Comparison of the clinical efficacy and safety of the on‐demand use of paroxetine,dapoxetine, sildenafil and combined dapoxetine with sildenafil in treatment of patients with premature ejaculation: A randomised placebo‐controlled clinical trial

The aim of the study was to compare the clinical efficacy and safety of the on‐demand use of paroxetine, dapoxetine, sildenafil and combined dapoxetine with sildenafil in treatment of patients with premature ejaculation (PE). In a single‐blind placebo‐controlled clinical study, 150 PE patients without erectile dysfunction (ED) were included during the period of March 2015 to May 2016. Patients were randomly divided into five groups (30 patients each). On demand placebo, paroxetine (30 mg), dapoxetine (30 mg), sildenafil citrate (50 mg) and combined dapoxetine (30 mg) with sildenafil citrate (50 mg) were given for patients for 6 weeks in each group respectively. All patients were instructed to record intravaginal ejaculatory latency time (IELT) and evaluated with Premature Ejaculation Diagnostic Tool (PEDT) and the patient satisfaction score before and after treatment. The mean of IELT, satisfaction score and PEDT in all groups was significantly improved after treatment (p value = .001). Combined dapoxetine with sildenafil group had the best values of IELT, satisfaction scores and PEDT in comparison with other treatment groups (p value <.001). The combined dapoxetine with sildenafil therapy could significantly improve PE patients without ED as compared to paroxetine alone or dapoxetine alone or sildenafil alone with tolerated adverse effects.     

A multicenter, randomized, double-blind, crossover study to evaluate patient preference between tadalafil and sildenafil

PURPOSE: To assess patient preference for erectile dysfunction treatment between either sildenafil or tadalafil, each administered with their respective dosing instructions, and to evaluate preference for either sildenafil or tadalafil dosing instructions during tadalafil therapy. METHODS: We conducted a randomized, double-blind, crossover study consisting of four treatment arms. Because the dosing instructions for sildenafil and tadalafil are different, a unique methodology using sham placebo arms was employed to maintain the blind. To assess drug preference, 219 patients were randomized to either sildenafil 50 mg or tadalafil 20 mg, with dosing instructions reflecting their respective product profiles. To assess dosing instruction preference during tadalafil therapy, 46 patients were randomized to tadalafil 20 mg with either tadalafil or sildenafil dosing instructions. After 12 weeks, patients were crossed-over. After 4 weeks of each treatment, all patients following sildenafil dosing instructions were offered the opportunity for an upward dose titration. In a double-blind fashion, all patients who requested an upward titration received additional capsules. To mimic the pattern of dose usage observed in clinical practice, the number of patients who received additional double-blind active medication was limited to 35% of patients taking sildenafil in each treatment period in each country. Following the crossover treatment period, patients chose their preferred double-blind treatment with dosing instructions to receive in the 12-week extension period. RESULTS: In the drug preference assessment, 132 of 181 (73%) evaluable patients chose to receive tadalafil (p < 0.001) during the extension period. In the dosing instruction preference assessment, 24 of 36 (67%) evaluable patients preferred tadalafil with tadalafil dosing instructions (p = 0.046). Sildenafil and tadalafil were well tolerated. CONCLUSIONS: In the doses utilized in this study, 73% of patients preferred tadalafil with tadalafil dosing instructions for the treatment of their erectile dysfunction over sildenafil with sildenafil dosing instructions. During tadalafil therapy, 67% of patients preferred tadalafil dosing instructions over sildenafil dosing instructions.     

The role of pharmacokinetics and pharmacodynamics in phosphodiesterase-5 inhibitor therapy

Differences in clinical pharmacology of the currently marketed phosphodiesterase (PDE)5 inhibitors sildenafil, vardenafil and tadalafil are largely determined by their pharmacokinetic (PK) properties and their PDE5 inhibitory activity profile. This review outlines the basic concepts of pharmacokinetics and pharmacokinetic pharmacodynamic (PK/PD) relationships and their relevance to dose selection and applied pharmacotherapy. It is followed by a detailed comparative discussion on the pharmacokinetics and exposure-response relationship of the currently available PDE5 inhibitors, including known drug-drug interactions and dosage adjustments in special populations. The review is aimed at providing a critical assessment of the pharmacokinetics of PDE5 inhibitors, which may assist clinicians in tailoring drug and/or treatment regimens to the unique needs of each individual patient with erectile dysfunction.     

Tadalafil vs sildenafil patient preference in Spanish men with erectile dysfunction: results from an International Multicentric Study

ObjectiveTo compare patient preference for sildenafil citrate (sildenafil) vs. tadalafil and for their respective dosing instructions in a cohort of Spanish patients with erectile dysfunction (ED)Material and methodsSixty four Spanish patients from a multicenter, two period, cross-over, double-blind study (265 patients enrolled in total) were randomized to receive on-demand sildenafil 50 mg or tadalafil 20 mg for 12 weeks and afterwards were crossed over to the alternate regimen for another 12 weeks to assess drug preference in an extension period of the study. Similarly, to evaluate preference for their respective dosing instructions, 30 patients were randomized to one of the 2 arms treated with tadalafil: one with sildenafil (S) dosing instructions and the other with tadalafil (T) dosing instructionsResultsSeventy percent of 56 patients completing the study chose to receive tadalafil treatment versus sildenafil treatment (30%) in the extension period (p < 0.01). Correspondingly, 73% of 13 evaluating each drug dosing instructions preferred T dosing instructions (p>0.05). Preference did not vary with age, concomitant diseases and previous use of sildenafilConclusionsIn this study, 7 out of 10 patients preferred tadalafil and its dosing instructions to sildenafil, for the treatment of their ED     

An open-label, multicentre, randomized, crossover study comparing sildenafil citrate and tadalafil for treating erectile dysfunction in men naïve to phosphodiesterase 5 inhibitor therapy

Associate Editor Michael G. Wylie Editorial Board Ian Eardley, UK Jean Fourcroy, USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar, UK Alvaro Morales, Canada Michael Perelman, USA Marcel Waldinger, Netherlands

OBJECTIVES

To compare treatment preference, efficacy, and tolerability of sildenafil citrate (sildenafil) and tadalafil for treating erectile dysfunction (ED) in men naïve to phosphodiesterase 5 (PDE5) inhibitor therapy.

PATIENTS AND METHODS

This was an open‐label, crossover study of sildenafil and tadalafil (taken as needed). After a 4‐week baseline assessment, 367 men with ED (mean age 54 years) were randomized to receive sildenafil for 12 weeks followed by tadalafil for 12 weeks or vice versa (8‐week dose optimization and 4‐week assessment phases). During dose optimization, patients started taking 25‐ or 50‐mg sildenafil or 10‐mg tadalafil and could titrate to find their optimum dose (25‐, 50‐ or 100‐mg sildenafil; 10‐ or 20‐mg tadalafil). After completing both 12‐week periods, patients chose which treatment to continue during an 8‐week extension. Efficacy was measured with the International Index of Erectile Function (IIEF) and Sexual Encounter Profile (SEP) diary.

RESULTS

Of the 291 men who completed both treatments, 85 (29%) chose sildenafil and 206 (71%) chose tadalafil (P < 0.001) for the 8‐week extension. The IIEF erectile function domain scores were 14.2 at baseline, 23.9 at endpoint on sildenafil, and 24.3 at endpoint on tadalafil (P = 0.08, sildenafil vs tadalafil). The mean per patient percentage success scores for SEP2 (penetration) were: baseline (46%), sildenafil (post‐baseline 82%) and tadalafil (post‐baseline 85%; P = 0.06, sildenafil vs tadalafil), and for SEP3 (successful intercourse) were: baseline (19%), sildenafil (post‐baseline 72%), and tadalafil (post‐baseline 77%; P = 0.003, sildenafil vs tadalafil). The only treatment‐emergent adverse events that were reported by >5% of men were headache and flushing.

CONCLUSIONS

In men with ED who were naïve to PDE5 inhibitor therapy, sildenafil and tadalafil were both effective and well tolerated. After treatment with sildenafil and tadalafil, 29% of men chose sildenafil and 71% chose tadalafil for ED therapy during an 8‐week extension.

     

A Novel Treatment of Premature Ejaculation

The investigation of the etiology and treatment of premature ejaculation (PE), a common and significant problem for men and their partners, has been limited by the lack of defined outcomes and differences in clinical trial designs. Currently, no medication has been approved for the treatment for PE worldwide. Recognition of serotonin as a key mediator in ejaculatory signaling has raised interest in the utility of pharmacologic intervention for treating PE. Selective serotonin reuptake inhibitors (SSRIs) have been used off-label for PE, with varied results. However, treatment with currently available SSRIs typically requires chronic dosing that increases drug accumulation and the attendant risk of adverse events. Dapoxetine is an SSRI with a short half-life (1.2 h), developed specifically for the treatment of men with PE. This agent has a unique pharmacokinetic profile characterized by rapid absorption and elimination. Dapoxetine is metabolized by multiple pathways, and no clinically relevant drug–drug interactions have been identified. Furthermore, dapoxetine pharmacokinetics do not appear to be affected by food, age, alcohol, or phosphodiesterase type 5 (PDE5) inhibitors to a relevant degree. In two placebo-controlled phase 3 trials involving >2600 men with PE, dapoxetine 60 mg given as needed over 12 wk significantly prolonged the stopwatch-assessed intravaginal ejaculatory latency time (IELT) from 0.91 min at baseline to 3.32 min (p < 0.0001), increased control over ejaculation, and increased sexual satisfaction for men and their partners compared with placebo (both p < 0.0001). These results suggest that dapoxetine may meet the medical need for on-demand therapy for PE.     

Evidence for contamination of herbal erectile dysfunction products with phosphodiesterase type 5 inhibitors

PURPOSE: We determined if pharmacological dosages of phosphodiesterase type 5 inhibitors (PDE5) inhibitors were present within a group of natural products marketed for the treatment of erectile dysfunction. MATERIALS AND METHODS: Seven herbal products marketed for the treatment of erectile dysfunction were purchased via the Internet or at local health food stores. Specimens were batched, relabeled and blindly analyzed for contamination with PDE5 inhibitors. High performance liquid chromatography and mass spectrometry were used to detect evidence of contamination with sildenafil, tadalafil or vardenafil. RESULTS: Of the 7 tested products 2 contained pharmacological dosages of sildenafil and tadalafil. Contamination with vardenafil was not identified. Mean dosages of sildenafil and tadalafil were 30.2 and 19.7 mg, respectively. CONCLUSIONS: A significant proportion of natural products marketed for erectile dysfunction contains PDE5 inhibitors. Although marketed as natural products devoid of adverse effects, these agents are known to have potentially fatal drug interactions with nitrates. Better regulation of the natural health products industry is urged.     

The treatment of erectile dysfunction study: focus on treatment satisfaction of patients and partners

OBJECTIVE: To assess patient and partner preferences for, and satisfaction with, tadalafil or sildenafil (phosphodiesterase type 5 inhibitors) in routine clinical practice for treating erectile dysfunction (ED), as these are important outcomes that might influence treatment adherence. PATIENTS AND METHODS: In a multicentre, prospective observational trial in Canada, patients with ED were eligible if they planned to change treatment from tadalafil to sildenafil or vice versa. Data were collected at baseline and 4-12 weeks later (endpoint). Satisfaction was assessed using patient and partner versions of the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire. EDITS index scores range from 0 (extremely low treatment satisfaction) to 100 (extremely high treatment satisfaction). RESULTS: Of 2425 patients, approximately 98% completed the study and 295 partners participated. When patients changed from sildenafil to tadalafil (1722 men) the mean EDITS index scores increased significantly for both patients (from 61.6 to 78.3) and partners (from 65.0 to 82.6; both P < 0.001). When patients changed from tadalafil to sildenafil (703 men), the mean EDITS index scores increased slightly but significantly for patients (from 68.8 to 70.2; P = 0.007) but not partners (from 76.8 to 68.9; P = 0.066). For the individual EDITS questions, mean scores increased significantly from baseline to endpoint on all questions for patients (all 11 questions; P < 0.001) and partners (all five questions; P < 0.001) in the sildenafil-to-tadalafil group, and in the tadalafil-to-sildenafil group, mean scores for patients decreased on nine of 11 questions (seven of nine significantly; P < 0.041) and mean scores for partners decreased on all five (two significantly; P < 0.049). For treatment preference, regardless of the change in treatment (i.e. sildenafil-tadalafil or tadalafil-sildenafil), a significantly higher percentage of patients and partners preferred tadalafil to sildenafil. CONCLUSIONS: These data indicate that patients with ED (and their partners) who changed from sildenafil to tadalafil treatment or vice versa in a routine clinical practice setting had higher treatment satisfaction when taking tadalafil than sildenafil, as assessed by most measures of EDITS. The higher treatment satisfaction with tadalafil might help to explain the greater preference for tadalafil compared with sildenafil in both patients and partners in this observational study.     

Factors associated with preference for sildenafil citrate and tadalafil for treating erectile dysfunction in men naïve to phosphodiesterase 5 inhibitor therapy: post hoc analysis of data from a multicentre, randomized, open-label, crossover study

OBJECTIVES: To determine if baseline characteristics, treatment efficacy, psychosocial outcomes or tolerability were associated with patient preference for sildenafil citrate (sildenafil) or tadalafil for treating erectile dysfunction (ED) in men naive to phosphodiesterase 5 inhibitor therapy. PATIENTS AND METHODS: In an open-label, crossover study of sildenafil (25, 50 or 100 mg) and tadalafil (10 or 20 mg), dosed as needed, after a 4-week baseline assessment, 367 men with ED were randomly assigned to sildenafil followed by tadalafil or vice versa (8-week dose optimization and 4-week assessment phase for each treatment period). Patients completing both periods chose which treatment they preferred for an 8-week extension phase. Bivariate logistic regression and stepwise logistic regression were used to determine if any baseline characteristics or post-baseline measurements were associated with the patients' treatment preference. Baseline variables examined were age, race, ED aetiology/duration, body mass index, smoking status, alcohol consumption, vital signs, comorbid medical conditions, and baseline scores for the International Index of Erectile Function (IIEF) domains, Psychological and Interpersonal Relationship Scales (PAIRS) domains, and Sexual Encounter Profile (SEP) diary questions. Post-baseline variables examined were therapy sequence, dosage, and differences in IIEF and PAIRS domains, SEP scores, in number/timing of sexual attempts and in the severity of side-effects (overall patient perception). RESULTS: Of 291 patients completing both treatments and indicating a preference, 85 (29%) preferred sildenafil and 206 (71%) preferred tadalafil. Variables were individually analysed using bivariate analysis; one baseline characteristic (presence/absence of hyperlipidaemia) and 13 post-baseline measurements were significantly associated with the patients' treatment preference. Variables were analysed as a group using stepwise logistic regression; a set of six post-baseline factors was identified as significantly associated with patient preference. Dosage choice, reductions in the PAIRS time concerns domain, IIEF intercourse satisfaction domain improvements, smaller side-effect severity scores, more sexual attempts, and increased SEP4 scores (satisfaction with erection hardness) during the tadalafil or sildenafil treatment periods were all significantly associated with preference for tadalafil or sildenafil. CONCLUSIONS: We identified no baseline characteristics that prospectively distinguish patients who will prefer tadalafil or sildenafil. Patient differences in time concerns, dosage choice, intercourse satisfaction, treatment tolerability, number of sexual attempts and satisfaction with erection hardness were the set of factors most significantly associated with treatment preference, and the preference observed for tadalafil (71%) or sildenafil (29%) might be substantially accounted for by differences in these factors during the tadalafil and sildenafil treatment periods.     

Time/duration effectiveness of sildenafil versus tadalafil in the treatment of erectile dysfunction in male spinal cord-injured patients

STUDY DESIGN: A randomized, blinded, crossover clinical trial comparing sildenafil versus tadalafil for erectile dysfunction (ED) in male spinal cord-injured (SCI) patients. OBJECTIVES: To compare the safety, time/duration effectiveness, and the impact on the quality of life (QoL) of tadalafil 10 mg versus sildenafil 50 mg. SETTING: Neurourology Section, Careggi Hospital, Florence, Italy. METHODS: During a screening (visit 1), a diary card was distributed, in which the subjects assessed, after each attempt at intercourse the quality of their erection, responding (Yes/No) to both Sexual Encounter Profile Questions 2 (SEP2) and 3 (SEP3). The subjects made at least four attempts at intercourse. At visit 2, 15 patients (group 1) were assigned sildenafil and 15 (group 2) started with tadalafil. Responses to baseline International Index of Erectile Function 5 items (IIEF-5), Questions 13-14 (IIEF 15 items) and SEP diary were recorded. Patients attempted intercourse on four separate occasions: within 4 h of taking the first tablet, within 12 h for the second tablet, 24 h for the third, and the fourth from 24 to 36 h. At visit 3, the investigators evaluated the effectiveness with the same measures used at baseline. After a wash-out period, at visit 4, Group 1 was given tadalafil, and Group 2 was given sildenafil. Patients were required to observe the same criteria in taking the four tablets as in visit 2. After 4 weeks (visit 5), we evaluated the patients as we did in visit 3. RESULTS: Overall, 28 patients completed the study. No subjects discontinued the drugs due to drawbacks.Tadalafil allowed a majority of men in this trial to achieve both normal sexual functioning up to 24 h postdosing compared to sildenafil (P<0.01) and improved overall sex life satisfaction as well as sexual relations with partner. CONCLUSION: Based on these data, tadalafil may have the potential to become an important treatment option for ED in SCI patients. SPONSORSHIP: This study was not sponsored.     

帕罗西汀与达帕西汀的对比，治疗早泄的新的选择性5-羟色胺再摄取抑制剂

达帕西汀氢氯化物是一种选择性5-羟色胺再摄取抑制剂,也是第一种被批准可以按需服用治疗早泄的药物。本文目的为研究按需服用达帕西汀（30mg和H60mg）和每日服用帕罗西汀（20mg）对早泄的疗效。研究募集了150名患者进行了长达1个月的研究。患者被分成3组,每组50人。第一组按需服用达帕西汀30mg。第二组按需服用达帕西汀60mg。第三组每日服用帕罗西汀20mg。治疗结束后,我们的结果检测值相对于基准阴道内射精潜伏期（IELT）延长了。与基准IELT相比,帕罗西汀组、30mg达帕西汀组和60mg达帕西汀组的治疗后IELT分别延长了117％（P〈0．01）,117％（P〈0．01）和170％（P〈0．01）。30mg达帕西汀组和帕罗西汀组的IELT增幅相同（P〉0．05）,而60mg达帕西汀组的IELT增幅明显高于30mg达帕西汀组（P〈0．05和帕罗西汀组P〈0．01）。性交前1～3小时服用达帕西汀60mg是针对早泄的非常有效的治疗方法。然而,与当前普遍使用的帕罗西汀相比,达帕西汀30mg疗效并不显著。     

Effects of sildenafil citrate (Viagra) on hemodynamic parameters during exercise testing and occurrence of ventricular arrhythmias in patients with erectile dysfunction and cardiovascular disease

BACKGROUND: Erectile dysfunction (ED) is frequently observed in male cardiovascular disease (CVD) patients, creating concern about cardiac risk of their sexual activity, and their therapeutic use of sildenafil. Relatively little information exists about sildenafil effects on exercise testing, hemodynamic parameters or on occurrence of ventricular arrhythmias during normal activities in CVD patients. HYPOTHESIS: Single, oral doses of sildenafil do not significantly affect exercise-induced changes in hemodynamic parameters or occurrence of arrhythmias in ED/CVD patients. METHODS: ED patients, with or without CVD, were enrolled in one of two studies. In the first, patients underwent standard (Bruce Protocol) treadmill tests; an initial control test was followed 1 hour later by administration of 100mg oral sildenafil. After another hour, they underwent a second treadmill test. Systolic and diastolic blood pressure (SBP and DBP), heart rate, and double product were determined for each evaluation at pretest, maximum stress, and recovery. In the second, Holter ambulatory ECGs were recorded 5 hours before and 6 hours after 100mg oral sildenafil administration. RESULTS: Sildenafil had no clinically significant effects on exercise-induced changes in hemodynamic parameters in cardiac patients and only slight, clinically insignificant effects in noncardiac patients. ECG showed sildenafil did not affect incidence of ventricular arrhythmias. CONCLUSIONS: Sildenafil does not alter hemodynamic response to exercise or change incidence of ventricular arrhythmias in men with CVD and ED. These results suggest that, when used in accordance with prescribing information and current treatment guidelines, sildenafil should be safe for most patients with both these conditions.     

An open-label,multicenter, randomized,crossover study comparing sildenafil citrate and tadalafil for treating erectile dysfunction in Chinese men na?ve to phosphodiesterase 5 inhibitor therapy

The study was to compare treatment preference, efficacy, and tolerability of sildenafil citrate (sildenafil) and tadalafil for treating erectile dysfunction (ED) in Chinese men naïve to phosphodiesterase 5 (PDE5) inhibitor therapies. This multicenter, randomized, open-label, crossover study evaluated whether Chinese men with ED preferred 20-mg tadalafil or 100-mg sildenafil. After a 4 weeks baseline assessment, 383 eligible patients were randomized to sequential 20-mg tadalafil per 100-mg sildenafil or vice versa for 8 weeks respectively and then chose which treatment they preferred to take during the 8 weeks extension. Primary efficacy was measured by Question 1 of the PDE5 Inhibitor Treatment Preference Questionnaire (PITPQ). Secondary efficacy was analyzed by PITPQ Question 2, the International Index of Erectile Function (IIEF) erectile function (EF) domain, sexual encounter profile (SEP) Questions 2 and 3, and the Drug Attributes Questionnaire. Three hundred and fifty men (91%) completed the randomized treatment phase. Two hundred and forty-two per 350 (69.1%) patients preferred 20-mg tadalafil, and 108/350 (30.9%) preferred 100-mg sildenafil (P < 0.001) as their treatment in the 8 weeks extension. Ninety-two per 242 (38%) patients strongly preferred tadalafil and 37/108 (34.3%) strongly the preferred sildenafil. The SEP2 (penetration), SEP3 (successful intercourse), and IIEF-EF domain scores were improved in both tadalafil and sildenafil treatment groups. For patients who preferred tadalafil, getting an erection long after taking the medication was the most reported reason for tadalafil preference. The only treatment-emergent adverse event reported by > 2% of men was headache. After tadalafil and sildenafil treatments, more Chinese men with ED naïve to PDE5 inhibitor preferred tadalafil. Both sildenafil and tadalafil treatments were effective and safe.     

Time from dosing to sexual intercourse attempts in men taking tadalafil in clinical trials

OBJECTIVE: To determine whether patients with erectile dysfunction (ED) and treated with tadalafil use the 36-h duration of effect of the drug, and to discern if the timing of intercourse attempts is influenced by patient age, baseline severity of ED, or previous experience with sildenafil citrate. PATIENTS AND METHODS: In 11 multicentre, double-blind, placebo-controlled studies, 2102 patients with ED were randomized to a maximum of one dose per day of tadalafil 10 or 20 mg (1464 men), or placebo (638 men) with no time restrictions before attempting sexual activity after the dose. A post hoc analysis was used to determine the proportion of men with ED who attempted sexual intercourse during various intervals (>0 to < or = 1, >1 to < or = 4, and >4 to < or = 36, including >12 to < or = 36 h) after dosing with tadalafil or placebo over a 12-week period. Patients were stratified by age, baseline severity of ED, and previous history of sildenafil use. RESULTS: Of patients in different age groups and various ED severity, > or = 79% and > or = 53% chose to attempt sexual intercourse at least once during the 12-week treatment period at 4-36 and 12-36 h, respectively, after taking tadalafil. Regardless of previous experience with sildenafil, about a third of patients using tadalafil attempted intercourse a mean of at least once per week at 4-36 h after the dose over 12 weeks. Furthermore, 58% of patients attempted intercourse at least once during two intervals (>1 to < or = 4 h and >12 to < or = 36 h) after separate doses of tadalafil. CONCLUSION: Regardless of age, ED severity, or previous experience with sildenafil, most patients attempted sexual intercourse at least once at 12-36 h after one dose of tadalafil over a 12-week treatment period. Furthermore, by engaging in sexual intercourse at both earlier and later intervals after separate doses, most patients on treatment did not adhere to a fixed schedule of intimacy and thus took advantage of the 36-h duration.     

Therapeutic effectiveness and patient satisfaction after 6 months of treatment with tadalafil, sildenafil, and vardenafil: results from the erectile dysfunction observational study (EDOS)

OBJECTIVE: This observational study was conducted across Europe to assess health outcomes in men with erectile dysfunction (ED) who took tadalafil, sildenafil citrate (sildenafil), or vardenafil HCl (vardenafil) for 6 mo. METHODS: Therapy effectiveness and patient satisfaction were evaluated using established and new questions on erectile function. Behavioural, psychological, and relationship outcomes were assessed using the short form of the Psychological and Interpersonal Relationship Scales (SF-PAIRS). RESULTS: In nine European countries at 904 sites, 8047 patients were enrolled and 94% (7560) selected either tadalafil (5315), sildenafil (1252), or vardenafil (993) for treatment at baseline. Of the 7560, 3998 (52.9%) took the same drug for 6 mo. Baseline characteristics across the three treatment groups were comparable: mean age approximately 56 yr, moderate or severe ED, and mean International Index of Erectile Function-Erectile Function domain score about 13. Tadalafil, sildenafil, and vardenafil were therapeutically effective and improved patient satisfaction in the 40-58% of men who completed 6 mo of a single therapy. Patients taking tadalafil consistently had numerically higher levels of therapeutic effectiveness and satisfaction compared with patients who took sildenafil or vardenafil. The three cohorts had statistically significant changes from baseline in response to SF-PAIRS and there were significant differences, in favour of tadalafil, among cohorts in the Time Concerns domain. CONCLUSION: In a large observational study that mimics a routine clinical setting, most patients selected an inhibitor of phosphodiesterase 5 to treat ED, which resulted in a high level of therapeutic effectiveness and patient satisfaction.     

Treatment preferences in men with erectile dysfunction： an open label study in Korean men switching from sildenafil citrate to tadalafil

To evaluate patient preferences for sildenafil citrate or tadalafil （PDE-5 inhibitors available for the treatment of erectile dysfunction [ED]） and assess potential reasons for these preferences. Methods： This open-label study was conducted on Korean men taking sildenafil, at least 6 weeks prior to study entry, for ED. Following screening, patients continued sildenafil treatment for 4 weeks, then after a 1-week washout period, switched to tadalafil for 8 weeks. Patients then continued with their treatment of choice during an extension phase. Psychosocial factors （time concern, spontaneity, sexual self-confidence） were evaluated using Psychological and Interpersonal Relation- ship Scales （PAIRS）, while timing of dose to sexual attempt patterns were assessed from patient diaries. Results： The present study enrolled 160 Korean men （mean age 55 years） with prior median sildenafil use of 585 days. During the extension phase, 73.7% of patients elected to take tadalafil, whereas 26.3% chose sildenafil （P 〈 0.001）. After switching from sildenafil to tadalafil, mean PAIRS time concern scores decreased from 2.54 to 2.42 （P = 0.002）, with no statistically significant differences observed between the sildenafil and tadalafil assessment phases in sexual spontaneity and self-confidence scores. Sexual attempts made 〉 4 h to 〈 36 h post-dose occurred in 4.5% of patients during the sildenafil assessment phase compared with 17.5% during the tadalafil assessment phase. Conclusion： After experiencing both sildenafil and tadalafil, the majority of patients exhibited a preference for tadalafil. This preference might be influenced by psychosocial factors, such as decreased time concerns, and a broader window of opportunity available for sexual activity.     

Physician-rated patient preference and patient- and partner-rated preference for tadalafil or sildenafil citrate: results from the Canadian 'Treatment of Erectile Dysfunction' observational study

OBJECTIVE: To determine physician-based ratings of patient preference, patient preference, partner preference and physician-based assessment of the reasons for patient preference for tadalafil or sildenafil citrate (sildenafil) as a treatment for erectile dysfunction (ED) in routine clinical practice. Phosphodiesterase type 5 inhibitors (PDE5i) are effective and well-tolerated therapies for ED, but patient and partner preferences for these treatments might be determined by many factors, both medical and nonmedical. PATIENTS AND METHODS: The Treatment of ED (TED) observational trial was a multicentre study conducted in Canada to determine patient and partner preferences for the PDE5i tadalafil or sildenafil in routine clinical practice. Patients who planned to change treatment from tadalafil or sildenafil to the alternative drug were invited to participate in the study. The study duration was 4-12 weeks. At visit 1 (baseline), patient background information was collected. At visit 2, physicians answered the physician-rated patient-treatment preference questionnaire, patients answered the treatment preference question (TPQ) and the global assessment question (GAQ), and partners answered the partner TPQ. RESULTS: The TED study was conducted at 266 sites across Canada and involved 2425 patients who used the allowed study medications, and 295 sexual partners who attended clinic visits. More than 98% of patients completed the study. Responses to the preference questionnaires showed that physician-rated patient preference, patient preference, and partner preference had a similar pattern preference, with a significantly higher proportion preferring tadalafil over sildenafil regardless of the change in treatment (i.e. sildenafil to tadalafil or tadalafil to sildenafil). Responses to the GAQ showed that nearly 90% of the patients who took either PDE5i said that the treatment had improved erections. CONCLUSIONS: TED is the first study to assess physician-based ratings of patient preference, patient preference, and partner preference for tadalafil or sildenafil in a routine clinical practice settings. Most participants preferred tadalafil over sildenafil. Understanding the underlying reasons influencing the preference might improve patient compliance and satisfaction with treatment.     

A three-part study to investigate the incidence and potential etiologies of tadalafil-associated back pain or myalgia

The potential mechanisms underlying back pain and/or myalgia experienced by men taking tadalafil were investigated. An integrated analysis of 10 placebo-controlled tadalafil clinical trials (N=1846) showed that the incidence of back pain and/or myalgia was 9.4% in patients receiving tadalafil 10 mg (N=394), 8.3% in patients receiving tadalafil 20 mg (N=883) and 3.7% in placebo-treated patients (N=569). One (0.3%) patient receiving tadalafil 10 mg, six (0.7%) patients receiving tadalafil 20 mg, and no patients receiving placebo discontinued treatment due to back pain and/or myalgia. In a prospective study in healthy volunteers, no substantial changes were observed in laboratory markers indicative of inflammation or muscle damage, and tadalafil did not affect renal plasma flow nor produce lumbar or gluteal myositis by positron emission tomography scan or magnetic resonance imaging. Although the mechanism of back pain and/or myalgia remains unknown, these events appear to be self-limiting and a general effect of phosphodiesterase 5 inhibition.     

Coadministration of neoral and the novel rapamycin analog, SDZ RAD, to rat lung allograft recipients: potentiation of immunosuppressive efficacy and improvement of tolerability of staggered versus simultaneous treatment

BACKGROUND: Neoral and rapamycin derivative (RAD) have complementary mechanisms for inhibition of lymphocyte activation and are substrates for the same pathways of drug metabolism. Therefore, we investigated treatment regimens designed to minimize pharmacokinetic interactions and to potentiate immunosuppressive efficacy in a highly stringent rat lung allograft model. METHODS: Lewis recipients of Brown Norway lungs received the following daily oral doses: (A) RAD at 2.5 mg/kg (n=9); (B) Neoral at 7.5 mg/kg (n=8); (C) RAD at 2.5 mg/kg + Neoral at 7.5 mg/kg simultaneously (n=8); or (D) RAD at 2.5 mg/kg + Neoral at 7.5 mg/kg (n=6) staggered 6 hr apart. Rats were assessed by daily weights, chest radiographs, drug trough levels (high-performance liquid chromatography/mass spectrometry), and blinded scoring of graft histology at death (day 21). RESULTS: Radiographs were completely opacified in all grafts of control and RAD monotherapy groups on days 7 and 14, respectively. Grafts were mildly opacified (Neoral monotherapy) and completely clear (both RAD + Neoral groups) on day 21. Simultaneous or staggered combined treatment dramatically reduced histologic rejection compared with treatment with either drug alone. Simultaneous treatment caused poor tolerability (poor grooming, lethargy) and significantly higher day-14 RAD and cyclosporine (CsA) trough levels (49+/-5 and 638+/-106 ng/ml; P<0.04) than in the staggered group (28+/-3 and 318+/-25 ng/ml) in which all animals were clinically normal. RAD and CsA day-14 trough levels in the staggered group were the same or lower than trough levels in animals treated with either drug alone (RAD 27+/-3/Neoral 815+/-67 ng/ml). CONCLUSIONS: (1) Administration of RAD + Neoral suppressed lung rejection more effectively than treatment with either drug alone. (2) Trough levels did not differ between monotherapy and staggered combination therapy for RAD but were lower for CsA. These results suggested that pharmacological, rather than pharmacokinetic, interactions between the parent drugs were responsible for the potentiation of immunosuppression when these drugs were coadministered. 3) Staggered administration of RAD+Neoral avoided the pharmacokinetic interactions that caused the elevated drug blood levels and poor tolerability caused by simultaneous administration. Thus, we could potentiate efficacy and improve tolerability by staggering administration of RAD and Neoral.