Effect of nightly versus on-demand vardenafil on recovery of erectile function in men following bilateral nerve-sparing radical prostatectomy

BACKGROUND: To date, no data have been available from large, well-designed trials comparing on demand and nightly dosing of phosphodiesterase type 5 (PDE5) inhibitors on recovery of erectile function in postprostatectomy patients with erectile dysfunction (ED). OBJECTIVE: To investigate the effect of early postoperative dosing with vardenafil, administered either nightly or on demand, compared with placebo on recovery of erectile function in men with ED following bilateral nerve-sparing radical prostatectomy (NSRP) surgery. DESIGN, SETTING, AND PARTICIPANTS: A randomised, double-blind, double-dummy, multicentre, parallel group study conducted at 87 centres across Europe, Canada, South Africa, and the United States. For inclusion, patients had to be scheduled to undergo bilateral NSRP within 1 mo of screening and have a normal International Index of Erectile Function erectile function domain (IIEF-EF) score of >/=26 at screening. A total of 628 men, aged 18-64 yr, were randomised to treatment. Study design consisted of a 9-mo double-blind treatment period, a 2-mo single-blind washout period, and an optional 2-mo open-label period. INTERVENTION: Patients received placebo, nightly vardenafil, or on demand vardenafil. MEASUREMENTS: Primary outcome measure was the percentage of subjects with an IIEF-EF score of >/=22 after the 2-mo washout period. Secondary variables included mean per-patient success rates for Sexual Encounter Profile (SEP) questions 2 and 3. RESULTS AND LIMITATIONS: No statistically significant differences were observed among treatment groups in the proportion of patients with an IIEF-EF score of >/=22 or in SEP3 success rates after the washout period. On-demand vardenafil treatment resulted in significantly greater IIEF-EF scores and better SEP3 response rates than placebo over the entire treatment period. CONCLUSIONS: In this study of men with ED following bilateral NSRP, vardenafil was efficacious when used on demand, supporting a paradigm shift towards on demand dosing with PDE5 inhibitors in this patient group. TRIAL REGISTRATION: European clinical trials database (EudraCT; available at http://eudract.emea.europa.eu/). Trial registration number: 11336.     

The COUPLES-project: a pooled analysis of patient and partner treatment satisfaction scale (TSS) outcomes following vardenafil treatment

OBJECTIVE: To assess the influence of vardenafil on treatment satisfaction in men with erectile dysfunction (ED) and their female partners. PATIENTS AND METHODS: This was a pooled analysis of three randomized, double-blind, placebo-controlled, 12-week studies of flexible-dose vardenafil vs placebo, in men with ED for >/=6 months (n = 788) and their untreated female partners. Measures of efficacy included the Treatment Satisfaction Scale (TSS), International Index of Erectile Function, Erectile Function domain (IIEF-EF), and Sexual Encounter Profile (SEP) questions 2 and 3 (SEP-2, 'Were you able to insert your penis into your partner's vagina?'; and SEP-3, 'Did your erection last long enough for you to have sexual intercourse?'). In addition to the overall analysis, there was a subgroup analysis for potential moderators of response, e.g. whether patients who had undergone previous phosphodiesterase type 5 (PDE-5) treatment. RESULTS: At baseline, least-squares (LS) mean scores for all TSS domains were similar in the vardenafil and placebo groups. After 12 weeks of treatment, vardenafil significantly improved the LS mean score for all domains compared with placebo, among both patients and their female partners (P < 0.0001, 'last'-observation-carried- forward analysis). Absolute between- group differences in LS mean TSS scores (vardenafil - placebo) were: ease of erection (patients 23.4, partners 24.9), erectile function satisfaction (36.7 and 32.9), pleasure from sexual activity (23.0, 23.7), satisfaction with orgasm (27.6, 21.8), confidence to complete sexual activity (28.2, 32.5), and satisfaction with medication (37.4, 35.6). The benefits of vardenafil were greater in men who had undergone previous PDE-5-inhibitor treatment and men aged <45 years, while the overall pattern of benefit was similar in all examined subgroups. There were significant benefits with vardenafil in all other variables (IIEF-EF scores and positive response rates to SEP-2 and SEP-3). CONCLUSIONS: Vardenafil significantly improved treatment satisfaction in men with ED, and in their partners. The results provide further evidence of the validity of the TSS.     

Endothelial rehabilitation: the impact of chronic PDE5 inhibitors on erectile function and protein alterations in cavernous tissue of diabetic rats

BACKGROUND: Diabetic men generally have reduced efficacy with PDE-5 inhibitors (PDE5i) for the treatment of erectile dysfunction (ED). OBJECTIVE: To determine whether chronic vardenafil exposure alters cavernous protein expression predicting improved erectile function in diabetes. DESIGN: Forty-two adult male Sprague Dawley rats with streptozotocin-induced (50mg/kg IP) diabetes for 4 wk, were exposed to either vehicle or vardenafil for 6 wk. Assessments compared the impact of vardenafil given at 1h and 20 h to erectile function and cellular alterations and downstream translation of cavernous protein profiles were aimed. INTERVENTION: Vehicle or vardenafil 0.5mg/kg/day by oral gavage for 6 wk. MEASUREMENTS: Erectile function, penile tissue morphology, protein expression and surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI) protein profiling were determined. RESULTS AND LIMITATIONS: A significant increase of intracavernous pressure was seen in both treatment arms compared to diabetic rats not receiving vardenafil. Immunohistochemical staining showed improved endothelial and smooth muscle cell staining with chronic vardenafil use. Western blot analysis demonstrated increased endothelial cell eNOS and smooth muscle alpha-actin protein content. SELDI protein profiling showed enhanced proteins expression at molecular weights of 14.7, 20, 41.9, 66.2, and 83.9 kDa in the chronically treated vardenafil group. CONCLUSIONS: Vardenafil was effective in treating diabetic-induced ED with the greatest effect achieved through chronic dosing, with no additive effect measured with the final acute dose. Changes noted in the histology and protein expression indicate that vardenafil may have a protective effect in this disease state. This finding may serve as a basis for further work evaluating the utility of chronic vardenafil dosing in diabetic men.     

A randomised, placebo-controlled study to assess the efficacy of twice-daily vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia

INTRODUCTION: Benign prostatic hyperplasia (BPH) is associated with bothersome lower urinary tract symptoms (LUTS) and reduced patient quality of life (QoL). Phosphodiesterase (type) 5 (PDE5) inhibitors such as vardenafil are commonly used for the treatment of erectile dysfunction (ED), but have also been shown to improve the symptoms of BPH. This randomised, double-blind, placebo-controlled study investigated the effects of vardenafil on LUTS and QoL in men with BPH/LUTS, with or without concomitant ED. METHODS: Men aged 45-64 yr with BPH/LUTS and an International Prostate Symptom Score (IPSS) > or =12 were randomised to receive either 10mg vardenafil or placebo twice daily. LUTS were assessed with the use of two primary efficacy parameters, IPSS score and maximum urinary flow rate (Qmax), as well as postvoid residual (PVR) urine volume; ED was measured with the use of the erectile function (EF) domain score of the International Index of Erectile Function (IIEF-EF); and QoL was assessed with the Urolifetrade mark QoL-9 questionnaire. RESULTS: After 8 wk of treatment, there was a significant improvement in the IPSS total score in the vardenafil group compared with placebo (-5.9 and -3.6, respectively; p=0.0013). Nominally significant improvements in irritative and obstructive IPSS subscores (p=0.0017 and p=0.0081, respectively), EF (p=0.0001), and Urolife QoL-9 (p<0.0001) were also associated with vardenafil treatment. Qmax and PVR urine volume did not change significantly with treatment, although baseline values were already considered close to normal. Vardenafil was generally well tolerated, with most adverse events considered mild or moderate in severity. CONCLUSIONS: Vardenafil treatment significantly improved LUTS, EF, and QoL in men with BPH/LUTS. Vardenafil may be considered a promising treatment option for men with symptoms secondary to BPH.     

Efficacy and tolerability of vardenafil in Asian men with erectile dysfunction

Aim： To evaluate the efficacy and tolerability of vardenafil, a phosphodiesterase type-5 （PDE-5） inhibitor, in men of Asian ethnicity with erectile dysfunction （ED）. Methods： In this prospective, double-blind, multinational study, Asian men were randomized to receive vardenafil （10 mg） or placebo （4：1 ratio） for 12 weeks. The primary efficacy variables were the International Index of Erectile Function erectile function domain （IIEF-EF）, and Sexual Encounter Profile （SEP） questions related to penetration and intercourse completion. Significant mean improvements were required in all three measures to show positive benefits of vardenafil treatment. Secondary efficacy variables included the Global Assessment Question （GAQ） on erection improvement. Results： Least-squares mean baseline IIEF-EF domain scores （vardenafil 14.6, placebo 13.4） were consistent with moderate ED. After 12 weeks, vardenafil treatment was associated with significant increases from the baseline in IIEF-EF domain scores compared with the placebo （22.4 vs. 14.3; P 〈 0.001）. Vardenafil was associated with significant improvements from baseline in least squares （LS） mean success rates for SEP-2 （vardenafil 82.2 vs. placebo 43.6; P 〈 0.001） and SEP-3 （vardenafil 66.1 vs. placebo 24.0; P 〈 0.001）. Positive GAQ responses were reported by 81.8% of vardenafil recipients vs. 24.3% of placebo recipients. Adverse events were reported by 25.4% of the vardenafil group, the majority mild and transient. Conclusion： Vardenafil （10 mg） is a highly effective and well-tolerated treatment for moderate ED in Asian men. These results add to the increasing amount of data demonstrating the safety and efficacy of vardenafil for the treatment of ED in a range of patient populations.     

应用新的治疗满意度量表来评估ED患者及其性伴侣对伐地那非治疗的满意度

治疗满意度量表(TSS)是为评估男性勃起功能障碍(ED)患者及其性伴侣对ED治疗的满意度而制订的一个新量表。该自我报告式的调查问卷由四大部分组成:未治疗期的患者,治疗期的患者,未治疗期患者的性伴侣,以及治疗期患者的性伴侣。对以下6个方面进行评估:自信心、勃起的容易度、对勃起功能的满意度、性快感、对性高潮的满意度以及治疗满意度。TSS量表已经过多国有效性检验和心理学测验,被证明能可靠评价患者及其伴侣对ED治疗的满意度。在最近完成的一项双盲、多中心、平行组、灵活剂量的临床试验中,应用这个新的TSS量表比较了ED患者及其伴侣对伐地那非和安慰剂治疗的满意度。结果发现,伐地那非能显着改善勃起功能以及ED患者和伴侣的自信心、感知到的勃起容易度、性快感、对勃起功能、高潮和药物治疗的满意度。     

Evaluation of an alternative dosing regimen with tadalafil, three times per week, for men with erectile dysfunction： SURE study in Italy

Aim： To examine the preference for two dosing regimens of 20 mg of tadalafil, on demand or three times per week, in men affected with erectile dysfunction （ED） in Italy. Methods： Scheduled Use versus on demand Regimen Evaluation （SURE） is a multicenter, crossover and open-label study, involving 94 urology centers in Italy. Patients aged 18 years or older affected with ED for at least 3 months were enrolled and randomized to 20 mg of tadalafil treatment on demand or three times per week for 5-6 weeks. After a 1-week washout, patients were crossed over to the alternate regimen for 5-6 weeks. A treatment preference question was used to determine the preferred treatment regimen. International Index of Erectile Function （IIEF） and Sexual Encounter Profile （SEP） questionnaire were used as efficacy measures. Results： A total of 1 058 men （mean age 54.8 years）, were randomized to treatment. Overall, 59.1% of patients preferred the on-demand regimen and 41.9% preferred the three times per week dosing. Both regimens were efficacious and well tolerated. Although a statistically higher improvement of the IIEF erectile function （IIEF-EF） domain score and the SEP questionnaire was reported for the three times per week compared to the ondemand treatment regimen, this difference was numerically minimal and lacking in clinical significance. Conclusion： Tadalafil is effective and well tolerated whether used on demand or three times per week. Patients should be given the option to choose the best treatment regimen according to personal needs and preferences.     

The efficacy and safety of flexible-dose vardenafil (levitra) in a broad population of European men

BACKGROUND: In fixed-dose studies, vardenafil 5, 10, and 20mg improves erectile function in men with erectile dysfunction (ED). Here, the efficacy and tolerability of vardenafil when used in a flexible-dose regimen was assessed. METHODS: In this multicenter trial, 323 patients randomly received vardenafil 10mg or placebo. After 4 weeks, patients could switch to 5 or 20mg (or corresponding placebo), or remain on 10mg for an additional 4 weeks; dose-switching was optional for the last 4 weeks. Efficacy variables included the IIEF-EF domain score, GAQ, and percentage of positive responses to SEP2/SEP3 questions. RESULTS: The IIEF-EF domain score significantly improved from a baseline of moderate ED (12.6-13.1) to mild ED in men on vardenafil (21.0-24.2) compared with placebo (13.7-15.6) at weeks 4, 8, 12, and last observation carried forward (LOCF) (p<0.005 vs. placebo). A significantly greater proportion of men receiving vardenafil at weeks 4, 8, 12, and LOCF reported improved erections (80-86% vs. 21-36% for placebo, p<0.005). Successful SEP2 rates increased after vardenafil, reaching 84% at weeks 8 and 12 vs. 49-53% receiving placebo (p<0.005 vs. placebo). Vardenafil improved successful SEP3 rates ranging from 58% to 74% compared to 22-34% for placebo. The most common adverse events, flushing and headache, were generally mild and transient. CONCLUSION: In this flexible dose study, vardenafil was well-tolerated, and produced clinically relevant improvements in erectile function in men with ED.     

长期口服小剂量伐地那非治疗按需服药无效ED的疗效观察

目的:评估持续口服小剂量伐地那非治疗按需服药无效的勃起功能障碍(ED)患者的疗效及停药后效果维持状况.方法:将按需服药无效的39例ED患者改用长期口服小剂量伐地那非治疗3个月,在治疗前后及停药后3个月分别记录患者国际勃起功能指数-5(International index of erectile function-5,IIEF-5)评分及患者性生活日记中插入和保持勃起的成功率,并且记录治疗前后夫妻性满意度.结果:本组患者治疗后主要疗效指标均高于治疗前,且治疗前后指标差异有统计学意义(P<0.01);停药后3个月,主要指标仍高于基线水平,且差异有统计学意义(P<0.05).结论:每天口服小剂量伐地那非对约半数(48.6%)按需服药无效的ED患者,可改善勃起功能,且安全、有效.     

Improvement in erectile function on vardenafil treatment correlates with treatment satisfaction in both patients and their partners

OBJECTIVE: To evaluate the effect of vardenafil on both erectile function (EF) and treatment satisfaction (an aspect of quality of life) in men and their partners, as erectile dysfunction (ED) has a profound effect on patients' quality of life and that of their partners, and treatment for ED tends to be focused on improving functional measures of EF. PATIENTS, SUBJECTS AND METHODS: For this randomized, double-blind, placebo-controlled trial, men with ED for >6 months, according to the USA National Institutes of Health Consensus Statement, were recruited. In all, 611 patients were randomized to treatment with either vardenafil (10 mg for 4 weeks, titrated to preferred dose, 5, 10 or 20 mg, during the next 8 weeks, and maintained at preferred dose for the following 14 weeks), or placebo. RESULTS: At 18 weeks (primary endpoint), the mean improvement in the EF domain of International Index of EF (IIEF-EF) vs baseline was significantly greater with vardenafil than placebo (12.70 vs 1.69, P < 0.001). This was accompanied by significant benefits at 26 weeks and in various secondary variables relating to sexual satisfaction. Qualitative assessment of the treatment effect revealed three categories of importance to patients: effectiveness, confidence and quality of life. There were significant linear correlations between patients' EF and treatment satisfaction, and between patients' EF and their partners' treatment satisfaction. CONCLUSIONS: Functional improvements in response to vardenafil treatment are significantly correlated with treatment satisfaction for both patients with ED and their partners. These findings apply to patients with a wide range of baseline characteristics.     

伐地那非治疗ED的有效性及安全性研究

目的:探讨长期按需服用伐地那非治疗ED的有效性及安全性.方法:2007年3月至2010年1月,共筛选891例ED患者给予口服伐地那非20 mg,每3天1次,通过电话采用问卷调查的方式进行随访,了解ED患者一般资料,治疗的需求、态度、接受程度;服用药物后均要和伴侣性接触,治疗12周后对临床疗效、不良反应、患者以及伴侣满意...     

Chronische PDE-5-Hemmung bei erektiler Dysfunktion

Erectile dysfunction (ED) is often associated with increased cardiovascular risk. There is increasing evidence suggesting that dysfunction of the vascular endothelium with reduced bioavailability of nitric oxide (NO) may be the pathogenetic link between ED and cardiovascular disease. The crucial importance of the NO-guanylatecyclase-cGMP-phosphodiesterase pathway for penile erection is mirrored by the efficacy of phosphodiesterase-5 (PDE5) inhibitors in the treatment of ED. In contrast to other currently available PDE5 inhibitors with a half-life time of about 4 h Tadalafil has a half-life time of about 17.5 h resulting in erectile responsiveness for up to 36 h after 1 single dose. Most clinical experience has been reported with on-demand use of PDE-5 inhibitors, but meanwhile several studies were able to demonstrate that Tadalafil given daily in low (2.5 and 5 mg) doses is both highly effective and well-tolerated. In three randomized, double-blind, placebo-controlled multi-center trials, various validated measures of erectile function indicated that once daily Tadalafil at doses of 2.5, 5, and 10 mg was significantly superior to placebo. In another mono-center trial, once daily Tadalafil has shown significant efficacy even after failure of on-demand treatment. In a controlled cross-over study of on-demand versus daily Tadalafil treatment, 72% of the patients preferred once daily administration, mainly because of superior and longer efficacy allowing a more spontaneous sexual life. Interestingly in a pilot study of on-demand versus chronic administration of Tadalafil for 4 weeks, only regular dosing improved several markers of endothelial function.     

Platelet Cyclic Guanosine Monophosphate as a Biomarker of Phosphodiesterase Type 5 Inhibitor Efficacy in the Treatment of Erectile Dysfunction: A Randomized Placebo-Controlled Study

Background

Phosphodiesterase 5 inhibitors (PDE5-Is) are a mainstay in the therapy of erectile dysfunction (ED). The primary end point of clinical efficacy, both in clinical studies and normal practice, is represented by the International Index of Erectile Function (IIEF).

Objective

To evaluate if platelet cyclic guanosine monophosphate (cGMP) could represent a valuable marker for PDE5-I activity in ED.

Design, setting, and participants

The study enrolled 46 patients with psychogenic, organic, and mixed ED (20–71 yr of age; IIEF score <26). Patients were randomized to 6 wk of vardenafil, 5 mg/d at bedtime, or placebo.

Intervention

All patients donated two blood samples, one before starting the protocol and the second after 6 wk of treatment.

Measurements

Platelet cGMP was measured in both placebo and vardenafil groups. All the patients completed the IIEF-Erectile Function (EF) domain and the sexual encounter profile (SEP) and underwent visual sexual stimulation (VSS) coupled with Rigiscan. All the measurements were performed prior to starting the protocol and after the 6 wk of treatment.

Results and limitations

Platelet cGMP production was significantly (p < 0.05) elevated in patients taking 5 mg vardenafil versus placebo. Vardenafil was not superior to placebo in improving IIEF-EF and SEP scores. Conversely, VSS-Rigiscan revealed a significant amelioration (p < 0.028) in the vardenafil group versus placebo. The changes in platelet cGMP level correlated well with VSS-Rigiscan (p = 0.0037) but not with IIEF-EF and SEP.

Conclusions

Platelet cGMP could represent a relatively simple, reliable, and objective biomarker of PDE5-I activity in ED clinical studies. Larger clinical studies are needed to further validate the use, utility, and limits of this assay.     

The future of erectile dysfunction (ED)

About 30-40 % of ED patients are non-responders to PDE 5 inhibitor monotherapy. Lifestyle modifications and physical activity with weight loss enhance PDE 5 inhibitor responsiveness. The same applies for combination therapies such PDE 5 inhibitors + L-Arginine 3.000mg, PDE 5 inhibitors + statins and PDE 5 inhibitors + Yohimbine. Combination of daily dosing with Tadalafil 5 mg and on demand application of sildenafil or vardenafil can improve responsiveness and erection hardness (personal experiences). Guanylate cyclase activators or RhoA-kinase inhibitors, either as monotherapy or in combination with PDE 5 inhibitors have shown in preclinical settings the potential to improve erectile function and represent targets for new ED drugs in the future. Immunophilin ligands were able to ameliorate erectile function after cavernous nerve injury due to pelvic surgery. Although having shown convincing efficacy both in animals and humans the centrally acting Melanocortin Receptor (MCR) Agonists were given up for ED treatment because of unfavorable side-effects.Promising targets for ED therapy in the future is gene therapy with several targets as well as stem cell therapy with adipose-derived or muscle-derived stem cells.     

Treating erectile dysfunction by endothelial rehabilitation with phosphodiesterase 5 inhibitors

A large body of evidence has accumulated demonstrating that a common pathway in conditions such as hypertension, atherosclerosis, hypercholesterolemia, diabetes mellitus, and erectile dysfunction (ED) is endothelial dysfunction. Although a complete pharmacological cure for ED is currently unavailable, the phosphodiesterase 5 (PDE5) inhibitors sildenafil, vardenafil, and tadalafil are efficacious oral therapy for ED. Results from recent studies suggest that regular treatment with a PDE5 inhibitor may lead to enhanced erectile function (EF) beyond that observed with on-demand usage, possibly through improvement of endothelial function. Such an effect may be viewed as rehabilitation of damaged erectile tissue. The present review focuses on several recent studies which provide evidence for the beneficial effect of regular PDE5 inhibitor administration on the improvement of EF by rehabilitation of vascular endothelium.     

他达那非不同给药方法治疗勃起功能障碍的疗效观察

目的:评估他达那非按需给药和每日给药1次治疗勃起功能障碍(ED)的疗效。方法:随机将ED男性分为按需给药组、每天5 mg他达那非组及每天10 mg他达那非组,治疗周期42 d,应用"性活动日志"来评估疗效,同时监测药物不良反应及重要迹象来评估药物安全性。结果:共53例患者完成研究,3组均对ED有较好的疗效,能显著提高性交成功率,并且药物的不良反应相当,均可以耐受。每日给药1次组SEP的5个问题阳性结果与按需给药组类似。结论:每日给药1次与按需给药在增加患者的勃起次数以及性体验满意度方面没有差异。     

Comparison of the efficacy and safety of once-daily dosing and on-demand use of udenafil for type 2 diabetic patients with erectile dysfunction

We compared the efficacy and safety between once-daily dosing and on-demand use of udenafil for type 2 diabetic patients with erectile dysfunction (ED). A multi-center, randomized, open-label, parallel-group, 12-week study was conducted. 161 patients who improved with on-demand 200 mg of udenafil according to Sexual Encounter Profile (SEP) diary Question 2 and 3 (Q2 and Q3) were randomized into 200 mg on-demand (n = 80) or 50 mg once-daily (n = 81) dosing groups for 8 weeks. The dosing period was followed by a 4-week treatment-free period. The primary efficacy endpoint was the change of the International Index of Erectile Function (IIEF) erectile function domain (EFD) score. The secondary efficacy endpoints included changes to the SEP diary Q2, Q3, IIEF Q3, Q4, other domains of IIEF, Global Assessment Question, and shift to the normal rate (EFD ≥ 26). Vascular endothelial markers were also assessed. The IIEF-EFD score of both groups improved after 8 weeks of treatment (P < 0.0001). There was no statistically significant difference between two groups. Improvement was not maintained after the treatment-free follow-up period. Similar results were observed in the secondary efficacy endpoints. There was also no significant difference in vascular endothelial markers. Daily udenafil was well-tolerated, and there was no significant difference in the adverse drug reactions and adverse events between the two groups. Flushing and headache were the most frequent adverse events. Both regimens improved ED in diabetic patients and were well-tolerated. Further studies are needed to assess the effect of daily udenafil treatment in diabetic patients.     

勃起功能障碍患者及其伴侣偏好他达拉非治疗

5型磷酸二酯酶(phosphodiesterase type 5,PDE5)抑制剂———西地那非、他达拉非和伐地那非是治疗勃起功能障碍(erectile dysfunction,ED)的一线药物。给予患者尝试所有三种药物的机会可以大大提高患者的治疗依从性,同时大多数患者会偏好使用其中一种药物。ED患者普遍偏好使用他达拉非,而且不受ED病情、病因、给药顺序、患者年龄以及剂量的影响。女性伴侣与ED患者的药物选择偏好基本一致,并影响男性伴侣的药物选择。他达拉非起效时间长达36 h,患者可以在较为自由的治疗时间窗内达到勃起,无需刻意安排服药与性活动尝试,性活动时压力明显下降,有助于改善患者的心理状态以及与伴侣的关系。女性伴侣感到回归轻松、自然的性活动,性生活质量得到了整体改善。临床医师开具PDE5抑制剂处方时应考虑患者及其伴侣的药物选择偏好。     

Safety and efficacy of vardenafil in patients with erectile dysfunction: Result of a bridging study in Japan

AIM: Vardenafil is a selective and highly potent phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), with improved selectivity for PDE5 and demonstrated efficacy for improving sexual function in men with ED. The current study investigated the safety and efficacy of this new PDE5 inhibitor in Japanese men with ED. METHODS: This was a prospective, double blind, randomized clinical trial designed to evaluate the efficacy and safety of vardenafil. Following a 4-week treatment-free observation period, 283 eligible patients were randomized to 12 weeks treatment with vardenafil 5 mg, 10 mg, 20 mg, or placebo. Primary efficacy responses were assessed using the scores of Q3 and Q4 of the international index of erectile function (IIEF). RESULTS: All three vardenafil doses showed significantly better improvement than the placebo group in Q3 and Q4 scores of the IIEF questionnaire, either at 12 weeks or at the 'last observation carried forward' (LOCF, P < 0.0001). Q3 scores were improved to 4.06 with vardenafil 5 mg, 4.53 with vardenafil 10 mg, and 4.64 with vardenafil 20 mg, versus 3.17 with placebo. Comparable scores for Q4 were 3.47, 4.15 and 4.31 versus 2.31 for placebo. Up to 86% of patients achieved improved erections as assessed by the global assessment question (GAQ). Reported adverse event rates were 35.3%, 45.3% and 54.5% with vardenafil 5 mg, 10 mg and 20 mg, respectively, versus 21.1% in the placebo group. No serious adverse drug reactions were reported. The most common treatment-emergent adverse events were transient headache, flushing and rhinitis, which were mostly mild. CONCLUSION: Vardenafil is an effective and well-tolerated treatment for ED and provides improvement in key indices of erectile function among Japanese men with ED. The results of our trial show that up to nearly 90% of patients achieve improved erections with the administration of vardenafil.     

Chronic low dosing of phosphodiesterase type 5 inhibitor for erectile dysfunction

Oral phosphodiesterase type 5 (PDE5) inhibitors have provided non-invasive, effective, and well-tolerated treatments for patients with erectile dysfunction (ED). However, many patients with ED are unresponsive to 'on-demand' PDE5 inhibitors. In addition, the lack of spontaneity and naturalness of the on-demand regimen could be a reason for decreased compliance with PDE5 inhibitors. Recently, tadalafil and udenafil were approved for low-dose daily administration for the treatment of ED. Since the introduction of the concept of daily administration of PDE5 inhibitors, several reports have supported the potential benefits of this therapy for disease modification, improvement of the treatment response in difficult-to-treat populations, spontaneity, and safety, although further research is needed to better address these hypotheses. In this article, we reviewed the daily administration of PDE5 inhibitors in terms of pharmacokinetics, safety, efficacy, and distinct features.