tamsulosin (up to 1 µM) or naftopidil (up to 10 µM) failed to significantly inhibit the neoplastic transformation of AR-positive or AR-negative urothelial cells. Similarly, cell proliferation/migration of AR-positive bladder cancer lines was considerably inhibited only by silodosin. Meanwhile, the incidence of bladder cancer in patients with silodosin [49/540 (9.1%)] was marginally lower, compared to those with tamsulosin [64/523 (12.2%); P=0.094] or tamsulosin or naftopidil [64+28/523+236 (12.1%); P=0.082]. There were no significant differences in tumor grade/stage among the 3 cohorts. Outcome analysis revealed lower risks for disease progression of non-muscle-invasive bladder tumors in the silodosin group than in the naftopidil group (P=0.011) or tamsulosin+naftopidil groups (P=0.035). Similarly, silodosin patients with muscle-invasive tumor had lower risks for disease progression, compared with tamsulosin (P=0.006) or tamsulosin+naftopidil (P=0.028) patients. Multivariate analysis further showed that silodosin treatment in those with non-muscle-invasive tumor was associated with improved progression-free survival, compared with naftopidil (hazard ratio=0.086; 95% confidence interval=0.008-0.905; P=0.041) or tamsulosin/naftopidil (hazard ratio=0.128; 95% confidence interval=0.016-1.036; P=0.054) treatment. Our in vitro studies thus indicate that both urothelial tumorigenesis and tumor growth are inhibited by silodosin, but not by tamsulosin or naftopidil. Clinical data further suggest that even pharmacological doses (e.g. 0.1 µM) of silodosin contribute to preventing bladder cancer progression.     

舍曲林联合盐酸坦索罗辛结合行为疗法治疗早泄

目的探讨联合应用舍曲林和盐酸坦索罗辛结合行为疗法治疗早泄的临床疗效。方法选择无器质性病变的早泄患者40例,随机分成2组,对照组予单纯行为疗法,治疗组予舍曲林和盐酸坦索罗辛结合行为疗法治疗。比较2组治疗前后的平均阴道内射精潜伏期、国际勃起功能指数(IIEF)问卷中的性交满意度评分,并评估在疗程结束时,患者及其配偶对性生活的满意程度。结果治疗组患者治疗后平均阴道内射精潜伏期以及IIEF问卷中的性交满意度评分均显著增加;治疗结束时,治疗组平均阴道内射精潜伏期(4.60±0.15)min,对照组(1.86±0.16)min;IIEF问卷中治疗组患者及配偶性交满意度评分比对照组有明显提高。2组比较均有显著性差异(P均<0.01)。结论舍曲林和盐酸坦索罗辛联合行为疗法是治疗早泄的一种有效方法。     

坦索罗辛联合索利那新在治疗轻中度良性前列腺增生合并膀胱过度活动症中的疗效分析

目的:探讨坦索罗辛联合索利那新在治疗轻中度BPH合并膀胱过度活动症(OAB)中的有效性及安全性。方法:选取在我院诊治的轻中度良性BPH合并OAB患者166例,分为轻度梗阻症状组(88例)(联合用药组48例及坦索罗辛组40例)和中度梗阻症状组(78例)(联合用药组36例及坦索罗辛组42例)。坦索罗辛组均服用坦索罗辛0.2mg,每日1次。联合用药组均口服坦索罗辛0.2mg,每日1次,索利那新5mg,每日1次,共12周。比较两组治疗前后国际前列腺症状评分(IPSS)、排尿期症状评分、储尿期症状评分、最大尿流率(Qmax)、残余尿量、膀胱过度活动症症状评分(OABSS)、尿常规检查、不良事件等。结果:在轻度梗阻症状组中,联合用药组治疗后在IPSS、储尿期症状评分、Qmax、OABSS明显优于治疗前(P0.05),而残余尿无明显变化(P0.05),坦索罗辛组治疗后仅IPSS较治疗前有所改善,而其他方面无明显变化(P0.05);而治疗后联合用药组IPSS[(9.7±3.0)分vs(15.8±3.3)分]、储尿期症状评分[(8.1±1.7)分vs(12.3±3.1)分]、Qmax[(18.6±4.1)ml/s vs(14.2±2.3)ml/s]、OABSS[(5.3±1.3)分vs(9.7±2.7)分]等方面明显优于坦索罗辛组(P均0.05),而残余尿、尿常规检查及不良事件无明显差异(P0.05);在中度梗阻症状组,联合用药组治疗后IPSS、排尿期症状评分、Qmax、OABSS明显优于治疗前,而残余尿无明显差异;坦索罗辛组治疗后IPSS、排尿期症状评分、Qmax、OABSS及残余尿较治疗前改善明显;联合用药组的OABSS优于坦索罗辛组[(4.8±1.5)分vs(6.5±2.5)分,P0.05],而在IPSS、Qmax、排尿期症状评分、尿常规检查及不良事件等方面与坦索罗辛组无明显差异(P均0.05)。结论:坦索罗辛联合索利那新在治疗BPH轻中度梗阻症状合并OAB均有明显疗效,其疗效优于单用坦索罗辛,而不良反应无明显增加。