vardenafil-dihydrochloride and Erectile-Dysfunction

Nowadays, Oral phosphodiesterase type 5 inhibitors (PDE5Is) are widely used for the treatment of erectile dysfunction (ED). However, these drugs have become abused among some men for recreational use to enhance their sexual performance.. To shed a light on the recreational use of oral PDE5Is.. A literature review was performed in the PubMed, Medline Medical Subject Heading, Science Direct, Scopus, Cochrane Library, EMBASE, CINAHL, Academic Search Complete, Google scholar, Egyptian Knowledge Bank (EKB) databases, Medline, Embase, and Chem ID using the keywords; sexual health, erectile dysfunction, recreational use/abuse, phosphodiesterase type 5 inhibitors, sildenafil, tadalafil, vardenafil, avanafil, and adverse effects.. Overall, 52 studies were retained for review out of 166 papers. Twenty-two studies that assessed the prevalence of the problem were investigated including 25,279 men from different countries. Most of these studies were cross-sectional studies that depend on multiple questionnaires representing the extent as well as the attitude of the recreational use of PDE5Is.. Oral PDE5Is have become used among some men for recreational use to enhance their sexual performance. To counteract the possible side effects of such abuse, the media, as well as health authorities, should be aware of the potential adverse effects of such abuse and strengthen the regulatory activity to protect the customers from such risks. Mostafa T, Alghobary MF. Recreational Use of Oral PDE5 Inhibitors: The Other Side of Midnight. Sex Med Rev 2022;10:385-395.

Topics: Erectile Dysfunction; Humans; Male; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Tadalafil; Vardenafil Dihydrochloride

Lodenafil is a class of drugs called an inhibitor of PDE5 which also include a wide range of other erectile medicines, such as sildenafil, tadalafil and vardenafil. It is part of a new generation of PDE5 inhibitors that includes udenafil and avanafil. Lodenafil is a prodrug manufactured in the form of lodenafil carbonate, the carbonate dimer that divides in the body into two active drug lodenafil molecules. The oral bioavailability of this formulation is higher than that of the parent drug. This article discusses, by a critical comprehensive review of the literature on lodenafil in terms of its description, names, formulae, elemental composition, appearance, and therapeutic uses. The article also discusses the methods for preparation of lodenafil, its physical-chemical properties, analytical methods for its determination, pharmacological-toxicological properties, and dosing information.

Topics: Erectile Dysfunction; Humans; Male; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Tadalafil; Vardenafil Dihydrochloride

Erectile dysfunction (ED) is a substantial cause of dissatisfaction among many men. This discontentment has led to the emergence of various drug treatment options for this problem.. Unfortunately, due to various interactions, contraindications, and side effects, systemic therapies such as phosphodiesterase-5 inhibitors (including sildenafil, tadalafil, vardenafil, avanafil, etc.) are not welcomed in many patients. These problems have led researchers to look for other ways to reduce these complications.. This article holistically reviews the efficacy of topical prostaglandins and their role in treating ED. We sought to provide a comprehensive overview of recent findings on the current topic by using the extensive literature search to identify the latest scientific reports on the topic.. In this regard, topical and transdermal treatments can be suitable alternatives. In diverse studies, prostaglandins, remarkably PGE1 (also known as alprostadil), have been suggested to be an acceptable candidate for topical treatment.. Numerous formulations of PGE1 have been used to treat patients so far. Still, in general, with the evolution of classical formulation methods toward modern techniques (such as using nanocarriers and skin permeability enhancers), the probability of treatment success also increases. Hamzehnejadi M, Tavakoli MR, Homayoun F et al. Prostaglandins as a Topical Therapy for Erectile Dysfunction: A Comprehensive Review. Sex Med Rev 2022;10:764-781.

Topics: Alprostadil; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Male; Prostaglandins; Sildenafil Citrate; Tadalafil; Vardenafil Dihydrochloride

Phosphodiesterase 5 inhibitors (PDE5I) represent the first-line treatment in the management of post-operative erectile dysfunction (ED) after pelvic oncological surgery. The aim of our study is to evaluate the available evidence on the efficacy of PDE5Is, including new formulations and penile rehabilitation post-pelvic surgery.. A systematic review of the literature was performed until May 2020. The following databases were searched: Scopus, Medline and Web of Science. The MeSH search was conducted by combining the following terms: 'erectile dysfunction', 'radical prostatectomy' 'pelvic' 'bladder' 'phosphodiesterase' inhibitors' 'avanafil' 'sildenafil' 'tadalafil' 'lodenafil' 'mirodenafil' 'udenafil' 'vardenafil' 'sublingual' 'orodispersible' 'penile' 'rehabilitation'.. Sildenafil, Tadalafil, vardenafil and Avanafil improve EF compared with placebo in men with all levels of ED severity after radical prostatectomy with good tolerability. No specific recommendations can be suggested regarding the superiority of a drug over the other. The optimal dose, continuous vs. on-demand and duration of treatment, is still under investigation. In vitro and preclinical studies suggest the possible role for lodenafil, mirodenafil and oro-dispersible formulations in patients undergoing oncological pelvic surgery. Few studies demonstrated the efficacy of udenafil in improving ED after rectal surgery or radical prostatectomy. Complete recovery of EF after surgery is still an unmet need in the field of penile rehabilitation after pelvic surgery.. PDE5Is have a crucial role in the management of post pelvic surgery of ED. New drugs and new formulations have shown excellent results in patients with ED; however, data in patients after surgery is still scarce. Further well designed RCT should clarify the role of these new compounds and oro-dispersible formulations in the management of ED in patients undergoing pelvic surgery.

Topics: Erectile Dysfunction; Humans; Male; Phosphodiesterase 5 Inhibitors; Prostatectomy; Sildenafil Citrate; Tadalafil; Vardenafil Dihydrochloride

We carried out this systemic review and meta-analysis of relevant randomized controlled trials to determine different dosage regimens of vardenafil in the treatment of male erectile dysfunction (ED).. Using appropriate keywords, we searched PubMed, the Cochrane Library, and Embase for relevant literature before March 2020. We evaluated odds ratio (OR), weighted mean difference (WMD), and 95% confidence interval (95% CI) to assess the results of each study.. We included 14 studies with a total of 3221 patients. Compared with the placebo, vardenafil significantly increased International Erectile Function Index (IIEF) overall satisfaction (WMD 3.37, 95% CI 2.02-4.71), IIEF-erectile function (WMD 7.93, 95% CI 6.00-9.85), IIEF sexual desire (WMD 0.79, 95% CI 0.24-1.35), IIEF intercourse satisfaction (WMD 5.24, 95% CI 3.35-7.13), IIEF orgasmic function (WMD 3.81, 95% CI 2.26-5.35), Sexual Encounter Profile (SEP) Q2 (WMD 26.36, 95% CI 22.95-29.77), and SEP Q3 (WMD 35.18, 95% CI 31.89-38.48).. Vardenafil demonstrated significant efficacy in the treatment of ED, but the optimal dose and course of vardenafil remain to be established.

Topics: Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) is a relatively frequent disease that negatively impacts the overall quality of life, well-being, and relationships. Although the use of phosphodiesterase 5 inhibitors (PDE5is) has revolutionized the treatment of ED, a high percentage of ED patients discontinue PDE5i treatment.. (i) To analyze the reasons for patient dissatisfaction leading to PDE5i discontinuation; (ii) analyze the pharmacokinetics of new formulations focusing on the time needed to reach an effective plasma concentration of PDE5is (T. An online PubMed literature search was conducted to identify English language publications from inception to January 2019.. The main reasons for patient dissatisfaction when using PDE5is on demand are the relatively long T. We conclude that several ODT and ODF formulations can improve the 'discretion' issue because they are taken without water, but they have similar pharmacokinetics to corresponding film-coated tablet formulations. One ODF formulation of sildenafil was characterized by a shorter T

Topics: Administration, Mucosal; Adult; Aged; Aged, 80 and over; Erectile Dysfunction; Humans; Male; Middle Aged; Mouth Mucosa; Patient Compliance; Patient Satisfaction; Phosphodiesterase 5 Inhibitors; Quality of Life; Sexual Behavior; Sildenafil Citrate; Tadalafil; Vardenafil Dihydrochloride

This review article describes the differences in efficacy and side effects between available phosphodiesterase type 5 (PDE-5) inhibitors used for treating erectile dysfunction. The most studied PDE-5 inhibitor is sildenafil.

Topics: Erectile Dysfunction; Humans; Male; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Tadalafil; Vardenafil Dihydrochloride

To determine the effectiveness of the Phosphodiesterase 5 (PDE5) Inhibitors for the treatment of erectile dysfunction in patients with spinal trauma.. A systematic review and meta-analysis comparing PDE5 inhibitors versus placebo were carried out for clinical trials conducted between 1980 and 2014 that evaluated male patients older than 18 years, diagnosed with spinal cord trauma and erectile dysfunction. We designed a search strategy for Medline, CENTRAL, EMBASE and other electronic sources. Two investigators independently and blindly screened the studies for inclusion. A random effect meta-analysis was performed.. Six studies involving 963 patients were included. Male patients over 18 years with ED attributable or subsequent to traumatic spinal cord injury (SCI) were included from these studies. In 4 of these studies, patients were randomized to the treatment group receiving sildenafil and the comparison group was placebo. Out of the remaining 2 trials, one compared tadalafil against the placebo and the other vardenafil versus placebo. The improvement on SCIs with PDE5 inhibitors was found to be large (standardized mean difference 0.71; 95% CI 0.39-1.03), with a high heterogeneity (I2 = 74.4%).. PDE5 inhibitors are effective for the treatment of erectile dysfunction secondary to SCI.

Topics: Adult; Aged; Carbolines; Erectile Dysfunction; Humans; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Randomized Controlled Trials as Topic; Sildenafil Citrate; Spinal Cord Injuries; Tadalafil; Treatment Outcome; Vardenafil Dihydrochloride; Young Adult

We carried out a systematic review and meta-analysis to assess the efficacy and safety of phosphodiesterase type 5 (PDE5) inhibitors for treating erectile dysfunction (ED) after bilateral nerve-sparing radical prostatectomy (BNSRP). A literature review was performed to identify all published randomised double-blind, placebo-controlled trials of PDE5 inhibitors for the treatment of ED after BNSRP. The search included the following databases: MEDLINE, EMBASE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. Six publications involving a total of 1678 patients were used in the analysis, including six RCTs that compared PDE5 inhibitors (tadalafil, sildenafil, avanafil and vardenafil) with placebo. Co-primary efficacy end points: International Index of Erectile Function-Erectile Function (IIEF-EF) domain score [the standardised mean difference (SMD) = 4.04, 95% confidence interval (CI) = 2.87-5.22, P < 0.00001]; successful vaginal penetration (SEP2) [the odds ratio (OR) = 14.87, 95%CI = 4.57-48.37, P < 0.00001]; and successful intercourse (SEP3) (OR = 47, 95%CI = 3-13.98, P < 0.00001) indicated that PDE5 inhibitors was more effective than the placebo. Specific adverse events with PDE5 inhibitors included headache (12.08%), dyspepsia (6.76%) and flushing (6.52%), which were significantly less likely to occur with placebo. This meta-analysis indicates that PDE5 inhibitors to be an effective and well-tolerated treatment for ED after BNSRP.

Topics: Erectile Dysfunction; Humans; Male; Organ Sparing Treatments; Peripheral Nerves; Phosphodiesterase 5 Inhibitors; Postoperative Complications; Prostatectomy; Pyrimidines; Sildenafil Citrate; Tadalafil; Treatment Outcome; Vardenafil Dihydrochloride

Phosphodiesterase type 5 (PDE-5) hydrolyzes cyclic guanylate monophosphate (cGMP) specifically to 5' GMP, promoting successful corporeal vascular relaxation and penile erection during sexual stimulation. Oral PDE-5 inhibitors such as sildenafil, vardenafil, tadalafil, and avanafil have provided noninvasive, effective, well-tolerated treatment for erectile dysfunction (ED) patients and, at the same time, stimulated both academic and clinical interests. Lately, some oral PDE-5 inhibitors were released as low-dose preparations with the concept of potential daily administration and long-term use.. To highlight the possible potential implications of low-dose long-term use of PDE-5 inhibitors.. A systematic review was carried out until December 2015 based on a search of all concerned articles in MEDLINE, medical subjects heading (MeSH) databases, Scopus, The Cochrane Library, EMBASE, and CINAHL databases without language restriction. Key words used to assess the outcome and estimates for concerned associations were: PDE-5 inhibitors; erectile dysfunction; low-dose; long-term; sildenafil; tadalafil; vardenafil; avanafil.. Demonstrating different implications for low-dose long-term use of PDE-5 inhibitors.. Low-dose and/or long-term use of PDE-5 inhibitors was shown to put forth beneficial sound effects in different medical implications with potentials that could be extended for different utilities. These implications included sexual, urogenital, cardiovascular, pulmonary, cutaneous, gastrointestinal, and reproductive, as well as neurological disorders. However, it is evident that most potential appliances were carried out experimentally on preclinical studies with off-label indications.. Making use of and exploring low-dose and/or long-term use of several PDE-5 inhibitors for their possible implications seem to be valuable in different medical disorders. Increased knowledge of the drug characteristics, comparative treatment regimens, optimal prescribing patterns, and well-designed clinical trials are needed before these agents can be recommended for use.

Topics: Dose-Response Relationship, Drug; Erectile Dysfunction; Humans; Male; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Tadalafil; Treatment Outcome; Vardenafil Dihydrochloride

Erectile dysfunction is usually of vascular origin and is frequently encountered in men with cardiovascular disease. The introduction of phosphodiesterase-5 inhibitors has revolutionized the management of patients with erectile dysfunction. Currently available phosphodiesterase-5 inhibitors have distinct pharmacokinetic and pharmacodynamic properties, thus permitting for tailoring sexual therapy according to patient characteristics and needs. Phosphodiesterase-5 inhibitors possess vasorelaxing properties and exert systemic hemodynamic effects, which need to be taken into account when other cardiovascular drugs are co-administered. Special caution is needed with alpha-blockers, while the co-administration with nitrates is contra-indicated due to the risk of life-threatening hypotension. This review presents the advent of sexual therapy, describes the mechanism of action and the specific characteristics of commercially available phosphodiesterase-5 inhibitors, summarizes the efficacy and safety of these drugs with special emphasis on the cardiovascular system, and discusses the clinical criteria used for the selection of each drug for the individual patient.

Topics: Cardiovascular Diseases; Drug Incompatibility; Erectile Dysfunction; Humans; Male; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Tadalafil; Vardenafil Dihydrochloride; Vasodilator Agents

Vardenafil (VAR) is synthetic, highly selective, and potent inhibitor of phosphodiesterase-5 which competitively inhibits cyclic guanosine monophosphate (cGMP) hydrolysis and thus increases cGMP levels. It is clinically approved for treatment of erectile dysfunction in men, including diabetic and postprostatectomy patients. Several methods of VAR synthesis are included in this review. UV spectroscopy of VAR showed a λmax of approximately 270nm, and IR spectroscopy principal peaks were observed at 3420 (NH), 1724 (CO), 1600 (CC, and CN), 1491 (CHCH) cm(-1). Characteristic carbonyl (CO) carbon was observed in nuclear magnetic resonance spectroscopy at 162.44ppm. The molecular mass was observed at m/z=488.9 (molecular weight=488.2) and the fragmentation pattern was studied using ion trap mass spectrometry. In addition, different analytical methods for determination of vardenafil are also described in this profile. Pharmacokinetic properties of VAR have great impact on efficacy. VAR is rapidly absorbed and slowly metabolized, with an absolute bioavailability of 15%. It is extensively metabolized by CYP3A4 into several metabolites, the most pharmacologically active of which is N-desethyl VAR (M1). The elimination half-life of VAR and M1 is about 4-5h. VAR is primarily excreted as metabolites in the feces and to a small extent in urine. VAR is generally well tolerated, with a favorable safety profile and few transient side effects, including headache, flushing, dyspepsia, and rhinitis.

Topics: Animals; Chemistry, Pharmaceutical; Erectile Dysfunction; Humans; Imidazoles; Male; Molecular Structure; Phosphodiesterase 5 Inhibitors; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

Phosphodiesterase-5 (PDE5) inhibitors, such as sildenafil, tadalafil and vardenafil are first line treatment for erectile dysfunction (ED). These PDE5 inhibitors are known to increase cyclic guanosine monophosphate (cGMP) concentrations in the smooth muscle cells of the corpora cavernosa penis by inhibiting PDE5, leading to smooth muscle relaxation. This mode of action is also believed to result in prostatic smooth muscle relaxation and to improve lower urinary tract symptoms (LUTS). Randomized controlled trials have shown beneficial effects on LUTS and on objective parameters such as maximum urinary flow rate (tadalafil). Based on these data tadalafil was recently approved for treatment of patients with male LUTS; however, the mechanisms leading to improvement of symptoms are still under debate.

Topics: Carbolines; Controlled Clinical Trials as Topic; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Lower Urinary Tract Symptoms; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Prostatic Hyperplasia; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Urodynamics; Vardenafil Dihydrochloride

Optimal pharmacologic management of diseases comorbid with erectile dysfunction (ED), such as cardiovascular disease, depression, diabetes, dyslipidemia, hypertension, and benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS), is dependent upon long-term treatment compliance and may be complicated by poor adherence to medication use. ED may contribute to poor adherence to medication use because poor quality erectile function may be an unwanted adverse effect of antihypertensives, antidepressants, and 5-α reductase inhibitors for treatment of BPH/LUTS. Diminished erectile spontaneity, rigidity, and/or sustaining capability also negatively affects mood, self-esteem, and confidence, which compromise motivation to be compliant with medications that treat diseases comorbid with ED.. Literature review was performed to explore the role of ED diagnosis and effective treatment in enhancing overall management of selected ED comorbidities, highlighting the role of medication adherence.. Several PubMed searches were performed.. Diagnosis and successful treatment of concomitant ED may promote improved adherence and management of comorbid diseases. Concomitant ED management may improve treatment outcome, decrease healthcare costs, and possibly prevent or even improve deterioration in medical conditions comorbid with ED. Because ED is a silent marker and predictor of comorbidities, especially cardiovascular disease, earlier diagnosis of ED may provide an opportunity to prevent future cardiovascular events. In men presenting with complaints of ED, screening for, monitoring, and appropriately treating diseases that are comorbid with ED is essential. Screening for and appropriately treating ED is important for enhanced life quality and improved motivation in men with existing ED comorbidities or risk factors.. Appropriate management of ED and its risk factors may have beneficial effects on diseases that are comorbid with ED, and vice versa, most likely via shared pathophysiological pathways. Clinicians may need to consider men's health overall, of which sexual health is a central component, in order to provide optimal disease management.

Topics: 5-alpha Reductase Inhibitors; Affect; Antidepressive Agents; Antihypertensive Agents; Carbolines; Comorbidity; Drug Therapy, Combination; Erectile Dysfunction; Humans; Imidazoles; Long-Term Care; Male; Medication Adherence; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Self Concept; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) is the most frequently treated male sexual dysfunction worldwide. ED is a chronic condition that exerts a negative impact on male self-esteem and nearly all life domains including interpersonal, family, and business relationships.. The aim of this study is to provide an updated overview on currently used and available conservative treatment options for ED with a special focus on their efficacy, tolerability, safety, merits, and limitations including the role of combination therapies for monotherapy failures.. The methods used were PubMed and MEDLINE searches using the following keywords: ED, phosphodiesterase type 5 (PDE5) inhibitors, oral drug therapy, intracavernosal injection therapy, transurethral therapy, topical therapy, and vacuum-erection therapy/constriction devices. Additionally, expert opinions by the authors of this article are included.. Level 1 evidence exists that changes in sedentary lifestyle with weight loss and optimal treatment of concomitant diseases/risk factors (e.g., diabetes, hypertension, and dyslipidemia) can either improve ED or add to the efficacy of ED-specific therapies, e.g., PDE5 inhibitors. Level 1 evidence also exists that treatment of hypogonadism with total testosterone < 300 ng/dL (10.4 nmol/L) can either improve ED or add to the efficacy of PDE5 inhibitors. There is level 1 evidence regarding the efficacy and safety of the following monotherapies in a spectrum-wide range of ED populations: PDE5 inhibitors, intracavernosal injection therapy with prostaglandin E1 (PGE1, synonymous alprostadil) or vasoactive intestinal peptide (VIP)/phentolamine, and transurethral PGE1 therapy. There is level 2 evidence regarding the efficacy and safety of the following ED treatments: vacuum-erection therapy in a wide range of ED populations, oral L-arginine (3-5 g), topical PGE1 in special ED populations, intracavernosal injection therapy with papaverine/phentolamine (bimix), or papaverine/phentolamine/PGE1 (trimix) combination mixtures. There is level 3 evidence regarding the efficacy and safety of oral yohimbine in nonorganic ED. There is level 3 evidence that combination therapies of PDE5 inhibitors + either transurethral or intracavernosal injection therapy generate better efficacy rates than either monotherapy alone. There is level 4 evidence showing enhanced efficacy with the combination of vacuum-erection therapy + either PDE5 inhibitor or transurethral PGE1 or intracavernosal injection therapy. There is level 5 evidence (expert opinion) that combination therapy of PDE5 inhibitors + L-arginine or daily dosing of tadalafil + short-acting PDE5 inhibitors pro re nata may rescue PDE5 inhibitor monotherapy failures. There is level 5 evidence (expert opinion) that adding either PDE5 inhibitors or transurethral PGE1 may improve outcome of penile prosthetic surgery regarding soft (cold) glans syndrome. There is level 5 evidence (expert opinion) that the combination of PDE5 inhibitors and dapoxetine is effective and safe in patients suffering from both ED and premature ejaculation.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Alprostadil; Carbolines; Drug Therapy, Combination; Erectile Dysfunction; Humans; Hypogonadism; Imidazoles; Male; Middle Aged; Penile Erection; Phosphodiesterase 5 Inhibitors; Piperazines; Pyrimidines; Risk Factors; Sulfonamides; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Yohimbine

To determine the efficacy of phosphodiesterase inhibitors for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH).. MEDLINE and PubMed were searched from January 1, 2000, to October 31, 2012, using the MeSH terms phosphodiesterase inhibitor, lower urinary tract symptoms, benign prostatic hyperplasia, sildenafil, vardenafil, and tadalafil. Additional articles were obtained from references identified in the original search.. English-language randomized controlled trials and review articles were evaluated.. Men with BPH commonly experience lower urinary tract symptoms (LUTS) such as urgency, frequency, nocturia, and dribbling. α-Adrenergic antagonists have been the mainstay of medical treatment of LUTS but are associated with adverse effects such as orthostatic hypotension, dizziness, and sexual dysfunction. The 5-α reductase inhibitors are associated with sexual dysfunction, and treatment effects may be delayed for 6-12 months. Phosphodiesterase type 5 (PDE-5) inhibitors are effective for the treatment of erectile dysfunction (ED), and large-scale epidemiologic studies suggest a strong link between LUTS and ED. The available PDE-5 inhibitors (sildenafil, tadalafil, and vardenafil) have shown efficacy in the treatment of LUTS in several randomized controlled trials in men with and without concomitant ED.. PDE-5 inhibitors consistently reduce LUTS associated with BPH. These medications may offer advantages over conventional therapies such as rapid onset of action, fewer adverse effects, and enhanced sexual function. Quality of life improvements have also been realized in men with BPH who receive PDE-5 inhibitors.

Topics: Adrenergic alpha-Antagonists; Carbolines; Drug Resistance; Drug Therapy, Combination; Erectile Dysfunction; Humans; Imidazoles; Lower Urinary Tract Symptoms; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Prostate; Prostatic Hyperplasia; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Phosphodiesterase type 5 inhibitors (PDE5-Is) are currently the first-line therapy for erectile dysfunction (ED), but available studies investigating the comparative effects of different PDE5-Is are limited.. To compare the efficacy and safety of different classes of oral PDE5-Is for ED.. A systematic search was performed in PubMed, Cochrane Library, and Embase to identify randomized controlled trials that compared different PDE5-Is or PDE5-Is with a placebo for ED. The methodological quality of included studies was appraised with the Cochrane Collaboration bias appraisal tool, and the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation system.. A total of 118 trials (31 195 individuals) were included. There was no major difference in the results between the traditional meta-analysis and the network meta-analysis. Network meta-analysis demonstrated that PDE5-Is were superior to placebo to improve erectile function. Compared with tadalafil (relative risk [RR]: 0.61; 95% confidence interval [CI], 0.33-0.90) and vardenafil (RR: 0.63; 95% CI, 0.35-0.92), avanafil was less effective on Global Assessment Questionnaire question 1. Tadalafil was more effective than vardenafil (mean difference [MD]: 1.49; 95% CI, 0.50-2.50) and udenafil (MD: -1.84; 95% CI, -3.31 to -0.33) as measured by the erectile function domain of the International Index of Erectile Function. For all efficacy outcomes, the absolute effects and the rank tests indicated that tadalafil and vardenafil were the most effective agents. After adjusting for dosage, the conclusion remained the same. Safety analysis showed there was no major difference among different agents.. In recommended doses, oral PDE5-Is are more effective than placebo for ED, and tadalafil seems to be the most effective agent, followed by vardenafil. PDE5-Is are generally safe and well tolerated, and there is no major difference on the safety profile.

Topics: Administration, Oral; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Odds Ratio; Penile Erection; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Risk Assessment; Risk Factors; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

As men age, there is an increase in the frequency of pathologic diseases affecting the genitourinary tract. Most notable among these changes are the rising prevalence of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) and erectile dysfunction (ED). The pathogenesis of these conditions seems to be multifactorial and includes age-related changes in the nervous system and neuroregulatory factors, such as nitric oxide and RhoA/Rho-kinase. Various pharmacologic agents that target these pathways, such as α-blockers and PDE-5is, underscore the contribution of neuroregulatory factors on the development of LUTS/BPH and ED.

Topics: Age Factors; Aged; Aged, 80 and over; Aging; Carbolines; Disease Progression; Erectile Dysfunction; Humans; Imidazoles; Lower Urinary Tract Symptoms; Male; Men's Health; Middle Aged; Neurotransmitter Agents; Piperazines; Prognosis; Prostatic Hyperplasia; Purines; Receptors, Neurotransmitter; Risk Assessment; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Vardenafil orodispersible tablet (ODT) is a supralingual formulation of vardenafil that is available for the on-demand treatment of erectile dysfunction. The pharmacokinetics of vardenafil ODT are not equivalent to those of the vardenafil film-coated tablet in that the ODT formulation provides consistently greater vardenafil systemic exposure. Therefore, the two formulations are not interchangeable. The efficacy of on-demand vardenafil ODT 10 mg was established in the POTENT I and II studies, which were 6-week, randomized, double-blind, multinational trials in men with erectile dysfunction of at least 6 months duration. In both trials, vardenafil ODT improved erectile function significantly more than placebo, as indicated by International Index of Erectile Function-Erectile Function subscale scores at week 12 and overall erection success rates during treatment according to responses to questions 2 and 3 of the Sexual Encounter Profile (coprimary endpoints). In a pooled analysis of both trials, vardenafil ODT improved erectile function regardless of age, severity of erectile dysfunction at baseline or the presence or absence of underlying medical conditions. Vardenafil ODT was generally well tolerated in clinical trials, including in men aged ≥65 years, and adverse events were mostly mild or moderate in severity.

Topics: Administration, Oral; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Randomized Controlled Trials as Topic; Sulfones; Tablets; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Several randomized controlled trials (RCTs) on phosphodiesterase type 5 inhibitors (PDE5-Is) have showed significant improvements in both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in men affected by one or both conditions, without a significant increase in adverse events. However, the results are inconsistent.. Perform a systematic review and meta-analysis of available prospective and cross-sectional studies on the use of PDE5-Is alone or in combination with α1-adrenergic blockers in patients with LUTS/benign prostatic hyperplasia (BPH).. A systematic search was performed using the Medline, Embase, and Cochrane Library databases through September 2011 including the combination of the following terms: LUTS, BPH, PDE5-Is, sildenafil, tadalafil, vardenafil, udenafil, α-blockers, and α1-adrenergic blocker. The meta-analysis was conducted according to the guidelines for observational studies in epidemiology.. Of 107 retrieved articles, 12 were included in the present meta-analysis: 7 on PDE5-Is versus placebo, with 3214 men, and 5 on the combination of PDE5-Is with α1-adrenergic blockers versus α1-adrenergic blockers alone, with 216 men. Median follow-up of all RCTs was 12 wk. Combining the results of those trials, the use of PDE5-Is alone was associated with a significant improvement of the International Index of Erectile Function (IIEF) score (+5.5; p<0.0001) and International Prostate Symptom Score (IPSS) (-2.8; p<0.0001) but not the maximum flow rate (Q(max)) (-0.00; p=not significant) at the end of the study as compared with placebo. The association of PDE5-Is and α1-adrenergic blockers improved the IIEF score (+3.6; p<0.0001), IPSS score (-1.8; p = 0.05), and Q(max) (+1.5; p<0.0001) at the end of the study as compared with α-blockers alone.. The meta-analysis of the available cross-sectional data suggests that PDE5-Is can significantly improve LUTS and erectile function in men with BPH. PDE5-Is seem to be a promising treatment option for patients with LUTS secondary to BPH with or without ED.

Topics: Adrenergic alpha-Antagonists; Carbolines; Drug Therapy, Combination; Erectile Dysfunction; Humans; Imidazoles; Lower Urinary Tract Symptoms; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Prostatic Hyperplasia; Purines; Pyrimidines; Sildenafil Citrate; Sulfonamides; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

The scale at which erectile dysfunction (ED) medicines are obtained outside of the official health system rivals and possibly exceeds legitimate sales. According to literature a high-risk segment of this market is occupied by adulterated food supplements. The principle adulterants identified were structural analogues of the registered ED drugs sildenafil, tadalafil, and vardenafil. Currently, at least 46 different analogues have been reported and still more are expected. The intellectual origin of analogues was found in patent literature which described the drug discovery process. Patent literature offers a flexible approach to synthesize hundreds of analogues. Most of the analogues currently known had long been disclosed in patent literature. Screening for (new) analogues is best carried out by using advanced LC-MS/MS techniques that focus on marker fragment ions. Analogues are experimental drugs in essence because most have no known efficacy or safety profile. Their use in seemingly harmless food supplements is expected to cause serious adverse effects. However, few reports have emerged in literature on actual harm. Considering the exposure to analogues and their adverse effects being unknown a gross underreporting of complaints is expected.

Topics: Carbolines; Chemistry Techniques, Analytical; Cyclic Nucleotide Phosphodiesterases, Type 5; Dietary Supplements; Drug Contamination; Erectile Dysfunction; Humans; Imidazoles; Ions; Male; Models, Chemical; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Men with erectile dysfunction (ED) are typically older and have one or more underlying cardiovascular conditions.. To determine the efficacy and safety of a new orodispersible tablet (ODT) formulation of vardenafil for the treatment of ED, and whether age, or the presence of underlying conditions affects treatment outcomes.. This is an integrated analysis of data from two phase III, double-blind, multicenter, randomized, parallel-group, placebo-controlled studies that compared 10 mg on-demand vardenafil ODT with placebo in a general population of men with ED, stratified so that approximately 50% of patients were aged ≥ 65 years. Results were reported by age (<6 5 vs. ≥ 65 years) and presence/absence of diabetes, dyslipidemia, or hypertension.. Primary measures were the erectile function domain of the International Index of Erectile Function (IIEF-EF) and Sexual Encounter Profile questions 2 (SEP2) and 3 (SEP3).. Of the 701 men randomized (51% aged ≥ 65 years), 686 were included in the intent-to-treat population (placebo, n = 334; vardenafil ODT, n = 352). Vardenafil ODT was significantly superior to placebo for all primary efficacy measures, regardless of age, baseline ED severity, or underlying condition (P < 0.0001 for vardenafil vs. placebo for each endpoint). IIEF-EF scores and SEP2/3 success rates in older patients and men with underlying conditions were not significantly different to those of younger patients or men without underlying conditions. Adverse events (AEs) were mostly mild to moderate in severity, occurring with higher incidence in the vardenafil vs. placebo group. The most frequently reported drug-related AEs in the vardenafil group were headache, flushing, nasal congestion, dizziness, and dyspepsia, consistent with the known safety profile of phosphodiesterase type 5 inhibitors.. Vardenafil ODT significantly improves erectile function in men with ED regardless of age, baseline ED severity, or underlying condition.

Topics: Age Factors; Aged; Biological Availability; Comorbidity; Diabetes Mellitus; Dosage Forms; Double-Blind Method; Dyslipidemias; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Randomized Controlled Trials as Topic; Sulfones; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) is an important worldwide health issue that has a significant negative impact on the quality of life and life satisfaction of both the affected individual and his partner. Here we review the prevalence of ED in Asia, associated factors that may influence sexual attitudes and sexual behaviours, and randomized clinical trials (RCTs) of phosphodiesterase-5 (PDE-5) inhibitors to evaluate the clinical efficacy and safety of PDE-5 inhibitors in Asian men. We searched for English-language articles in MEDLINE and PubMed from January 2000 to September 2010. Our results showed that the overall reported prevalence rate of ED in Asia ranged widely, from 2% to 88%. This finding indicates that ED is a common and major health problem in this region. However, sociocultural and economic factors in Asia prevent people from seeking and obtaining appropriate medical care. We found reports on five kinds of PDE-5 inhibitors for the management of ED: sildenafil, vardenafil, tadalafil, udenafil and mirodenafil. The results of RCTs showed that these five PDE-5 inhibitors are more effective than placebo in improving erectile function in Asian men with ED and that these drugs have similar efficacy and safety profiles.

Topics: Adult; Aged; Asia; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug-Related Side Effects and Adverse Reactions; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Prevalence; Purines; Pyrimidines; Pyrimidinones; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfonamides; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Topics: Erectile Dysfunction; Humans; Imidazoles; Male; Penile Erection; Phosphodiesterase 5 Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Erectile dysfunction (ED) is the most common sexual problem in men. The incidence increases with age and affects up to one third of men throughout their lives. It causes a substantial negative impact on intimate relationships, quality of life, and self-esteem. History and physical examination are sufficient to make a diagnosis of ED in most cases, because there is no preferred, first-line diagnostic test. Initial diagnostic workup should usually be limited to a fasting serum glucose level and lipid panel, thyroid-stimulating hormone test, and morning total testosterone level. First-line therapy for ED consists of lifestyle changes, modifying drug therapy that may cause ED, and pharmacotherapy with phosphodiesterase type 5 inhibitors. Obesity, sedentary lifestyle, and smoking greatly increase the risk of ED. Phosphodiesterase type 5 inhibitors are the most effective oral drugs for treatment of ED, including ED associated with diabetes mellitus, spinal cord injury, and antidepressants. Intraurethral and intracavernosal alprostadil, vacuum pump devices, and surgically implanted penile prostheses are alternative therapeutic options when phosphodiesterase type 5 inhibitors fail. Testosterone supplementation in men with hypogonadism improves ED and libido, but requires interval monitoring of hemoglobin, serum transaminase, and prostate-specific antigen levels because of an increased risk of prostate adenocarcinoma. Cognitive behavior therapy and therapy aimed at improving relationships may help to improve ED. Screening for cardiovascular risk factors should be considered in men with ED, because symptoms of ED present on average three years earlier than symptoms of coronary artery disease. Men with ED are at increased risk of coronary, cerebrovascular, and peripheral vascular diseases.

Topics: Aged; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Risk Reduction Behavior; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Topics: Antihypertensive Agents; Contraindications; Coronary Disease; Drug Interactions; Drug Therapy, Combination; Erectile Dysfunction; Female; Humans; Hypertension, Pulmonary; Hypotension; Imidazoles; Male; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

The immediate objective of phosphodiesterase type 5 (PDE5) inhibitor treatment is to restore the ability of a man to achieve and/or maintain an erection adequate for sexual intercourse. As erectile dysfunction (ED) generally develops in the second half of life, the ultimate objective generally is not procreation, but quality of sexual life. Indeed, ED is known to impair quality of life considerably; two-thirds of men report that ED has impaired their self-esteem and nearly a third claim that it has damaged the relationship with their partner. It follows that the therapeutic success of PDE5 inhibition has an important subjective component, which is compounded by the subjective nature and complexity of sexual life in humans. This makes it very difficult for physicians to be certain that they have selected the optimal therapy for a couple, even after a thorough evaluation. The 2007 European Association of Urology Guidelines stress the importance of educating the patient and claim that 'the patient will choose the final drug after his own experience'. However, PDE5 inhibitors are typically used twice a week, so a patient would have to spend approximately 3 months trying the various compounds and dosages to achieve adequate exposure to all three PDE5 inhibitors; this would seem an unrealistic strategy in normal clinical practice. The acknowledgement that the patient has an important role in therapeutic decisions for ED has fuelled interest in the concept of patient preference. It has been established that patient preference depends on three factors, i.e. personal characteristics, e.g. age, duration of ED, frequency and dynamics of sexual relations, and the characteristics of their partners, e.g. age, menopausal status and level of interest in sexual activity and medication profile. Medication features of interest include efficacy in terms of quality of erection, consistency of effects, rapid onset of action, long duration of action, side-effect profile and route of administration; drug costs must also be considered if the medicinal product is not reimbursed.

Topics: Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Patient Satisfaction; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Purines; Quality of Life; Self Concept; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

The majority of men with spinal cord injury (SCI) require chronic treatment for erectile dysfunction (ED), but most of them, prior to taking phosphodiesterase type 5 (PDE5) inhibitors, stopped therapy due to side-effects or low compliance rate.. Analysis of literature on oral PDE5 inhibitors in individuals with SCI and ED in order to evaluate how much their release changed the management of ED in SCI subjects and what remains to be seen of their potential or limits.. Questionnaires on sexual function.. 18 internationally published clinical studies that enrolled SCI males treated with at least one of the PDE5 inhibitors were analyzed.. The small numbers of papers with large and diverse outcome measures did not consent a meta-analysis of treatment results. 705 used sildenafil, 305 vardenafil and 224 tadalafil. Median age was less than 40 years. Only 1 study excluded tetraplegic individuals. For measures of ED evaluated, 11 out of 13 studies reported a significant statistical improvement with PDE5 inhibitors versus placebo or erectile baseline (P < 0.01, or p < 0.005). The most frequent predicable factor for the therapeutic success of PDE5 inhibitors was upper motoneuron lesion. Statistical impact on ejaculation success rates was shown in at least one paper for all PDE5 inhibitors (p < 0.05). Overall, 15 patients, (7 using sildenafil), discontinued the therapies due to drawbacks. Only 1 sildenafil study reported a follow-up maximum of 24 months.. Literature suggests that all oral PDE5 inhibitors represent a safe and effective treatment option for ED caused by SCI. Further research is needed on head-to-head comparative trials and SCI patient preference for these drugs; their impact on ejaculation and orgasm function, their early use after SCI for increasing the recovery rate of a spontaneous erection, and their effectiveness and tolerability in the long-term are still to be investigated.

Topics: Administration, Oral; Adolescent; Adult; Aged; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Reproduction; Sildenafil Citrate; Spinal Cord Injuries; Sulfones; Surveys and Questionnaires; Tadalafil; Triazines; Vardenafil Dihydrochloride; Young Adult

To critically review the physiological roles of phosphodiesterase-5 (PDE5), to explain and support the putative impact and clinical significance of PDE5 inhibitors (PDE5-Is) in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and erectile dysfunction (ED), both highly prevalent in men aged > or =50 years, as PDE5-Is are very effective as a first-line therapy for ED, and attractive for further physiological functional investigations.. We searched Medline for peer-reviewed articles in English, from 1991 to 2008, to provide a critical contemporary review of PDE5 pertaining to the potential interest of findings supporting a role for PDE5-Is in LUTS due to BPH. The selection of papers was based on the relevance of subject matter. A critical analysis of available fundamental and clinical data is reported.. Several studies assessed the role of the nitric oxide/cGMP signalling pathway in the regulation of the prostate tone, with the support of clinical observations. PDE5-Is can also represent a potential mode of action allowing the targeting of transcriptional activity implicated in the regulation of the progression of the inflammatory process involved in BPH. PDE5-Is can inhibit human stromal cell proliferation of the prostate mediated by cGMP accumulation. New targeting hypotheses of pathophysiological processes are also reported.. There is evidence that LUTS and ED are strongly linked. This analysis of the regulatory basis of PDE5 biology could indicate several directions of investigation. However, it is necessary to devise well-designed large prospective studies that would produce significant data before this approach becomes a standard of care.

Topics: Aged; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prostatic Hyperplasia; Prostatism; Purines; Quality of Life; Quinazolines; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Vardenafil is a short-acting PDE5 inhibitor used in the treatment of male erectile dysfunction. It is the most potent and specific of the three commercially available PDE5 inhbitors, which may decrease incidence of side effects, although this has not been demonstrated clinically. Although its efficacy in the treatment of erectile dysfunction has been demonstrated in several studies, recent and continuing studies have shown vardenafil's promise as an effective agent in penile rehabilitation, decreasing lower urinary tract symptoms resulting from benign prostatic hyperplasia and management of pulmonary hypertension.

Topics: Animals; Erectile Dysfunction; Humans; Hypertension, Pulmonary; Imidazoles; Male; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Prostatic Hyperplasia; Sulfones; Triazines; Vardenafil Dihydrochloride

Many men with erectile dysfunction (ED) also have associated underlying cardiovascular and metabolic conditions, for which they are likely to be taking medication. Therefore, cardiovascular safety and potential drug interactions are two of the major concerns when using PDE-5 inhibitors in these patients. The PDE-5 inhibitor, vardenafil, is characterized by a rapid onset of action, increased duration of erection, high rates of first-dose success and reliable efficacy that can be maintained with continued use. In both clinical trials and real-life observational studies, vardenafil has demonstrated a favorable efficacy and safety profile in men with ED, including those with associated underlying conditions such as diabetes, hypertension and dyslipidemia. Importantly, the concomitant use of medication for these conditions is not associated with any noteworthy changes in the efficacy and safety of vardenafil. The evidence presented in this review supports the use of vardenafil as a first-line treatment for men with ED, including those with underlying conditions.

Topics: Aging; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Complications; Drug Interactions; Erectile Dysfunction; Humans; Imidazoles; Male; Metabolic Syndrome; Phosphodiesterase Inhibitors; Piperazines; Prevalence; Risk Factors; Sulfones; Triazines; Vardenafil Dihydrochloride

In recent years, more and more attention has been drawn to the role of phosphodiesterase 5 (PDE5) in penile erection. The cyclic nucleotide (cGMP) signaling pathway mediates the smooth-muscle relaxing effect of nitric oxide necessary for normal erectile function. Down-regulation of this pathway is the pathological pivot of many forms of erectile dysfunction (ED) and leads to the development of some chronic diseases. Therapeutic outcomes have shown that vardenafil is effective and safe in the treatment of ED associated with dyslipidemia, hypertension, depression, diabetes, radical retropubic prostatectomy, spinal cord injury, sildenafil failure, renal transplantation, chronic prostatitis and that accompanied by premature ejaculation. Vardenafil provides a reasonable therapeutic alternative for these refractory ED patients. In addition, vardenafil can prolong erectile duration of ED patients.

Topics: Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Vardenafil has demonstrated efficacy for the pharmacological management of erectile dysfunction (ED). Accumulating evidence suggests that ED is frequently associated with underlying cardiovascular and metabolic conditions which are thought to be involved in the aetiology of ED. The present review aims to summarise and discuss the available evidence for the efficacy, safety and tolerability of vardenafil in patients with underlying conditions including diabetes, hypertension and dyslipidaemia.. Relevant articles were identified through a PubMed search of clinical trials and postmarketing surveillance studies of vardenafil in patients with ED including those with diabetes, hypertension and dyslipidaemia.. Across all trials, vardenafil showed good efficacy for the treatment of ED in patients with diabetes, hypertension and dyslipidaemia. Vardenafil also showed a favourable safety and tolerability profile. The concomitant use of medication to treat hypertension or dyslipidaemia was not associated with an increase in adverse events following vardenafil treatment.. The prevalence of both diagnosed and undiagnosed underlying conditions is high among men with ED. The evidence presented in this review suggests that vardenafil is efficacious and well tolerated in patients with ED and diabetes, hypertension and/or dyslipidaemia and can be recommended as first-line treatment for ED in patients with these conditions.

Topics: Cardiovascular Diseases; Diabetes Complications; Dyslipidemias; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Randomized Controlled Trials as Topic; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Review the literature on phosphodiesterase type 5 inhibitors (PDE5-Is), addressing critical issues in their current and future use, assessing unanswered questions, and identifying research needs.. A MEDLINE search was conducted on PDE5-Is, with emphasis on clinical trials and experience, for interpretation and analysis of their present and future role.. Although approximately 40 million patients with erectile dysfunction have been treated successfully worldwide with the three available PDE5-Is, inappropriate instructions, lack of follow-up, and lack of patient-centered care models are the main reasons for "non-response," leading to drop-out rates of >50%. Patients with severe neurologic damage, diabetes mellitus, or severe vascular disease may be resistant to PDE5-Is. Preservation of corporal smooth muscle with chronic administration of PDE5-Is has been reported and substantial evidence indicates that these drugs have beneficial effects on endothelium and cardiovascular function; sildenafil has been approved for the treatment of idiopathic pulmonary hypertension. Improvement of lower urinary tract symptoms in men with benign prostatic hyperplasia after PDE5-I administration has been also suggested.. The data indicate the necessity for (1) exploration of the pharmacologic characteristics of the three PDE5-Is; (2) research on their pharmacologic differences because some actions seems to be drug-specific; (3) development of alternative management strategies, such as chronic, low, everyday doses of PDE5-Is, if the monthly cost is affordable; and (4) clinical trials on use of PDE5-Is to treat other chronic conditions. The door for innovative therapeutic approaches will open, specifically for cross-risk factor treatment with PDE5-Is or their use in combination treatments or new multimodal pills that take advantage of drugs that exert pleiotropic vascular actions.

Topics: Animals; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction is a common multi-factorial complication of diabetes mellitus. Numerous strategies have been tried to overcome this diabetic complication. In recent years, phosphodiesterase type 5 (PDE-5) inhibitors have been introduced in the management of erectile dysfunction.. The objective of this review was to assess the effect of PDE-5 inhibitors on the management of erectile dysfunction in diabetic men.. Studies were obtained from computerised searches of MEDLINE, EMBASE and The Cochrane Library.. Randomised controlled trials, in which treatment with PDE-5 inhibitors was compared to control, in diabetic patients with erectile dysfunction.. Two reviewers independently extracted data and assessed trial quality.. Eight randomised controlled trials were identified. A total 976 men were allocated to receive a PDE-5 inhibitor and 741 were randomised to the control groups. Overall, 80% of the participants suffered from type 2 diabetes mellitus. The weighted mean difference (WMD) for the International Index of Erectile Function (IIEF) questions 3 and 4 (frequency of penetration during and maintaining erection to completion of intercourse) was 0.9 (95% CI 0.8 to 1.1) and 1.1 (95% CI 1.0 to 1.2) at the end of the study period, in favour of the intervention group. The WMD for the IIEF erectile dysfunction domain at the end of the study period was 6.6 (95% CI 5.2 to 7.9) in favour of the PDE-5 inhibitors arm. The relative risk (RR) for answering "yes" to a global efficacy question ( "did the treatment improve your erections?") was 3.8 (CI 95% 3.1 to 4.5) in the PDE-5 inhibitors compared with the control arm. The WMD between the percentage of successful attempts in the PDE-5 inhibitors and in the control arm was 26.7 (95% CI 23.1 to 30.3). Mortality was not reported in any of the included trials. Adverse cardiovascular effects were reported in one study. Headache was the most frequent adverse event reported, flushing was the second most common event, with upper respiratory tract complaints and flu like syndromes, dyspepsia, myalgia, abnormal vision and back pain also reported in a descending order of frequency. The overall risk ratio for developing any adverse reaction was 4.8 (CI 95% 3.74 to 6.16) in the PDE-5 inhibitors arm as compared to the control.. Sufficient evidence exists that PDE-5 inhibitors form a care that improves erectile dysfunction in diabetic men.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Diabetic Angiopathies; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

To assess the influence of vardenafil on treatment satisfaction in men with erectile dysfunction (ED) and their female partners.. 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.. 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).. Vardenafil significantly improved treatment satisfaction in men with ED, and in their partners. The results provide further evidence of the validity of the TSS.

Topics: Double-Blind Method; Erectile Dysfunction; Female; Humans; Imidazoles; Male; Patient Satisfaction; Personal Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Randomized Controlled Trials as Topic; Sexual Partners; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Vardenafil is a selective phosphodiesterase-5 inhibitor approved for the treatment of erectile dysfunction. It was found to be effective in a high percentage of patients and a broad spectrum of underlying conditions. It potentiates the increase in intracellular cGMP in the corpora cavernosa in response to sexual stimuli, resulting in enhanced and prolonged erections. The overall tolerability and safety profile is acceptable, with headache, flushing, rhinitis and dyspepsia being the major reported side effects. Importantly, tolerability and safety in cardiovascular patients seems to be good with no significant increase in cardiovascular events that could be directly attributed to the pharmacologic agent. Only mild blood-pressure lowering effects were observed in healthy individuals, as well as hypertensive patients on multiple antihypertensive agents. However, special caution is mandatory if vardenafil is administered in combination with alpha-blockers, as significant hypotension might occur. Importantly, any drug serving as a nitric oxide donor is contraindicated in combination with vardenafil.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

To review the evidence evaluating the efficacy of vardenafil in subgroups of hypertensive patients with erectile dysfunction (ED).. Meta-analysis of randomized, double-blinded, placebo-controlled, flexible-dose vardenafil clinical trials that were >or=12 weeks in duration evaluated men with a >or=6-month history of ED and required a >or=50% failure rate in baseline sexual attempts. The primary endpoints analyzed were the erectile function domain of the International Index of Erectile Function questionnaire (IIEF-EF) and Sexual Encounter Profile questions 2 (SEP2) and 3 (SEP3).. Eight clinical trials were included (n = 2427 patients) consisting of 839 patients (35%) with a self-reported diagnosis of hypertension (HTN): 498 in the vardenafil and 341 in the placebo groups. Vardenafil's efficacy was evidenced by an average increase of 8.9 points in the IIEF-EF (95% CI: 7.4, 10.5) at week 12 compared to placebo, with individual trial values ranging from 16.4 to 26.1 and 11.3 to 17.8 for the vardenafil and placebo groups, respectively. Vardenafil also increased success rates for the ability to obtain erections (SEP2) by 32.4% (95% CI: 27.4%, 37.5%) over a 12-week timeframe compared to placebo, with individual trial values ranging from 57.2% to 92.2% for vardenafil and 32.0% to 66.9% for placebo. Similarly, success rates for the ability to maintain erections (SEP3) improved 38.0% (95% CI: 29.5%, 46.6%) compared to placebo, with individual trial values ranging from 41.7% to 88.2% for vardenafil and 20.5% to 51.4% for placebo. Vardenafil was equally efficacious in improving IIEF-EF, SEP2, and SEP3 in those with and without self-reported HTN.. This meta-analysis demonstrated that vardenafil was significantly more efficacious than placebo for the treatment of ED in patients with comorbid HTN and offered similar treatment benefits in patients without HTN.

Topics: Adult; Aged; Double-Blind Method; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Placebos; Randomized Controlled Trials as Topic; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Radical prostatectomy has been the time-honoured and standard treatment option for prostate cancer. Erectile dysfunction (ED) is one of the common quality-of-life issues following radical prostatectomy. The recovery of potency following radical prostatectomy varies from 16% to 86%. Although major modifications in surgical technique appear to be promising, the reported ED rates are still high. The time period required for the recovery of erectile function after surgery varies from 6 to 24 months. During this period of neuropraxia lack of natural erections produces cavernosal hypoxia. This cavernosal hypoxia has been implicated as one of the most important factors in the pathophysiology of ED. Cavernosal hypoxia predisposes to cavernosal fibrosis, ultimately producing venous leak and long-term ED. Interruption of this cascade of events has been the major challenge for physicians. Physicians have several options available for the treatment of ED. However, oral treatment options have quickly become established as first-line treatment options. Sildenafil has been most extensively studied in the radical prostatectomy population. In patients who do not respond to oral therapy alone, standard treatment options (intracavernosal injections, vacuum constriction devices and intraurethral alprostadil) are useful. Use of penile prostheses is one of the oldest treatment options available for the treatment of ED but is used only as a last resort. Initial attempts to promote the earlier recovery of erectile function appear to be promising. However, further confirmatory studies are essential. The roles of gene transfer and growth factors are still in experimental stages. In this review we discuss the epidemiology, pathophysiology and treatment options available for ED following radical prostatectomy.

Topics: Administration, Oral; Aged; Algorithms; Alprostadil; Carbolines; Combined Modality Therapy; Drug Therapy, Combination; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Penile Prosthesis; Phosphodiesterase Inhibitors; Piperazines; Practice Guidelines as Topic; Prostatectomy; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Erectile dysfunction occurs commonly in untreated and treated hypertensive patients, impairing adherence to treatment and quality of life. Furthermore, it is a marker for enhanced risk for cardiovascular disease. Phosphodiesterase type 5 (PDE5) inhibitors, sildenafil, vardenafil, and tadalafil, provide effective treatment of erectile dysfunction. They reduce blood pressure in healthy patients: sildenafil 100 mg, -3.7/-3.6 mm Hg; vardenafil 20 mg, -7.5/-8 mm Hg; and tadalafil 20 mg, -1.6/-0.8 mm Hg. Greater declines in blood pressure with a PDE5 inhibitor may be observed in treated and untreated hypertensive patients. The additive effect of PDE5 inhibitors with one or multiple antihypertensive drugs is modest. alpha(1)-Blockers, except tamsulosin, may result in larger declines in blood pressure and cause orthostatic hypotension. Thus, caution should be exercised by using the lowest doses of proportional, variant(1)-blockers and PDE5 inhibitors in combination. Nitrates in combination with PDE5 inhibitors cause a profound decline in blood pressure and are contraindicated.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Antihypertensive Agents; Blood Pressure; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Dose-Response Relationship, Drug; Drug Therapy, Combination; Erectile Dysfunction; Humans; Hypertension; Hypotension; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vascular Resistance

Three different phosphodiesterase 5 (PDE5) inhibitors are currently available for the treatment of erectile dysfunction: sildenafil, vardenafil and tadalafil. The differences between these 3 are limited: tadalafil has a long duration of action, while vardenafil has a rapid onset of action after intake. Various studies have suggested that there is an improvement in the partners' sex lives when men use a PDE5 inhibitor for erectile dysfunction. The introduction of PDE5 inhibitors has renewed the interest in PDE inhibitors in general, for example in the treatment of pulmonary hypertension. In the near future PDE inhibitors may be used for various disorders as chronic obstructive pulmonary disease, benign prostatic hyperplasia, hypertension and coronary heart disease.

Topics: Carbolines; Coronary Disease; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Prostatic Hyperplasia; Pulmonary Disease, Chronic Obstructive; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Topics: Adult; Alprostadil; Apomorphine; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Penile Erection; Penile Prosthesis; Piperazines; Purines; Sex Counseling; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Yohimbine

This paper reviewed the safety and tolerability of vardenafil in the treatment of erectile dysfunction (ED), including the general, cardiovascular and ocular safety. Results from clinical trials and practice experience demonstrated that vadenafil had good safety and tolerability, whether for general ED population or for difficult-to-treat ED patients, whether as short-term treatment or as long-term therapy.

Topics: Drug Tolerance; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Time Factors; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To assess the efficacy and safety of vardenafil in the treatment of erectile dysfunction (ED) in men of different age groups.. In a retrospective pooled subgroup analysis of randomized, double-blind, placebo-controlled studies, men from the general population with ED received either placebo or vardenafil 5, 10 or 20 mg over 12 weeks. Efficacy variables included the erectile function (EF) domain score from The International Index of Erectile Function, diary response rates to questions on vaginal penetration and maintenance of erection, and positive responses to the Global Assessment Question (GAQ) "Has the treatment you have been taking over the past 4 weeks improved your erections?'. The 1385 men were grouped by age (< 45, 45-64 and > or =65 years).. At 12 weeks the EF domain scores approached 20 with vardenafil and 14 with placebo in men aged > or = 65 years (P < 0.03 vardenafil 5 mg vs placebo, P < 0.001 vardenafil 10 and 20 mg vs placebo). The corresponding scores were 22 and 14 in men aged 45-64 years and up to 24 and 16 in those aged <45 years (P < 0.03 vardenafil 5 mg vs placebo, P < 0.001 vardenafil 10 and 20 mg vs placebo). Vardenafil generated positive GAQ responses in approximately 71%, 76% and 85% of men aged <45, 45-64 and > or = 65 years (P < or = 0.001 vardenafil vs placebo). The corresponding placebo rates were 23%, 25% and 34%. The most common treatment-emergent adverse events were headache, rhinitis, flushing and dyspepsia, which were mild to moderate, transient and unrelated to age.. Vardenafil is an effective and generally well-tolerated treatment for ED, irrespective of age.

Topics: Adult; Aged; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Multicenter Studies as Topic; Phosphodiesterase Inhibitors; Piperazines; Randomized Controlled Trials as Topic; Retrospective Studies; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

More than one-third of men may experience erectile dysfunction (ED) after nerve-sparing radical retropubic prostatectomy. A recent study has shown that vardenafil, a phosphodiesterase 5 inhibitor, could significantly improve the key indices of erectile function in men after unilateral or bilateral nerve-sparing radical retropubic prostatectomy. Few adverse events were observed in the study.

Topics: Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Postoperative Complications; Prostatectomy; Randomized Controlled Trials as Topic; Spheroids, Cellular; Sulfones; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) affects up to 50% of men, between 40 and 70 years of age. In the first major trial of sildenafil in ED, at 24 weeks, improved erections were reported by 77 and 84% of men taking sildenafil 50 and 100mg, respectively. Subsequently, sildenafil has been reported to be effective in men with ED associated with diabetes and prostate cancer, and in psychogenic ED. Sildenafil is safe in men with coronary artery disease, provided it is not used with the nitrates (a contraindication). The most commonly reported adverse effects with sildenafil are headache, flushing and dyspepsia. Vardenafil is more potent and more selective than sildenafil at inhibiting phosphodiesterase-5. Vardenafil is similarly effective to sildenafil in the treatment of ED. The only advantage that vardenafil has over sildenafil is that it does not inhibit phosphodiesterase-6 to alter colour perception, a rare side effect which sometimes occurs with sildenafil. Tadalafil has a longer duration of action than sildenafil and vardenafil. Tadalafil is similarly effective as sildenafil in the treatment of ED. In comparison studies, tadalafil is preferred to sildenafil (50/100mg) by men with ED, possibly because of its longer duration of action. Of the phosphodiesterase inhibitors, tadalafil may displace sildenafil as the drug of choice among men with ED.

Topics: Carbolines; Controlled Clinical Trials as Topic; Cross-Over Studies; Erectile Dysfunction; Humans; Imidazoles; Male; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Significant advances in the pharmacologic treatment of erectile dysfunction (ERD) have occurred in recent years, most notably the introduction of sildenafil, the first oral selective phosphodiesterase type 5 (PDE5) inhibitor, in 1998. Sildenafil quickly gained acceptance by the medical community and the public because of its broad efficacy for different types of ERD and its ease of use. Two PDE5 inhibitors, vardenafil and tadalafil, have since joined sildenafil to compete in the ERD market. A review was conducted by the Drug Information Service of a pharmacy benefits manager (PBM) to determine the relative merits and place in therapy of commonly used ERD drugs as part of drug formulary management process and decision making by the Pharmacy & Therapeutics (P&T) committee.. To provide readers with a comprehensive clinical monograph on ERD drugs written from a managed care perspective.. The PBM clinical monograph is designed to provide health plans with an evidence-based review of drugs, therapeutic classes, and disease states with a managed care focus. For each therapeutic class or disease review, an extensive and thorough literature search of MEDLINE is conducted for efficacy, safety, effectiveness, and humanistic and economic data. Drug/disease-state databases (UptoDate online, MICROMEDEX), U.S. Food and Drug Administration clinical reviews, key Internet sites, medical/pharmacy-related news sites, clinical guidelines, and AMCP dossiers are also reviewed. Formulary drug monographs prepared by the Drug Information Service of the PBM include a critical analysis and summary of disease-oriented and patient-oriented clinical outcomes, effectiveness, and humanistic data. Additional data considered and included in the formulary review process are clinical attributes, patent expirations/generic competition, off-label or pending indications, and pharmacoeconomic data.. Despite the lack of head-to-head comparative studies, all 3 PDE5 inhibitors appear to have equivalent efficacy in the treatment of general ERD and ERD associated with diabetes and postprostatectomy. Sildenafil has additional efficacy data in the management of ERD associated with spinal cord injury and antidepressant medications. Tadalafil has the longest duration of action (up to 36 hours); this feature can be both beneficial (greater sexual spontaneity) or possibly detrimental (greater exposure to drug, delayed adverse events). All 3 PDE5 inhibitors appear to be generally well tolerated and have similar contraindications and warnings. However, vardenafil is the only PDE5 inhibitor with a cardiac conduction precaution. Alprostadil products are recommended in current ERD guidelines as second-line therapy for those who have not responded or cannot take the oral PDE5 inhibitors. Overall, higher clinical efficacy rates are achieved with intracavernous than with transurethral administration.. A large amount of clinical efficacy and safety data has been published since the market launch of sildenafil in 1998. Sildenafil has the greatest body of efficacy and safety evidence. No comparative studies have been conducted with any of the PDE5 inhibitors. Differences in study populations, primary end points, and measurement tools make comparisons difficult. However, all PDE5 inhibitors appear to be roughly equivalent in efficacy, with minor differences in adverse event profiles. Until more comparative data are available, economic considerations will be a significant factor in choosing ERD products for formulary inclusion.

Topics: Carbolines; Drug Information Services; Erectile Dysfunction; Formularies as Topic; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

To critically review the literature on vardenafil in the treatment of erectile dysfunction while integrating the clinical findings with the personal experience of the authors.. Analysis of published full-length papers that were identified through Medline search from January 2000 through May 2004. Abstracts published in peer-reviewed journals from the same period were also considered.. Efficacy, tolerability and safety, as reported in the peer-reviewed literature compares well with the authors' personal experience. Authors' personal observations include discussions on potency, selectivity, selection of initial dose, counselling for patients characteristically considered difficult-to-treat (diabetes, prostatectomy, depression), including the determination of the maximal efficacious dose and the possible role of daily dosing, optimisation of the use of vardenafil according to its pharmacokinetic and pharmacodynamic profiles (onset and reliability), and management of ED patients with or at risk for cardiovascular disease.. Extensive experience with vardenafil as reported in peer reviewed literature confirms the important role of vardenafil in the management of patients with ED. The development of each physician's own experience with vardenafil is key to optimise overall satisfaction of this therapy by the patient and his partner.

Topics: Clinical Competence; Erectile Dysfunction; Humans; Imidazoles; Male; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Safety; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Diabetes Complications; Diabetic Neuropathies; Diagnosis, Differential; Erectile Dysfunction; Humans; Imidazoles; Male; Nitric Oxide; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

The field of erectile dysfunction (ED) has been revolutionised over the last two decades. Several treatment options are available today, most of which are associated with high efficacy rates and favourable safety profiles. A MEDLINE search was undertaken in order to evaluate all currently available data on treatment modalities for ED. Phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil, vardenafil) are currently the first-choice of most physicians and patients for the treatment of ED. PDE5 inhibitors have differences in their pharmacological profiles, the most obvious being the long duration of action of tadalafil, but there are no data supporting superiority for any one of them in terms of efficacy or safety. Sublingual apomorphine has limited efficacy compared with the PDE5 inhibitors, and its use is limited to patients with mild ED. Treatment failures with oral drugs may be due to medication, clinician and patient issues. The physician needs to address all of these issues in order to identify true treatment failures. Patients who are truly unresponsive to oral drugs may be offered other treatment options.Intracavernous injections of alprostadil alone, or in combination with other vasoactive agents (papaverine and phentolamine), remain an excellent treatment option, with proven efficacy and safety over time. Topical pharmacotherapy is appealing in nature, but currently available formulations have limited efficacy. Vacuum constriction devices may be offered mainly to elderly patients with occasional intercourse attempts, as younger patients show limited preference because of the unnatural erection that is associated with this treatment modality. Penile prostheses are generally the last treatment option offered, because of invasiveness, cost and non-reversibility; however, they are associated with high satisfaction rates in properly selected patients. All treatment options are associated with particular strengths and weaknesses. A patient-centred approach based on patient needs and expectations is necessary for the management of ED. The clinician must educate the patient and provide a supportive environment for shared decision making. The management strategy must be supplemented by careful follow-up in order to identify changes in patient health and relationship/emotional status that may necessitate treatment optimisation.

Topics: Administration, Oral; Alprostadil; Apomorphine; Carbolines; Constriction; Contraindications; Dopamine Agonists; Drug Combinations; Enzyme Inhibitors; Erectile Dysfunction; Humans; Imidazoles; Male; Papaverine; Patient Satisfaction; Penile Prosthesis; Penis; Phentolamine; Phosphodiesterase Inhibitors; Piperazines; Purines; Regional Blood Flow; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Failure; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Differences in the clinical pharmacology of the 3 currently available oral phosphodiesterase-5 (PDE5) inhibitors, sildenafil, vardenafil, and tadalafil, are largely determined by their clinical pharmacokinetics as well as their PDE inhibitory activity profile. This review comparatively discusses the major characteristics of the pharmacokinetic profile of all 3 PDE5 inhibitors, including bioavailability and rate of absorption, Biopharmaceutical Classification System categorization, elimination mechanisms, and metabolic profile including active metabolites, as well as the drug-drug interaction potential and modification of pharmacokinetic properties under selected physiologic and pathophysiologic conditions. The review is aimed at providing comparative clinical pharmacology data to allow for scientifically rational, evidence-based prescribing and dosing decisions regarding the clinical use of these medications for the treatment of erectile dysfunction.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Biological Availability; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Cytochrome P-450 CYP3A; Drug Interactions; Erectile Dysfunction; Humans; Imidazoles; Male; Metabolic Clearance Rate; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Understanding patient preferences can be important in ensuring full benefit is derived from treatment for erectile dysfunction (ED). They seem to be important in determining whether patients continue treatment in the medium and long term. In clinical practice, discontinuation rates beyond a year are relatively high. Factors such as spontaneity, "naturalness", and onset and duration of action may all influence preference. This article discusses a number of studies looking into patient preferences for a particular class of treatment method over another, and also for individual treatments within classes. In general, patients appear to prefer oral treatments to others such as penile implant surgery, vacuum-pump therapy, apomorphine, and intracavernosal injection. In some studies, men have also shown preferences for particular oral phosphodiesterase-5 (PDE5) inhibitors over others. Providing patients with full information on the pros and cons of treatment options can help ensure patients are treated with a therapy that fits more closely with their wishes, and ensure continuation of treatment for optimal efficacy.

Topics: Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Patient Education as Topic; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Purines; Safety; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

The rate of erectile dysfunction after radical retropubic prostatectomy is from 10% to 100%. The prevalence of erectile dysfunction after nerve-sparing radical prostatectomy is more than one third. In the patients who had undergone bilateral NS, 72% responded to sildenafil, 71.7% and 59.7% responded to 20 mg and 10 mg of vardenafil respectively. For all randomized patients who received tadalafil, the mean percentage of successful penetration attempts was 54% and the mean percentage of successful intercourse attempts was 41%. For the subgroup with evidence of postoperative tumescence these values were 69% and 52%, respectively. No head-to-head trials have been performed with sildenafil, vardenafil and tadalafil in treatment of erectile dysfunction after radical prostatectomy.

Topics: Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Prostatectomy; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) affects the sexual lives of millions of men. The first-line oral pharmacotherapy for most ED patients is phosphodiesterase type-5 (PDE-5) inhibitors, of which three are available. Sildenafil is the most widely prescribed oral agent for ED and has a very satisfactory efficacy-safety profile in all patient categories. Tadalafil and vardenafil were introduced in the European Union and in the United States in 2003 and 2004, respectively. The three PDE-5 inhibitors share many pharmacological and clinical characteristics, and each has unique features. This review, which is based on the contemporary literature on PDE-5 inhibitors, describes the chemical, pharmacological, and clinical features of sildenafil, vardenafil, and tadalafil. The first section reviews the pathophysiology of penile erection and PDE-5 inhibitor pharmacology. The second section summarizes data regarding efficacy and safety of the three drugs in treating ED in the general population as well as in selected patient categories.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Phosphodiesterase-5 (PDE-5) inhibitors are a well-established, first-line therapy for erectile dysfunction (ED). Extensive clinical trials and clinical experience established the highly significant efficacy and the safety of this class of drugs in the treatment of ED.Furthermore, the efficacy of PDE-5 inhibitors has been established in men with ED with a broad range of etiologies and comorbidities. The future of PDE-5 inhibitors includes the expansion of indications such as the treatment of pulmonary hypertension and the potential of treatment of symptomatic BPH.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Forecasting; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

The recent reports of non-arteritic anterior ischemic optic neuropathy (NAION) occurring shortly after ingestion of erectile dysfunction agents have raised the question of whether these agents have a cause-and-effect relationship to NAION. The nature of optic nerve head blood flow and the various factors that influence it, the systemic vascular effects of these agents, and the clinical features of NAION lead me to believe that these agents are contributory factors. Patients with the appropriate risk factors should, therefore, be warned of this possibility and advised to refrain from using these agents.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Optic Disk; Optic Neuropathy, Ischemic; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Erectile function is determined by tight regulation of relaxation or contraction of corpus cavernosal smooth muscle, which is the result of a long and complex chain of molecular events. Control of erectile function resides in signaling pathways of the central and peripheral nervous system, as well as intracellular events in the penile smooth muscle. Vascular events resulting in erection have long been understood, and the role of the signaling pathways of the central and peripheral nervous systems in erectile function and dysfunction has become increasingly clear over the last decade. This knowledge has led to the development and current availability of effective oral treatments for erectile dysfunction, the selective phosphodiesterase type 5 (PDE5) inhibitors-sildenafil, vardenafil and tadalafil. In the past few years we have seen an elucidation of the molecular events involved in erectile function and dysfunction and the detailed mechanisms of action by which the specific PDE5 inhibitors work. A review of those mechanisms helps to explain the success of the currently available PDE5 inhibitors and the differences between them and suggests new approaches for developing potential future novel therapies or refinements to existing structures that may improve their efficacy, selectivity and safety profiles.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Interactions; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Currently, 3 phosphodiesterase 5 (PDE5) inhibitor agents are available worldwide for the treatment of erectile dysfunction (ED): sildenafil, vardenafil, and tadalafil. Each of these agents is effective across a broad range of etiologies, including vasculogenic ED in men. Because PDE5 enzyme is found within the vascular smooth muscle cells in the walls of systemic arteries and veins, PDE5 inhibitors are mild vasodilators associated with small (and in general, clinically insignificant) decreases in blood pressure. However, because of the synergistic decrease in blood pressure (both systolic and diastolic) in the presence of organic nitrates, these 3 agents are contraindicated in patients receiving organic nitrates. The duration of interaction between a PDE5 inhibitor and nitrate administration depends on the specific drug being studied. The interaction between sildenafil or vardenafil and nitroglycerin is no longer observed by 24 hours. A preliminary study with sildenafil and sublingual nitroglycerin suggested the interaction is no longer observable by 4 hours. The interaction between tadalafil and nitroglycerin has dissipated by 48 hours after tadalafil administration. This is consistent with the longer elimination half-life of the drug. When PDE5 inhibitors are administered to patients with hypertension who are taking most antihypertensive agents (eg, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium antagonists, diuretics), there are usually small additive decreases in blood pressure without a significant increase of adverse events. Some patients develop orthostatic hypotension when PDE5 inhibitors are used in conjunction with an alpha-blocker (typically for hypertension or for urologic conditions, such as benign prostatic hypertrophy). Precautions are necessary for all 3 of the PDE5 inhibitors regarding this potential interaction. Some studies suggest that the interaction is less relevant clinically if the patient has been undergoing long-term alpha-blocker therapy. Several analyses have suggested that PDE5 inhibitors do not increase myocardial infarction rates or death rates compared with placebo controls or expected rates from age-matched populations. In contrast, recent studies have shown that PDE5 inhibitors may have therapeutic potential for a host of cardiovascular diseases. In general, these agents, when used appropriately, are highly safe and effective.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adrenergic alpha-Antagonists; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Interactions; Erectile Dysfunction; Humans; Imidazoles; Male; Nitroglycerin; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Phosphodiesterase type 5 (PDE5) inhibitors have revolutionized the treatment of erectile dysfunction (ED). Those safe and effective agents were originally developed for their cardiovascular effects and were incidentally found to enhance erections. Since the introduction of the first PDE5 inhibitor, sildenafil, in 1998, there has been concern about the effects of these agents on the heart and their safety in patients with cardiovascular disease. The concerns focused on the effects on blood pressure and heart rate, cardiac electrophysiology, and cardiovascular adverse events in clinical trials. Since there are currently three PDE5 inhibitors, attention has been given to class effects as well as unique individual safety and adverse events. Since these drugs are mild vasodilators, all three have blood pressure-lowering effects. These effects are usually mild and produce few symptoms. When combined with the nitric oxide donor nitroglycerine, however, blood pressure drops may be profound and life threatening. All three agents are contraindicated with nitrates. Cardiac electrophysiology effects, especially as manifested by changes in the QT interval, have been studied. None of the three agents are dangerously associated with QTc prolongation, although vardenafil has a warning for patients at risk for QTc prolongation. In evaluating cardiovascular adverse events in clinical trials, no signal to danger can be convincingly cited. Indeed, with the vasodilator effects of these drugs, many studies point to the improved exercise tolerance and coronary dilation in patients taking PDE5 inhibitors. PDE5 inhibitors are effective in treating ED, and their safety profile is excellent. There do not appear to be significant cardiovascular safety issues in the man with satisfactory cardiac and performance status.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Blood Pressure; Carbolines; Clinical Trials as Topic; Coronary Artery Disease; Cyclic Nucleotide Phosphodiesterases, Type 5; Electrophysiology; Erectile Dysfunction; Heart Rate; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men. At present, first-line oral pharmacotherapy for most patients with ED is a phosphodiesterase type 5 (PDE-5) inhibitor, of which three are currently available worldwide. Sildenafil (Viagra, Pfizer) has a very satisfactory efficacy-safety profile in all patient categories. The first PDE-5 inhibitor to reach the market, it is now the most widely prescribed oral agent for ED. Tadalafil (Cialis, Lilly ICOS) and vardenafil (Levitra, Bayer/GlaxoSmithKline) were introduced to the European Union and the US in 2003 and 2004, respectively. These three PDE-5 inhibitors share many characteristics, but each has unique features. This review describes the chemical, pharmacologic and clinical features of sildenafil, vardenafil and tadalafil as oral first-line treatments for ED. First, we describe the physiology of penile erection and PDE-5 inhibitor pharmacology, including chemistry, PDE selectivity, pharmacokinetics, and possible drug interactions. We then summarize data on the efficacy and safety profiles of the three PDE-5 inhibitors for the treatment of ED in the general population, in patients with diabetes mellitus and in men that have undergone bilateral nerve-sparing retropubic radical prostatectomy.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Administration, Oral; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) is a widespread, age-related medical condition that affects > 50% of men aged 40 - 70 years. Pharmacotherapy with orally available phosphodiesterase 5 (PDE5) inhibitors offers a convenient and simple approach to treatment. Results of numerous clinical trials have demonstrated significant efficacy in restoring the ability to achieve and sustain an erection, and adverse side effects are generally mild-to-moderate in severity. Vardenafil is a highly selective, potent PDE5 inhibitor developed for the treatment of ED. The potency and selectivity of vardenafil for PDE5 and other PDE isoforms have been evaluated in vitro and in vivo and compared with other compounds in the class. This review will discuss the findings of biochemical, in vitro and in vivo experiments that indicate the superior potency and high selectivity of vardenafil.

Topics: Animals; Clinical Trials as Topic; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To review the pharmacology, pharmacokinetics, clinical trial data, and adverse effects of vardenafil in the treatment of erectile dysfunction (ED).. Literature searches were performed using the MEDLINE database (referenced citations through December 2002), and the references of all identified articles were scanned for additional publications of interest. Unpublished information provided by the manufacturer and proceedings of professional meetings were also evaluated.. All available studies were utilized to obtain information regarding pharmacology. Only human studies were used to gather pharmacokinetic, drug interaction, efficacy, and safety data.. Vardenafil is a potent and selective inhibitor of the phosphodiesterase 5 (PDE5) enzyme that has been shown to improve erectile function in several populations of men with ED. Vardenafil has a rapid onset of action, is hepatically metabolized, and has a half-life of 4-6 hours. Clinical trials in otherwise healthy men with ED, men with ED and diabetes, and men with ED and a history of prostatectomy have demonstrated vardenafil's efficacy. Adverse effects appear to be relatively mild in intensity and dose dependent, with 22-61% of subjects reporting adverse effects.. Vardenafil is a safe and effective oral agent for the treatment of ED. Its greater potency and PDE5 selectivity compared with sildenafil appear to confer a lower risk of vision-related adverse effects, but other clinical consequences of these differences are currently unclear.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Sulfones; Time Factors; Triazines; Vardenafil Dihydrochloride

Vardenafil (Levitra) is a potent and highly selective oral phosphodiesterase type 5 (PDE5) inhibitor. Vardenafil improved erectile function in men with mild to severe erectile dysfunction (ED) of varying aetiology in two randomised, double-blind, multicentre, fixed-dose studies of 12 or 26 weeks' duration. Men receiving vardenafil 10 or 20mg had significantly greater improvements in International Index of Erectile Function (IIEF) questionnaire erectile function domain scores than placebo recipients. Moreover, improvements in penetration and maintenance of erection (assessed using IIEF or Sexual Encounter Profile [SEP] questions) were significantly greater with vardenafil 5-20mg than with placebo. Improvements in IIEF intercourse satisfaction and orgasmic function domain scores were significantly greater with vardenafil 10 or 20mg than with placebo and the proportion of patients with a positive response to a Global Assessment Question (GAQ) concerning improvement in erections after 12 or 26 weeks' therapy was significantly higher with vardenafil 5-20mg than with placebo. Vardenafil improved erectile function in men with ED associated with diabetes mellitus or ED following unilateral or bilateral nerve-sparing radical retropubic prostatectomy in two randomised, double-blind, multicentre, fixed-dose, 3-month studies. In both studies, improvements from baseline in the erectile function domain score of the IIEF and in positive responses to SEP questions were significantly greater with vardenafil 10 or 20mg than with placebo. In addition, a significantly higher proportion of vardenafil 10 or 20mg recipients than placebo recipients had positive GAQ responses. Vardenafil was generally well tolerated in men with ED; treatment-emergent adverse events were of mild to moderate intensity and transient in nature. The most commonly reported adverse events (typical of those seen with PDE5 inhibitors) in vardenafil 5-20mg recipients included headache, flushing, rhinitis, dyspepsia and sinusitis. There were no reports of abnormal colour vision in men with ED taking vardenafil at clinically recommended doses (5-20mg).. Vardenafil is a potent and highly selective oral PDE5 inhibitor. It is effective and generally well tolerated in men with mild to severe ED of varying aetiology, as well as in men with ED associated with diabetes mellitus or ED after radical prostatectomy. Vardenafil should be considered a first-line treatment option in men with ED who are suitable candidates for oral PDE5 inhibitor therapy.

Topics: Administration, Oral; Biological Availability; Diabetes Complications; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Piperazines; Randomized Controlled Trials as Topic; Severity of Illness Index; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction is a common, age-dependent functional disturbance of men associated to various comorbidities. Interdisciplinary cooperation with neurologists in cases of a suspected neurological aetiology and with psychiatrists in cases with normal organic diagnostic findings is necessary. Hormone replacement and psychotherapy can cure certain patients. Oral pharmacotherapy is the most effective therapy for erectile dysfunction with the highest patient preference. Oral PDE-5-inhibitors (sildenafil, tadalafil, vardenafil) are superior in effectiveness to centrally acting drugs (apomorphin, yohimbine). Local pharmacotherapy (MUSE, ICI) is a second line therapy in cases of failure or contraindications for oral pharmacotherapy. Vacuum therapy and operative procedures (penile implants) complete the therapeutic options of erectile dysfunction.

Topics: Erectile Dysfunction; Humans; Imidazoles; Male; Patient Care Management; Penile Prosthesis; Phosphodiesterase Inhibitors; Piperazines; Psychotherapy; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Erectile dysfunction (ED) is an inability to attain or maintain an erection sufficient for satisfactory sexual intercourse. It is an undertreated and underdiagnosed condition that can be due to vasculogenic, neurogenic, hormonal and psychogenic factors. Effective treatment of ED should restore quality of life and allow patients to return to the sex life they had before. Current therapeutic options include non-pharmacological treatments, locally administered drugs and oral therapies. The oral phosphodiesterase-5 (PDE5) inhibitors are considered first-line treatments of ED and have revolutionized ED management in the last five years. Three PDE5 inhibitors are currently available, sildenafil, vardenafil and tadalafil. They are all effective with similar efficacy and good safety profiles. However, tadalafil has the added benefit of a broad window opportunity offering patients more freedom to choose when to initiate sexual activity.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Administration, Oral; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Molecular Structure; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vacuum; Vardenafil Dihydrochloride; Vasodilator Agents

Topics: Adrenergic alpha-Antagonists; Androgens; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phytotherapy; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents; Yohimbine

No head-to-head studies have been conducted with the phosphodiesterase type 5 (PDE5) inhibitors to date. Results of noncomparative studies, however, suggest that tadalafil and vardenafil hydrochloride are at least as effective as sildenafil citrate in improving erections and increasing the number of successful intercourse attempts in men with erectile dysfunction (ED) at all levels of severity. By facilitating a sexual response, PDE5 inhibitors lend naturalness to sexual activity and may permit couples to return to their previous sexual lifestyle. By providing a broader window of opportunity, a longer-acting PDE5 inhibitor such as tadalafil adds to the variety of options currently available in managing ED with PDE5 inhibitors. This option offers increased flexibility by minimizing the need to plan sexual activity; allowing more time for intimacy or romance before sexual intercourse; and reducing the pressure on the patient to perform.

Topics: Adult; Drug Evaluation; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Participation; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Clinical evidence in men with erectile dysfunction (ED) shows that the phosphodiesterase type 5 (PDE5) inhibitors sildenafil citrate, tadalafil, and vardenafil hydrochloride have favorable safety and efficacy profiles. However, as mild vasodilators, the PDE5 inhibitors are also associated with hemodynamic effects that may be clinically significant, especially when treating men with ED who have comorbid cardiovascular disease. Hemodynamic studies have shown that therapeutic dosages of the PDE5 inhibitors produce only mild and transient changes in mean systolic and diastolic blood pressure and heart rate in healthy men as well as those with ischemic heart disease or chronic stable angina. Overall, PDE5 inhibitors are safe and effective in most patient populations, including men with ischemic cardiovascular disease or those receiving anti-hypertensive agents, and men with diabetes or those who have undergone nerve-sparing retropubic radical prostatectomy. With the entry of three novel PDE5 inhibitors into the therapeutic armamentarium for ED, differentiating properties of the new agents may confer clinical benefits that physicians as well as patients and their partners should consider when selecting a PDE5 inhibitor.

Topics: Antihypertensive Agents; Cardiovascular Diseases; Diabetes Complications; Drug Interactions; Erectile Dysfunction; Humans; Imidazoles; Male; Nitrates; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Orally administered phosphodiesterase type 5 (PDE5) inhibitors have become the first-line treatment option for erectile dysfunction (ED). Vardenafil is a potent and highly selective PDE5 inhibitor developed as an oral therapy for ED. Two pivotal, randomised, double-blind, multi-centre studies have evaluated the use of vardenafil in men with ED. Vardenafil improved the rate of achieving and maintaining an erection during sexual intercourse. Improvement was also noted in other aspects of sexual function, including confidence, orgasmic function and overall satisfaction. Vardenafil produces clinically and statistically significant improvements in erectile function regardless of age, baseline severity and aetiology and is efficacious for the treatment of ED in diabetic and postradical prostatectomy patients. Vardenafil has a rapid onset of action, in which erections sufficiently rigid for eventual intercourse completion can be achieved as early as 16 min after ingestion. Vardenafil 20 mg has sustained long-term efficacy by providing up to 92% of patients with improved erections during > 2 years of treatment. Vardenafil is well-tolerated, with an adverse event profile typical of this class of PDE5 inhibitors. The most common adverse events were headache, flushing, rhinitis and dyspepsia, which were mild-to-moderate in severity and they generally attenuated with continued use. Vardenafil may be associated with transient reductions in blood pressure and commensurate increases in heart rate, with the overall incidence of cardiovascular-related adverse events similar to that of placebo. Although claims can be made about potential features of benefit for each of the currently marketed PDE5 inhibitors, there are at present, no non-pharmaceutical company sponsored, peer-reviewed, head-to-head trials that have been published.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Randomized Controlled Trials as Topic; Sulfones; Triazines; Vardenafil Dihydrochloride

Dramatic advances in the management of erectile dysfunction have occurred over the past decade. Oral therapy with vasoactive agents has emerged as first-line treatment and has transformed both the manner in which the public views erectile dysfunction and the way health care providers deliver care. Whereas an extensive investigation was previously common in the management of erectile dysfunction, recent treatment guidelines promote a more minimalist, goal-oriented approach. In this article, we review the physiology of erection, and the pathophysiology, diagnosis and clinical management of erectile dysfunction. We also present the existing evidence for the efficacy of 3 phosphodiesterase inhibitors, the most widely used class of agents for erectile dysfunction.

Topics: Erectile Dysfunction; Humans; Imidazoles; Male; Penile Erection; Phosphodiesterase Inhibitors; Physical Examination; Piperazines; Purines; Sildenafil Citrate; Sulfones; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men worldwide. Many drugs are now available for the treatment of ED, with oral pharmacotherapy representing the first-line option for most patients. Sildenafil citrate, an inhibitor of the enzyme phosphodiesterase type 5 (PDE5), is the most widely prescribed oral agent and has a very satisfactory efficacy-safety profile in all patient categories. Tadalafil (Cialis; Eli Lilly & Co., ICOS) and vardenafil (Levitra; Bayer Pharmaceuticals, GlaxoSmithKline) are new PDE5 inhibitors that have recently been approved worldwide. Both have been associated with significant positive efficacy-safety profiles. Apomorphine sublingual is a dopamine D1 and D2 receptor agonist, which has been approved for marketing in Europe. It is best selected for treating patients with mild-to-moderate ED, but it is seldom used in clinical practice due to its limited efficacy and side effects, particularly nausea. Patients who do not respond to oral pharmacotherapy or who are unable to use it are appropriate candidates for intracavernosal and intraurethral therapy. The efficacy of second-line treatment is high, but the attrition rate remains significant. For the purpose of this review, clinical and pharmacological analysis focuses on the recent advances in the field of oral therapy, including PDE5 inhibitors and sublingual apomorphine.

Topics: Administration, Oral; Administration, Sublingual; Adult; Aged; Apomorphine; Carbolines; Comorbidity; Cross-Over Studies; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Dopamine Agonists; Double-Blind Method; Drug Interactions; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Multicenter Studies as Topic; Nitric Oxide; Phosphodiesterase Inhibitors; Piperazines; Purines; Randomized Controlled Trials as Topic; Second Messenger Systems; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Trials of the efficacy and safety of vardenafil in the treatment of male erectile dysfunction (ED) were meta-analysed. All available databases were searched (January 1, 2001-November 30, 2003). Trials were eligible if they included men with ED, compared vardenafil with placebo, were randomized, were at least of 12 weeks duration, and assessed clinically relevant outcomes. Two reviewers independently evaluated study quality and extracted data in a standardized fashion. Nine trials (6809 men) met the inclusion criteria. In results pooled from seven fixed-dose trials, vardenafil increases the Erectile Function domain of the International Index of Erectile Function questionnaire by 6.18 units (weighted mean difference (WMD)). Vardenafil also increases the percentage of erections firm enough to allow vaginal penetration (WMD: 26) and the percentage of sexual attempts that were successful per participant (WMD: 29.8). The percentage of men agreeing with the statement that 'the treatment they have been taking over the past 4 weeks improved their erections', is also in favour of vardenafil (relative risk (RR): 3). These efficacy variables appeared greater at higher doses, although there are no significant differences between 10 and 20 mg dose. The same results were extracted for the two flexible 'as needed' dosing trials. Discontinuations are greater at the vardenafil groups compared to placebo (RR: 2.25). Specific adverse events with vardenafil included flushing, dyspepsia, headache, and rhinitis. Vardenafil was not significantly associated with serious cardiovascular events or death. Vardenafil, in all treatment regimens, shows to possess superior efficacy to placebo in the treatment of patients with erectile dysfunction. More data is needed on patients' subgroups.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; MEDLINE; Penile Erection; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Placebos; Randomized Controlled Trials as Topic; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

In 1998, we concluded that sildenafil (Viagra--fizer Ltd), a selective phosphodiesterase type 5 inhibitor, appeared to offer advantages over other medical approaches for erectile dysfunction in terms of ease of administration and cost. Oral drug treatment is now widely advocated as first-line therapy for erectile dysfunction, except where the cause is clearly psychological. In the past 4 years, three more oral preparations have been licensed in the UK for the treatment of men with erectile dysfunction. A sublingual preparation of the dopaminergic agonist apomorphine (Uprima--Abbott Laboratories Ltd) is the first centrally acting drug to be licensed. Tadalafil (Cialis--Eli-Lilly) and vardenafil (Levitra--Bayer PLC) are phosphodiesterase type 5 inhibitors. Here we review the place of these preparations for men with erectile dysfunction.

Topics: Apomorphine; Carbolines; Dopamine Agonists; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Randomized Controlled Trials as Topic; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Vardenafil is a new phosphodiesterase type-5 inhibitor for the treatment of men with erectile dysfunction (ED). It was licensed in Europe in spring 2003 and in the USA in late 2003. It is a potent and selective inhibitor of the enzyme phosphodiesterase type 5, and in the presence of an erectile stimulus potentiates the intracellular actions of cyclic guanylate monophosphate. Several large, placebo-controlled trials have demonstrated efficacy both in the broad population of men with ED and in men with more difficult to treat ED. It is well tolerated with a side effect profile typical of this class of drugs. It has a rapid onset of action and has demonstrable efficacy for men using the medication for up to 2 years.

Topics: Clinical Trials as Topic; Drug Interactions; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adrenergic alpha-Antagonists; Arteriosclerosis; Blood Pressure; Carbolines; Contraindications; Coronary Disease; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Interactions; Endothelium, Vascular; Erectile Dysfunction; Heart Rate; Humans; Hypotension; Imidazoles; Isosorbide Dinitrate; Male; Molecular Structure; Myocardial Infarction; Nitric Oxide Donors; Nitroglycerin; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilation; Vasodilator Agents

The purpose of this review is to examine the biologic, pharmacologic, and clinical differences between the three currently approved phosphodiesterase-5 inhibitors to help the clinician make an educated choice about which medication may be best for any individual patient.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Topics: Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Patient Selection; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

With the success of Phosphodiesterase (PDE) type 5 inhibitors (i.e., sildenafil, tadalafil, vardenafil) in the treatment of erectile dysfunction (ED), PDEs are considered attractive targets for drug intervention in the urogenital tract.. To review the role of PDEs, which exist as a superfamily of enzymes comprising 11 distinct families, in the urogenital system, focusing on anatomical locations, functions and dysfunctions, potential disorders that could be treated, and any promising new selective PDE inhibitors under development.. Included are (i) abstracts from 2001, 2002, and 2003; (ii) a MEDLINE search from 1996 through December 2003; and (iii) a pipeline search for therapeutics in development. Data from animal experiments are presented when there is a paucity of human data, but with the caveat that the distribution of PDE isozymes in a specific tissue can vary between species.. PDE mRNA and protein have been localized throughout the normal human urogenital tract. Double-blind, placebo-controlled studies suggest possible new clinical roles for sildenafil, including prophylaxis to preserve penile smooth muscle and erectile function after radical prostatectomy, and treatment of ejaculatory delay secondary to serotonergic reuptake inhibitor antidepressant therapy. Open-label studies suggest a potential clinical role for: vinpocetine (a PDE1 inhibitor) in the treatment of incontinence and low-compliance bladder; and sildenafil in the treatment of premature ejaculation, prostate-related lower urinary tract symptoms, and in women who have had unsuccessful in vitro fertilization. Several new orally administered PDE5 inhibitors are in early clinical development for the treatment of ED. Potential indications for PDE inhibitors that are suggested by preclinical data include Peyronie's disease, ureteral colic, male and female birth control, and prevention of preterm labor.. Drug selectivity and differential PDE tissue distribution allow for potential targeted intervention for numerous disorders related to the urogenital tract.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Ejaculation; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; RNA, Messenger; Sildenafil Citrate; Sulfones; Tadalafil; Time Factors; Triazines; Urogenital System; Vardenafil Dihydrochloride

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men worldwide. Many drugs are now available for treating ED; oral pharmacotherapy represents the first-line option for most patients with ED. Sildenafil, an inhibitor of the enzyme phosphodiesterase type 5, is currently the most widely prescribed oral agent and has a very satisfactory efficacy-safety profile in all patient categories. Apomorphine SL is a dopamine D1- and D2-receptor agonist which has recently been approved for marketing in Europe. It is best selected for treating patients with mild to moderate ED. Vardenafil and tadalafil are new phosphodiesterase type 5 inhibitors which are expected to be approved this year. Both of them have significant positive efficacy-safety profiles. Patients who do not respond to oral pharmacotherapy or who cannot use it are good candidates for intracavernosal and intraurethral therapy. Alprostadil is the most widely used drug, both for injection therapy and for the intraurethral route. The efficacy of second-line treatment is high but the attrition rate remains significant.

Topics: Administration, Oral; Adrenergic alpha-Antagonists; Alprostadil; Apomorphine; Carbolines; Drug Combinations; Erectile Dysfunction; Humans; Imidazoles; Injections; Male; Papaverine; Phentolamine; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

The phosphodiesterase enzymes, of at least 11 types, are ubiquitous throughout the body, and perform a variety of functions. Phosphodiesterase type 5 (PDE5) is the predominant enzyme in the corpus cavernosum, and plays a crucial role in penile erection. Inhibitors of PDE5 are the most effective oral agents in the treatment of erectile dysfunction. Sildenafil, tadalafil, and vardenafil are all potent inhibitors of PDE5 and show the same mechanism of action, although they have some pharmacological differences that may translate into varying clinical effects.

Topics: Administration, Oral; Aged; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Prognosis; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Topics: Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Patient Compliance; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Inhibitors of phosphodiesterase type 5 are playing a large role in the revolution in the treatment of sexual dysfunction that has taken place in recent years. The revolution was launched in 1998 with the introduction of a phosphodiesterase type 5 inhibitor, sildenafil, which opened up new avenues of investigation and greater recognition of the prevalence and various characteristics of these conditions. As more treatments with this and other mechanisms of action reach advanced stages of development and international markets, clinicians and patients alike are gaining confidence in the idea that sexual dysfunction can be successfully treated, and this, in turn inspires further research. While the efficacy of sildenafil has been striking, the drug is not effective and agreeable for all patients. Researchers have naturally sought to exploit this drug's mechanism of action in the hope that other agents can be found that are more selective, potent and tolerable. The etiology of sexual dysfunction is variable, as are its manifestations and the requirements patients have for therapy, and it is therefore likely that numerous treatments will be used to enhance sexual satisfaction in this population. Vardenafil, a new phosphodiesterase type 5 inhibitor, is an agent which has shown promise at each stage of development. The drug is currently in the third phase of clinical testing for the treatment of erectile dysfunction.

Topics: Animals; Erectile Dysfunction; Humans; Imidazoles; Male; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

Efficacy is a deciding factor in the selection of a therapy, also by erectile dysfunction. With PDE-5 inhibitors, efficacy can only be determined using subjective information from the patient. Various methods have been developed to quantify this information. If one attempts to compare Sildenafil, Tadalafil and Vardenafil using currently available data, it is necessary to bear in mind that groups of patients with differing severity of erectile dysfunction and various placebo response rates were examined. In addition, patients for whom Sildenafil did not work were excluded from important studies with Tadalafil and Vardenafil. Taking into consideration these factors, the new drugs show no advantages over Sildenafil. Moreover, detailed data for the counselling of certain patient groups is at present only available for Sildenafil, and there is, in addition, a high degree of patient satisfaction with this drug. The "gold standard" for the therapy of erectile dysfunction is Sildenafil and the effectiveness of all new drugs must be compared to it.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Clinical Trials as Topic; Cyclic Nucleotide Phosphodiesterases, Type 5; Dose-Response Relationship, Drug; Erectile Dysfunction; Humans; Imidazoles; Male; Multicenter Studies as Topic; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

The development of diagnostical and therapeutical methods of erectile dysfunction opened new possibilities for patients. In our time, andrologists are capable of treating most patients. The ones who cannot be helped are unable to lead sexual life due to physical reasons. The application of hormone examinations, color Doppler and Rigiscan exams help at establishing diagnoses. In the therapy, modern peroral pharmacotherapy is dominant, mainly phosphodiesterase inhibitors and central peroral pharmacon are applied. The means of getting the vasoactive drugs into the body have been extended (subcutan, transdermal, and drugs absorbable through mucosa). Psychotherapy is indispensable at some patients. The surgical solution (mainly prosthesis implantation) can be regarded critically, yet their presence among therapies is necessary. According to authors' opinion, the qualitative development of vasoactive drugs (efficacy extension and side-effect reduction) that can be simply and conveniently applied in the future.

Topics: Administration, Oral; Adrenergic alpha-Antagonists; Alprostadil; Apomorphine; Dopamine Agonists; Erectile Dysfunction; Humans; Imidazoles; Impotence, Vasculogenic; Injections; Male; Nitric Oxide; Papaverine; Phosphodiesterase Inhibitors; Piperazines; Psychotherapy; Purines; Sildenafil Citrate; Sulfones; Triazines; Vacuum; Vardenafil Dihydrochloride; Vasodilator Agents

Risk factors for erectile dysfunction (ED) (hypertension, diabetes, smoking, lipid abnormality) are also risk factors for coronary artery disease. However, most cardiologists do not routinely ask about ED and patients often are reluctant or embarrassed to discuss it. We determined how common ED was in a group of patients with chronic stable coronary artery disease.. We administered the validated Sexual Health Inventory for Men (SHIM) 5-item questionnaire, based on the International Index of Erectile Function questionnaire, to 76 men with chronic stable coronary artery disease during routine outpatient cardiology visits. Most of these men had not previously discussed ED with their cardiologist.. The mean patient age was 64 years (range 40 to 82). The questionnaire took about 5 minutes to complete. Of the patients 47% were on beta blockers, 92% statins, 28% diuretics. SHIM score was 21 or less in 53 men (70%), which is indicative of ED. Of the patients 75% had some difficulty achieving erections (question 2) and 67% had some difficulty maintaining an erection after penetration (question 3). The questionnaire reflected successful sildenafil treatment in 4 patients (SHIM scores 23 to 25). If these 4 men are included as having had ED then 57 of 76 (75%) had ED or recent history of ED.. ED is extremely common in men with chronic coronary artery disease (affecting approximately 75%) yet most cardiologists do not ask about it. The SHIM is a useful, quick and inexpensive tool for discussion and diagnosis of ED in this population. Although it is well established that cardiovascular risk factors are associated with erectile dysfunction, once it is present there is mixed information on whether treating the risk factors will treat the ED. Problems appear to be that lifestyle modification in midlife may simply be too late to effect a change, and some antihypertensive and lipid lowering drugs may actually exacerbate ED. Oral therapy for ED, namely the PDE5 inhibitors, is effective and safe in most cardiac and hypertensive patients. Organic nitrates such as nitroglycerin remain a contraindication to the concomitant use of these drugs. Guidelines for treatment of ED in the cardiac patient issued by the American College of Cardiology/American Heart Association and Princeton Guidelines may be useful in the approach to the cardiac patient with ED.

Topics: Comorbidity; Coronary Disease; Diabetic Angiopathies; Erectile Dysfunction; Heart Diseases; Humans; Hypertension; Imidazoles; Life Style; Male; Penile Erection; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Smoking; Sulfones; Triazines; Vardenafil Dihydrochloride

Phosphodiesterase 5 inhibitors are preferred by most men for the oral treatment of erectile dysfunction. In many guidelines, this therapy is recommended as first-line therapy because of convenience, high efficacy, and low rates of side-effects. Sildenafil was the first drug for the treatment of erectile dysfunction, introduced in 1998. There are now two new phosphodiesterase 5 inhibitors, vardenafil and tadalafil, for which approval was recently given in the European Union and is expected this year in the United States.. Sildenafil has proved to be a very effective medicinal product. According to initial studies, vardenafil and tadalafil have demonstrated efficacy comparable to that of sildenafil. However, fewer data are available evaluating the adverse effects of vardenafil and tadalafil, particularly on their long-term use and their use in high-risk groups. Interestingly, vardenafil and tadalafil have a higher potency than sildenafil. Moreover, the long life of tadalafil has been associated with an erectogenic potential of the drug lasting for more than 24 h. The advantage of this is the possibility of a patient engaging in sexual activity more than once after a single administration of the drug.. In the future, in addition to sildenafil, the new phosphodiesterase 5 inhibitors vardenafil and tadalafil will play an important role in the management of erectile dysfunction, depending on the patient's health profile.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Since the early 1980s, research on the mechanisms of penile erection has done much to clarify erectile physiology and pathophysiology. More recent studies have identified the importance of neurochemical mediators in erection. These include the nitric oxide-cyclic guanosine monophosphate (cGMP) cell-signaling system-a complex molecular pathway that mediates smooth muscle relaxation in the corpus cavernosum. Phosphodiesterase 5 (PDE5) inactivates cGMP, which terminates nitric oxide-cGMP-mediated smooth muscle relaxation. Inhibition of PDE5 is expected to enhance penile erection by preventing cGMP degradation. Development of pharmacologic agents with this effect has closely paralleled the emerging science. The prototype of this new therapeutic class of PDE5 inhibitors is sildenafil, which was approved for treatment of erectile dysfunction in 1998. Tadalafil and vardenafil are new agents in this class. These agents have demonstrated improvement in erectile function and have been shown to be well tolerated in diverse populations comprising thousands of men worldwide. Profiles of these 3 PDE5 inhibitors are reviewed herein.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Vardenafil is a phosphodiesterase type-5 (PDE-5) inhibitor developed as an oral therapy for erectile dysfunction (ED). Multiple phase 3 clinical trials have been completed and vardenafil is expected to launch worldwide in 2003. Two pivotal, randomized, double-blind, multicenter studies have evaluated the use of vardenafil in men with ED. Vardenafil improved the rate of achieving and maintaining an erection during sexual intercourse. Improvement also was noted in other aspects of sexual function, including confidence, orgasmic function, and overall satisfaction. Vardenafil produces clinically and statistically significant improvements in erectile function regardless of age, baseline severity, and etiology and is efficacious for the treatment of ED in diabetic and postprostatectomy patients. Vardenafil has a rapid onset of action and completion of successful sexual intercourse is possible for some patients 16 minutes after its administration. Twenty milligrams of vardenafil has sustained long-term efficacy by providing up to 92% of patients with improved erections during more than 2 years of treatment. Vardenafil is well tolerated, with an adverse event profile typical of the class of PDE-5 inhibitors. The most common adverse events were headache, flushing, rhinitis, and dyspepsia, which were mild or moderate and generally decreased with continued treatment. Vardenafil may be associated with transient reductions in blood pressure and commensurate increases in heart rate, with the overall incidence of cardiovascular-related adverse events similar to that of placebo.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Administration Schedule; Drug Evaluation; Drug Tolerance; Erectile Dysfunction; Humans; Imidazoles; Male; Patient Satisfaction; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Vardenafil (Levitra), recently launched in Belgium by Bayer and Glaxo-SmithKline, is a new drug that potently and selectively inhibits phosphodiesterase type 5 (PDE5) in the cavernosum tissue of the penis. Inhibition of PDE5 blocks the hydrolysis of cyclic guanosine monophosphate (GMPc) and results in increased arterial blood flow leading to enlargement of the corpus cavernosum and resulting in erection. In controlled clinical trials, vardenafil at least doubled the rate of successful erections as compared to placebo, whatever the evaluation parameter considered and the subgroup of patients studied. Vardenafil is thus indicated in the treatment of patients with erectile dysfunction. It is presented as 5, 10 and 20 mg tablets and the usual dose is 10 mg to be ingested 25 to 60 minutes before sexual activity. Vardenafil has a more potent inhibitory activity of PDE5 in vitro than sildenafil or tadalafil while its pharmacokinetics in vivo is somewhat more rapid than that of the two other compounds. The dosage of vardenafil may be reduced to 5 mg (especially in older individuals) to improve tolerance or be increased up to 20 mg (especially in the presence of organic diseases aggravating erectile dysfunction) to improve efficacy. Contra-indications (co-administration with drugs increasing nitric oxide) and side-effects (headache and flushing due to vasodilatation) of vardenafil are similar to those of other PDE5 inhibitors.

Topics: Erectile Dysfunction; Humans; Imidazoles; Male; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Vardenafil (Levitra) is a potent and highly selective oral phosphodiesterase type 5 (PDE5) inhibitor. Vardenafil improved erectile function in men with mild to severe erectile dysfunction (ED) of varying aetiology in two randomised, double-blind, multicentre, fixed-dose studies of 12 or 26 weeks' duration. Men receiving vardenafil 10 or 20 mg had significantly greater improvements in International Index of Erectile Function (IIEF) questionnaire erectile function domain scores than placebo recipients. Moreover, improvements in penetration and maintenance of erection (assessed using IIEF or Sexual Encounter Profile [SEP] questions) were significantly greater with vardenafil 5-20 mg than with placebo. Improvements in IIEF intercourse satisfaction and orgasmic function domain scores were significantly greater with vardenafil 10 or 20 mg than with placebo and the proportion of patients with a positive response to a Global Assessment Question (GAQ) concerning improvement in erections after 12 or 26 weeks' therapy was significantly higher with vardenafil 5-20 mg than with placebo. Vardenafil improved erectile function in men with ED associated with diabetes mellitus or ED following unilateral or bilateral nerve-sparing radical retropubic prostatectomy in two randomised, double-blind, multicentre, fixed-dose, 3-month studies. In both studies, improvements from baseline in the erectile function domain score of the IIEF and in positive responses to SEP questions were significantly greater with vardenafil 10 or 20 mg than with placebo. In addition, a significantly higher proportion of vardenafil 10 or 20 mg recipients than placebo recipients had positive GAQ responses. Vardenafil was generally well tolerated in men with ED; treatment-emergent adverse events were of mild to moderate intensity and transient in nature. The most commonly reported adverse events (typical of those seen with PDE5 inhibitors) in vardenafil 5-20 mg recipients included headache, flushing, rhinitis, dyspepsia and sinusitis. There were no reports of abnormal colour vision in men with ED taking vardenafil at clinically recommended doses (5-20 mg).. Vardenafil is a potent and highly selective oral PDE5 inhibitor. It is effective and generally well tolerated in men with mild to severe ED of varying aetiology, as well as in men with ED associated with diabetes mellitus or ED after radical prostatectomy. Vardenafil should be considered a first-line treatment option in men with ED who are suitable candidates for oral PDE5 inhibitor therapy.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Randomized Controlled Trials as Topic; Sulfones; Triazines; Vardenafil Dihydrochloride

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Apomorphine; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Topics: alpha-MSH; Arginine; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Penile Erection; Peptides, Cyclic; Phosphodiesterase Inhibitors; Pinacidil; Piperazines; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Phosphodiesterase enzymes convert cyclic GMP and cyclic AMP to the corresponding nucleotide monophosphates. Phosphodiesterase 5 (PDE5) inhibition is now a widely accepted and efficacious therapeutic option for the treatment of erectile dysfunction in men, as a result of extensive clinical experience with sildenafil and other new PDE5 inhibitors. Research in the field continues at a substantial level to identify new, selective PDE5 inhibitors and to investigate their usefulness and activity in other areas. This review summarizes recent clinical trials with PDE5 inhibitors, advances in medicinal chemistry, and other activities and potential applications of this class of compounds.

Topics: Carbolines; Chemistry, Pharmaceutical; Clinical Trials as Topic; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Sildenafil Citrate; Structure-Activity Relationship; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) (impotence) is a widespread, age-related problem, which affects 52% of men between 40 and 70 years of age. It is classified as psychogenic, organic, or mixed psychogenic and organic. ED is not a problem only of men, because the relationship between partners can also be disturbed. Therefore, adequate treatment of ED is needed and the most convenient and simplest way is oral drug therapy. Sildenafil, phosphodiesterase-(PDE)-5-selective inhibitor has been the drug of choice for patients with ED since it has been launched in March 1998. The results of various studies have confirmed the efficacy of the drug in men with ED of various etiologies, as well as the positive effect of sildenafil on the quality of a partnership. The most frequent adverse effects documented with sildenafil usage are headache, flushes, dyspepsia, visual disturbances and nasal congestion/rhinitis. These adverse effects are dose-related, usually transient and mild, with low withdrawal rate. Several studies performed recently have shown that sildenafil is a safe and effective treatment of ED in patients with cardiovascular disease, who do not take nitrates or nitrate donors concomitantly. Other oral medications for ED include apomorphine, phentolamine, yohimbine, trazodone, testosterone and new PDE-5 inhibitors in Phase III clinical trials, such as vardenafil and tadalafil. It is obvious, according to recent data, that the concept of PDE-5 inhibition has a central position in oral pharmacotherapy of ED. However, larger clinical studies of efficacy and safety should be carried out using most of the other above-mentioned oral agents and these may also gain a place in the therapy of ED. There are no studies directly comparing sildenafil and other treatments of ED or assessing its role in combination with other therapies. According to the present knowledge, the quality of life, not only of patients but also of their sexual partners, will be improved significantly with sildenafil usage and this is an important precondition for overall health ofboth. Sildenafil is thus a highly effective peroral treatment for ED in patients without contraindications for its use, which can be considered as the firstline therapy with an acceptable risk-benefit ratio.

Topics: Administration, Oral; Adult; Erectile Dysfunction; Humans; Imidazoles; Intestinal Absorption; Male; Metabolic Clearance Rate; Middle Aged; Phentolamine; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tissue Distribution; Triazines; Vardenafil Dihydrochloride; Yohimbine

Vardenafil hydrochloride is a potent and highly selective inhibitor of phosphodiesterase Type 5 that increases blood flow to the penis during sexual stimulation and helps restore the ability to achieve and sustain an erection in men with erectile dysfunction. Vardenafil was developed specifically to be an effective and safe oral medication for the treatment of erectile dysfunction, with potential advances over existing therapies. This review summarises key findings during the rapid and aggressive development of this compound, from in vitro assays to Phase III trials with both broad and special populations. Emphasis is placed on the presentation of data that demonstrates the clinical effectiveness and safety of this agent which is anticipated to be available in 2003.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Clinical Trials as Topic; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

Since introduction of the PDE-5 inhibitor sildenafil 4 years ago, there has been a fundamental change in the treatment of erectile dysfunction (ED). Intracavernosal or intraurethral injections of vasoactive substances or penile implants as mechanical aids now play hardly any part in it. - The development of the PDE-5 inhibitors vardenafil and tadalafil prompts the question of whether and how these three substances differ in terms of their efficacy and adverse effects. - Sildenafil has proven to be a very effective medicinal product. Studies with a follow-up period of up to 6 years have been conducted. The success rate of sildenafil varies in the group of ED patients with an organic underlying disease from 43% in patients who have undergone radical prostatectomy to 85% in patients with a neurological underlying disease, and amounts to an average 82% (range 43-85%, 100mg). - In an evaluation of spontaneous reports of deaths associated with sildenafil, the FDA concluded that there was no deducible evidence of an increase in the mortality rate among sildenafil users compared to the general population. In fact, fewer deaths associated in time with the ingestion of sildenafil were reported than might have been expected purely statistically on the basis of the normal mortality rate for men in this age group. - According to the initial studies conducted, vardenafil and tadalafil demonstrate efficacy data approximately comparable to those of sildenafil. As yet, insufficient data are available to evaluate the adverse effects of vardenafil and tadalafil, particularly their long-term use and use in high-risk groups. - Sildenafil has already been used by over 20 million men in over 110 countries and is one of the best-studied pharmacological substances available. This adventage in terms of knowledge and safety data makes sildenafil a safe and reliable treatment for patients with erectile dysfunction.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Contraindications; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Prevalence; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Phosphodiesterase type-5 (PDE-5) inhibitors are a new class of vasoactive drugs that have been developed for treatment of erectile dysfunction (ED). The mechanism of action involves active inhibition of the PDE-5 enzyme and resulting increase in cyclic guanosine monophosphate (cGMP) and smooth muscle relaxation in the penis. Sildenafil citrate (Viagra) is a potent and selective PDE-5 inhibitor, which is the first drug in this class to be approved for treatment of ED. More than 10 million men worldwide have been treated with this drug. Sildenafil has been shown to be generally effective in the treatment of ED, although the degree of efficacy varies according to the etiology and severity of the disorder. The drug is well tolerated, with relatively few contraindications (e.g., nitrates) and safety risks. The cardiovascular effects of sildenafil, in particular, have been extensively investigated. The results of recent studies suggest that sildenafil may have an additional role in the treatment of other male and female sexual disorders, such as premature ejaculation and female sexual arousal disorder, although results to date are inconclusive. Two additional agents in this class (tadalafil [Cialis], vardenafil [Levitra]) have been developed recently and are under regulatory review. Tadalafil is a long-acting PDE-5 inhibitor, which is effective for up to 36 hr in the majority of men. Vardenafil has a similar duration of action to sildenafil, but is more potent and selective biochemically. Both drugs appear to be generally safe and well tolerated, with a similar side-effect profile to sildenafil. There are no controlled comparison studies to date. Despite the overall effectiveness of PDE-5 inhibitors in the treatment of ED, significant psychological and interpersonal issues need to be addressed in their clinical use. The potential impact on societal attitudes toward sexuality and sexual dysfunction also warrants consideration.

Topics: Carbolines; Clinical Trials as Topic; Cyclic GMP; Erectile Dysfunction; Female; Humans; Imidazoles; Male; Muscle, Smooth; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Vardenafil, a potent and selective phosphodiesterase 5 inhibitor, has entered phase 3 clinical trials. Pharmacodynamic studies showed that the maximum plasma concentration after oral administration of 20-40 mg of vardenafil occurred in 0.7-0.9 h, the half-life was 4-5 h, and negligible amounts remained in the circulation after 24 h. The efficacy of vardenafil compared with placebo was shown in RigiScan studies, a phase 2 study involving 601 men with mild-to-severe erectile dysfunction for at least 6 months, and a phase 3 study involving 452 diabetic men. Adverse effects were not severe and tended to decrease with time.

Topics: Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

Vardenafil selectively inhibits phosphodiesterase type 5 (PDE5), an enzyme which hydrolyses cyclic guanosine monophosphate in the cavernosum tissue of the penis. Inhibition of PDE5 results in increased arterial blood flow leading to enlargement of the corpus cavernosum. Because of the increased tumescence, veins are compressed between the corpus cavernosum and the tunica albuginea, resulting in an erection. Vardenafil has a high bioavailabilty and is rapidly absorbed. An erection of >60% rigidity was maintained for approximately twice as long following visual stimulation in patients treated with vardenafil 10 or 20mg than in recipients of placebo. In a large, placebo-controlled trial in patients with mild to severe erectile dysfunction (ED), vardenafil 5, 10 or 20mg taken as needed over a 12-week period significantly improved the scores in questions 3 and 4 of the International Index of Erectile Function (IIEF). The rate of successful attempts at intercourse with ejaculation was also significantly higher with vardenafil (71 to 75%) than in the placebo group (39.5%), and significantly more patients treated with vardenafil than placebo responded 'yes' to a Global Assessment Question (GAQ) asking if treatment had improved erections. In a 26-week trial in 736 men with ED of varied aetiologies and severity patients receiving vardenafil 5, 10 or 20mg experienced significantly improved erections with 85% of vardenafil 20mg recipients reporting improved erectile function (assessed using the GAQ) compared with 28% of placebo recipients. Treatment with vardenafil also significantly improved scores in response to questions 3 and 4 of the IIEF compared with placebo. A 12-week trial in 452 men with ED associated with diabetes mellitus demonstrated that treatment with vardenafil 20mg compared with placebo significantly improved IIEF erectile function domain scores and the rate of positive responders to the erectile improvement GAQ. Similar results were reported in a placebo-controlled trial of vardenafil 10 to 20mg involving 440 patients with ED after radical prostatectomy. Adverse events associated with vardenafil were those commonly associated with PDE5 inhibitors: headache, flushing, dyspepsia and rhinitis. These were mostly dose-dependent and mild to moderate in intensity.

Topics: Clinical Trials as Topic; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

Bayer is developing vardenafil, an orally active phosphodiesterase (PDE) 5 inhibitor for the potential treatment of erectile dysfunction (ED) [314382]. NDAs were filed in September 2001 in the US and Mexico [423096], and vardenafil was submitted for Canadian approval in October 2001. As of November 2001, Bayer was expecting a response from the FDA in the second half of 2002 [429499]; the EMEA accepted a filing in January 2002, following a December 2001 submission [438163]. By October 2000, phase III trials were underway in Japan [384751] and by December 2001, a Japanese NDA had been filed; at the same time an application was filed in South Africa [426526], [433060]. At this time Japanese launch was expected in 2003 [434758]. By February 2001, Bayer was also investigating a nasal formulation of vardenafil for the potential treatment of erectile dysfunction [397608]. In November 2001, Bayer and GlaxoSmithKline signed a worldwide copromotion agreement for vardenafil, under which Bayer was to be responsible for all regulatory work required to obtain approval [429499]. In February 1999, Lehman Brothers predicted a 10% probability that vardenafil would reach the market, with launch in 2002. Peak Japanese sales of US$600 million were predicted for 2014 [319225]. In May 2000, Bayer predicted peak sales of Euro900 million [397137]. In July 2001, Lehman Brothers predicted a 75% chance that vardenafil would reach the market, and forecast peak sales of US $0.85 billion worldwide; the analyst also speculated that Bayer would seek a comarketing partner [414766].

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Administration, Oral; Animals; Clinical Trials as Topic; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Structure-Activity Relationship; Sulfones; Triazines; Vardenafil Dihydrochloride

The anesthetized rabbit model is useful and has many advantages: ability to perform neurophysiological studies; more administration routes, including intracavernous injection; haemodynamic measurements in parallel to measurements of intracavernous pressure or penile volume; and direct measurement of intracavernosal pressure and blood flow. This model has been evaluated with many different types of drugs. The conscious rabbit model is a simple and valid model for the assessment of compounds with potential for treatment of ED. It offers several methodological advantages as a screening model for compounds with erection stimulating properties. It was clearly successful in demonstrating the efficacy and the mechanism of the new potent and selective PDE5 inhibitor vardenafil. The model was also effective in demonstrating erection-generating properties through other mechanisms, eg PDE3 inhibitors and alpha-receptor blockers. In conclusion, both anaesthetized rabbit model and the newly developed conscious-rabbit models are well-suited for studies in impotence research.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Cyclic Nucleotide Phosphodiesterases, Type 5; Diabetes Mellitus, Experimental; Disease Models, Animal; Erectile Dysfunction; Imidazoles; Male; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Rabbits; Research; Sulfones; Triazines; Vardenafil Dihydrochloride

Topics: Adrenergic alpha-Antagonists; Alprostadil; Apomorphine; Erectile Dysfunction; Humans; Hypogonadism; Imidazoles; Male; Penile Implantation; Physical Therapy Modalities; Piperazines; Psychotherapy; Purines; Sildenafil Citrate; Sulfones; Testosterone; Triazines; Vacuum; Vardenafil Dihydrochloride; Vascular Surgical Procedures; Vasodilator Agents; Yohimbine

Oral vardenafil (VDF) tablet is an effective treatment for erectile dysfunction (ED), but intranasal administration with a suitable formulation can lead to a faster onset of action and offer more convenient planning for ED treatment.. The primary purpose of the present pilot clinical study was to determine whether intranasal VDF with an alcohol-based formulation can result in more "user-friendly pharmacokinetics" as compared with oral tablet administration.. This single-dose randomized crossover study was conducted in 12 healthy young volunteers receiving VDF as a 10-mg oral tablet or 3.38-mg intranasal spray. Multiple blood concentrations were obtained, and VDF concentrations were determined with a liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters following each treatment were compared and adverse events assessed.. Pharmacokinetic parameters were obtained: apparent elimination rate constant, elimination half-life, peak concentration, peak time, total area under the curve, and relative bioavailability.. Although mean apparent elimination rate constant, elimination half-life, peak concentration, and total area under the curve were similar between intranasal and oral administration, the median peak time from intranasal was much shorter (10 vs 58 minutes, P < .001, Mann-Whitney U test). The variability of the pharmacokinetic parameters was also less with intranasal than oral administration. The relative bioavailability of intranasal to oral was 1.67. Intranasal VDF caused transient but tolerable local nasal reactions in 50% of subjects. Other adverse events (eg, headache) were similar between the treatments. The incidence of adverse events was, however, significantly less in the second treatment after initial exposure to VDF. No serious adverse events were noted.. Intranasal VDF potentially offers a more timely and lower dose for the treatment of ED in patients who can tolerate the transient local adverse reactions.. The strength of this study is its randomized crossover design. Because the study was conducted in 12 healthy young subjects, the results may not reflect those observed in elderly patients who may be likely taking VDF for ED. Nevertheless, the changes of pharmacokinetic parameters in the present study are likely a reflection of the differences between intranasal and oral administration of the formulations.. Our study indicated that the present VDF formulation, when administered intranasally, can achieve a more rapid but similar plasma concentration with only about one-third dose when compared with the oral administration.

Topics: Administration, Intranasal; Administration, Oral; Aged; Area Under Curve; Biological Availability; Cross-Over Studies; Erectile Dysfunction; Humans; Male; Tablets; Vardenafil Dihydrochloride

Erectile function is important for life satisfaction and often impaired in men with obstructive sleep apnea (OSA). Uncontrolled studies show that treating OSA with continuous positive airway pressure (CPAP) improves erectile function. Phosphodiesterase type 5 inhibitors (e.g., vardenafil) are the first-line therapy for erectile dysfunction (ED), but may worsen OSA.. To assess the effects of CPAP and vardenafil on ED.. Sixty-one men with moderate-to-severe OSA and ED were randomized to 12 weeks of CPAP or sham CPAP, and 10 mg daily vardenafil or placebo in a two-by-two factorial design.. International Index of Erectile Function (primary end point), treatment and relationship satisfaction, sleep-related erections, sexual function, endothelial function, arterial stiffness, quality of life, and sleep-disordered breathing.. CPAP increased the frequency of sleep-related erections, overall sexual satisfaction, and arterial stiffness but did not change erectile function or treatment or relationship satisfaction. Vardenafil did not alter erectile function, endothelial function, arterial stiffness, or sleep-disordered breathing, but did improve overall self-esteem and relationship satisfaction, other aspects of sexual function, and treatment satisfaction. Adherent CPAP improved erectile function, sexual desire, overall sexual, self-esteem, relationship, and treatment satisfaction, as well as sleepiness, and quality of life. Adherent vardenafil use did not consistently change nocturnal erection quality.. CPAP improves overall sexual satisfaction, sleep-related erections, and arterial stiffness. Low-dose daily vardenafil improves certain aspects of sexual function and did not worsen OSA. Adherent CPAP or vardenafil use further improves ED and quality of life.

Topics: Adult; Aged; Combined Modality Therapy; Continuous Positive Airway Pressure; Erectile Dysfunction; Humans; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase 5 Inhibitors; Quality of Life; Sexual Behavior; Sleep Apnea, Obstructive; Treatment Outcome; Vardenafil Dihydrochloride

We conducted a prospective study of transient evoked otoacoustic emissions (TEOAEs) and distortion-product otoacoustic emissions (DPOAEs) in men who were taking an oral phosphodiesterase type 5 (PDE5) inhibitor for erectile dysfunction. Our study group was made up of 30 men (60 ears), aged 34 to 60 years (mean: 50.9). They were randomly divided into three groups; 10 men were given sildenafil (Viagra) at 50 mg twice a week, 10 were given tadalafil (Cialis) at 20 mg twice a week, and 10 were given vardenafil (Levitra) at 20 mg twice a week. All patients took their drug for 3 weeks, for a total of 6 tablets for each patient. Audiometric tests and TEOAE and DPOAE measurements were performed before and after treatment. Post-treatment audiometry demonstrated improvement in hearing in all three groups. However, post-treatment TEOAE amplitudes and DPOAE amplitudes differed among the three groups; they were significantly higher in the sildenafil group at 1.0 kHz and the same in the tadalafil group; in the vardenafil group, the DPOAE amplitude was significantly lower at 3.0 kHz while there was no change in the TEOAE amplitude. We speculate that the possible mechanism for these findings is that PDE5 inhibitors block degradation of cyclic guanosine monophosphate (cGMP) and induce dilation of the cochlear microcirculation, resulting in an increase in cochlear blood flow. We also believe that the decrease in DPOAE amplitudes at 3.0 kHz seen in the vardenafil group may be related to an accumulation of nitric oxide/cGMP complex, which is toxic to the cochlea; however, since there was no change in TEOAE amplitude in the vardenafil group, this influence may be minimal. Further studies are needed to obtain a more comprehensive assessment of the effects of PDE5 inhibitors on hearing with the use of higher doses and longer durations of therapy.

Topics: Adult; Audiometry; Cochlea; Erectile Dysfunction; Hearing; Humans; Male; Middle Aged; Otoacoustic Emissions, Spontaneous; Phosphodiesterase 5 Inhibitors; Prospective Studies; Sildenafil Citrate; Vardenafil Dihydrochloride

Type 2 diabetes mellitus (T2DM) is associated with endothelial dysfunction, characterized by a reduction of nitric oxide (NO)-mediated relaxation. Phosphodiesterase type 5 inhibitors (PDE5i) improve NO levels. The aim of the study was to investigate whether long-term, chronic treatment with the PDE5i vardenafil improves systemic endothelial function in diabetic men.. A prospective, investigator-initiated, randomized, placebo-controlled, double-blind, clinical trial was conducted.. In total, 54 male patients affected by T2DM, diagnosed within the last 5 years, and erectile dysfunction were enrolled, regardless of testosterone levels. In all, 26 and 28 patients were assigned to verum and placebo groups respectively. The study consisted of an enrollment phase, a treatment phase (24 weeks) (vardenafil/placebo 10  mg twice in a day) and a follow-up phase (24 weeks). Parameters evaluated were as follows: International Index of Erectile Function 15 (IIEF-15), flow-mediated dilation (FMD), serum interleukin 6 (IL6), endothelin 1 (ET-1), gonadotropins and testosterone (measured by liquid chromatography/tandem mass spectrometry).. IIEF-15 erectile function improved during the treatment (P<0.001). At the end of the treatment both FMD (P=0.040) and IL6 (P=0.019) significantly improved. FMD correlated with serum testosterone levels (R(2)=0.299; P<0.001). Testosterone increased significantly under vardenafil treatment and returned in the eugonadal range only in hypogonadal men (n=13), without changes in gonadotropins. Chronic vardenafil treatment did not result in relevant side effects.. This is the first double-blind, placebo-controlled clinical trial designed to evaluate the effects of chronic treatment of vardenafil on endothelial health-related parameters and sexual hormones in patients affected by a chronic disease. Chronically administered vardenafil is effective and improves endothelial parameters in T2DM patient. Moreover, chronic vardenafil therapy improves hypogonadism in diabetic, hypogonadal men.

Topics: Aged; Biomarkers; C-Reactive Protein; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Schedule; Endothelium, Vascular; Erectile Dysfunction; Humans; Hypogonadism; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Longitudinal Studies; Male; Middle Aged; Time Factors; Vardenafil Dihydrochloride; Vascular Cell Adhesion Molecule-1

Delivery of vardenafil (for improvement of erectile function) via the inhaled route of administration may be advantageous in that this avoids extensive first pass metabolism and may therefore increase the bioavailability (hence the reliability of absorption) and shorten the time of pharmacological onset of activity. A unique nebulizer design has been developed by the sponsor (Advanced Medical Institute Pty Ltd) that is capable of delivering relatively large volumes of drug.. The primary objective of the Phase 1 study was to assess and compare the pharmacokinetics of a single dose of vardenafil 10-mg tablet and a single dose of vardenafil solution administered via inhalation using an ultrasonic nebulizer device. Secondary objective was to assess the safety of vardenafil administered via inhalation using an ultrasonic nebuliser device.. Two-part study in healthy volunteers. Dose-ranging study was performed in two subjects to determine the appropriate inhalational dose, followed by an open, randomized, crossover, single dose pharmacokinetic study in 12 subjects, which compared a single 10-mg oral dose to the inhalation dose.. Cmax, Cmax/Dose, Tmax, ke, t1/2, AUC0-t, AUCt-∞, AUC0-∞, AUC0-∞, AUC0-∞/Dose, and % area extrapolated.. The two treatments are not bioequivalent, with vardenafil absorbed and eliminated faster and with less variability using the nebulizer for drug delivery. Administration via the inhalational route was not associated with any clinically significant changes in blood pressure or heart rate, and no serious adverse events were recorded, demonstrating an acceptable safety profile.. To our knowledge, this is the first report of the administration of vardenafil HCl via the pulmonary route of administration. This trial demonstrates that vardenafil HCl may be administered using the ultrasonic nebulizer to reach blood levels comparable with those produced by a vardenafil 10-mg oral tablet, faster and using less drug. This new route of administration may potentially improve the onset of action, reliability, and safety for this class of drug.

Topics: Administration, Oral; Adult; Area Under Curve; Cross-Over Studies; Erectile Dysfunction; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Reproducibility of Results; Tablets; Ultrasonics; Vardenafil Dihydrochloride; Vasodilator Agents; Young Adult

Phosphodiesterase type-5 inhibitors (PDE5Is) are first-line therapies for erectile dysfunction (ED). Sildenafil (SIL) and vardenafil (VAR) are approved for as-needed (PRN) dosing; tadalafil (TAD) is approved for both PRN and once-a-day (OaD) dosing for ED. Recent evidence suggests that TAD-OaD may be effective as therapy in men with an incomplete response to PRN-PDE5I therapy. This study evaluated whether TAD-OaD provides similar efficacy in men with ED who had previously demonstrated a partial response to PRN-PDE5I therapy.. In this randomized, double-blind, placebo-controlled trial, men with a ≥3 month ED history received SIL 100 mg, TAD 20 mg, or VAR 20 mg during a 4 week open-label lead-in period. Those with International Index of Erectile Function - Erectile Function (IIEF-EF) domain scores <26 following lead-in treatment completed a 4 week washout period, then randomized to TAD 2.5 mg up-titrated to 5 mg, TAD 5 mg, or placebo (PBO) OaD for 12 weeks. MAIN OUTCOME MEASURES obtained from patients treated with TAD-OaD were compared to PBO-treated patients. Additionally, results of treatment with TAD-OaD were compared to results obtained from 4 week PRN-PDE5I therapy to determine whether OaD and PRN regimens provided comparable efficacy.. NCT01130532.. International Index of Erectile Function (IIEF) domain scores; Sexual Encounter Profile (SEP) questions 2-5.. Endpoint data was obtained from 590 men (391 TAD; 199 PBO). RESULTS for all IIEF and SEP measures were significantly better for TAD-OaD (p < 0.001 for all) compared to PBO and were comparable to those observed during PRN-PDE5I treatment. TAD 2.5 mg and TAD 5 mg OaD therapy were safe and generally well tolerated.. Tadalafil once daily is a viable alternative to as-needed PDE5I therapy in men with ED. Key limitations include the lack of a PRN PDE5I study group during the double-blind period, and that many more patients took tadalafil than sildenafil or vardenafil during the PRN period.

Topics: Adult; Carbolines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Monitoring; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Preference; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Erectile Dysfunction is considered a multifactorial disease, where organic and psychological aspects are often interconnected. In a randomized controlled pilot study, we compared the efficacy of combined vardenafil orodispersible tablet (VARD) and cognitive-behavioral sex therapy (CBST) vs. VARD alone in improving sexual symptoms in both male and female partners. Thirty male patients with erectile dysfunction, and their partners were randomly assigned with a 2 : 1 ratio, to two different arms and treated for 10 weeks with VARD (Group A; n = 19) or VARD+CBST (Group B; n = 11). International Index of Erectile Dysfunction (IIEF-15), Female Sexual Function Index (FSFI) and Index of Sexual Satisfaction (ISS) were, respectively, administered to male, female, and both partners at times (T) 0, 1 (+5 weeks of therapy) and 2 (+10 weeks of therapy). Groups A and B were similar in their sociodemographic and clinical characteristics. Pre-treatment (T0) test scores did not significantly differ among the groups. In both group A and B, the IIEF-Erectile Function domain showed a significant improvement from T0 to T1 (p = 0.005 and p < 0.0001 vs. T0, respectively) and from T0 to T2 only in group B (p = 0.013). In group A, FSFI and both male and female ISS did not show any significant change at T1 and T2 vs. T0. In group B, a significant improvement at final time-point in FSFI and male and female ISS scores was reported (p < 0.05, T2 vs. T0 in all scores). The results of our study suggest that both VARD alone and VARD+CBST improved erectile function, however, only VARD+CBST improved couple sexual satisfaction and female sexual function.

Topics: Adult; Cognitive Behavioral Therapy; Coitus; Erectile Dysfunction; Female; Humans; Male; Middle Aged; Patient Satisfaction; Penile Erection; Pilot Projects; Self Report; Sexual Behavior; Surveys and Questionnaires; Treatment Outcome; Vardenafil Dihydrochloride

An optimal outcome of an erectile dysfunction (ED) treatment is to enable a return to normal erectile function (as defined by an International Index of Erectile Function-Erectile Function [IIEF-EF] domain score ≥ 26). As-needed (PRN) phosphodiesterase type 5 (PDE5) inhibitor treatment does not always result in a return-to-normal erectile function.. The combined studies evaluated whether treatment with tadalafil once daily would allow men to return to normal erectile function who had less than normal IIEF-EF domain scores while using a maximum dose of a PRN PDE5 inhibitor treatment.. Men were ≥ 18 years of age, sexually active, reported a ≥ 3-month history of ED, and had been taking the maximum dose of sildenafil citrate, vardenafil, or tadalafil PRN. Randomization to once-daily therapy with tadalafil 2.5 mg to 5 mg (N = 207), tadalafil 5 mg (N = 207), or placebo (N = 209) for 12 weeks followed a 4-week maximum dose PRN PDE5 treatment and 4-week nondrug lead periods. Two identical double-blind, randomized, placebo-controlled studies were conducted; combined results are reported.. The main outcome measure was the percentage of subjects with a return-to-normal erectile function (IIEF-EF domain score ≥ 26) when treated with tadalafil once daily compared with placebo.. In subjects not achieving normal erectile function with the maximum dose of a PRN PDE5 inhibitor, a higher percentage of subjects treated with tadalafil had an IIEF-EF domain score ≥ 26 at end point (tadalafil 2.5- to 5-mg group [39%]; tadalafil 5-mg group [40%]) compared with the placebo group (12.1%; P < 0.001). Tadalafil was generally well tolerated and adverse events observed were consistent with previous reports of tadalafil once daily.. Treatment with tadalafil once daily significantly improved erectile function in men with mild to mild-moderate impairments in erectile function following PRN PDE5 inhibitor treatment.

Topics: Carbolines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Penile Erection; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Stopwatch-assessed duration of erection has been proposed as an objective and reliable efficacy end point for erectile dysfunction (ED) treatments.. The aim of this study is to assess vardenafil orodispersible tablets' (ODTs) efficacy in terms of duration of erection and (i) its correlation with other efficacy end points and male and female sexual quality of life (QoL) and (ii) its impact on intercourse duration.. Randomized, double-blind, placebo-controlled, multicenter study comparing the efficacy and safety of vardenafil ODT 10 mg on-demand over 12 weeks in 127 patients with ED was carried out.. Primary efficacy end points were stopwatch-assessed duration of erection (min) at any attempt and when leading to successful intercourse, and the erectile function domain of the International Index of Erectile Function (EF-IIEF) score. Secondary end points were sexual encounter profile (SEP) 3 response rate and male sexual QoL. End points in participating women (N = 46) were stopwatch-assessed duration of intercourse and sexual QoL.. At week 12/last observation carried forward, patients taking vardenafil ODT had longer duration of erections (at any attempt or leading to successful intercourse) vs. placebo (least square mean ± standard error 10.2 ± 0.9 minutes vs. 7.9 ± 1.0 minutes, and 10.4 ± 0.8 vs. 8.3 ± 1.0 minutes, respectively), and significant increases in EF-IIEF scores, the SEP-3 response, and all sexual QoL items. An increased duration of intercourse was also observed. Female sexual QoL improved significantly. Both duration end points strongly correlated with EF-IIEF scores, and the three end points correlated well with SEP-3 response. Correlation was good with sexual QoL scores in men and women and with duration of intercourse, with differences between treatment groups only for duration end points. Safety was similar in both groups.. This study provides further evidence for the consistency and reliability of the stopwatch-assessed duration of erection as an efficacy end point for ED treatments, with "duration of erection leading to successful intercourse" showing better properties than duration at any attempt.

Topics: Adult; Coitus; Double-Blind Method; Erectile Dysfunction; Female; Humans; Imidazoles; Male; Middle Aged; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Quality of Life; Reproducibility of Results; Sexual Behavior; Sexual Partners; Sulfones; Tablets; Time Factors; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Evidences have been suggested that phosphodiesterase type 5 (PDE5) inhibition promotes vasculoprotective benefits in patients with cardiovascular diseases.. The aim of this study is to analyze the systemic effect of PDE5 inhibition in type 2 diabetes mellitus patients with erectile dysfunction (ED) determining changes in the expression levels of plasma proteins.. Seventeen patients with controlled type 2 diabetes mellitus and ED were included in the study. Patients received vardenafil hydrochloride 20 mg on demand during 12 weeks. At the beginning and 12 weeks after vardenafil administration, plasma samples were collected and analyzed using proteomics.. International Index of Erectile Function-Erectile Function Domain (IIEF-EFD) and plasma protein expression before and after vardenafil administration. Nitrate/nitrite release, PDE5, and soluble guanylate cyclase (sGC) expression and cyclic guanosine monophosphate (cGMP) content in cultured bovine aortic endothelial cells (BAECs).. The IIEF-EFD score was markedly improved after 12 weeks of vardenafil administration. Plasma levels of alpha 1-antitrypsin isotypes 4 and 6 and β-tropomyosin were decreased, whereas apolipoprotein AI isoype 5 was increased 12 weeks after vardenafil administration. Only β-tropomyosin plasma levels were inversely correlated with IIEF-EFD score. Tropomyosin has been added to cultured BAECs and after 24 hours reduced the protein expression level of sGC-β1 subunit and decreased the cGMP content. Tropomyosin did not modify PDE5 expression and nitric oxide release in BAECs as compared with control BAECs. Vardenafil (10 μg/mL) did not modify sGC-β1 subunit expression in tropomyosin + vardenafil-incubated BAECs; however, vardenafil significantly reversed the reduction of cGMP content induced by tropomyosin.. Vardenafil administration improved erectile functionality in controlled type 2 diabetes mellitus patients with ED, which was associated with reduction of circulating plasma β-tropomyosin levels. Tropomyosin affected by itself the cGMP generating system suggesting a possible new mechanism involved in ED. Vardenafil reversed the reduction effect of cGMP content elicited by tropomyosin in BAECs.

Topics: Animals; Cattle; Cyclic GMP; Diabetes Mellitus, Type 2; Erectile Dysfunction; Guanylate Cyclase; Humans; Imidazoles; Male; Middle Aged; Nitric Oxide; Penile Erection; Phosphodiesterase 5 Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Receptors, Cytoplasmic and Nuclear; Soluble Guanylyl Cyclase; Sulfones; Triazines; Tropomyosin; Vardenafil Dihydrochloride

Although vardenafil is widely prescribed for erectile dysfunction (ED), its effect on arterial function is not defined. Aortic stiffness, aortic pressures, and wave reflections are predictors of cardiovascular risk. The investigators assessed the hypothesis that vardenafil acutely improves aortic stiffness, aortic pressures, and wave reflections in ED patients. Twelve ED patients (mean age 58 ± 9 years) received vardenafil 20 mg in a randomized, placebo-controlled, double-blind, 2-way crossover design. Aortic stiffness was evaluated with carotid-femoral pulse wave velocity (PWV); wave reflections and aortic pressures were evaluated with augmentation index (AIx) and systolic, diastolic, and pulse pressure of the aortic pressure waveform, respectively. PWV, aortic pressures, and AIx were measured at baseline and for 3 hours after vardenafil intake or placebo. PWV decreased significantly (by 0.7 m/s, P = .001), denoting a decrease in aortic stiffness. AIx decreased significantly (by 7%, P = .008), denoting a decreased effect of wave reflections from the periphery. Aortic pressures decreased significantly (all P < .05). Statin use at baseline significantly interacted with the effects of treatment on both PWV and AIx (P = .003 and P < .001, respectively). This study shows, for the first time, that vardenafil has a favorable acute effect on aortic stiffness and wave reflection in ED patients.

Topics: Aorta; Arterial Pressure; Blood Pressure; Cardiovascular Diseases; Cross-Over Studies; Double-Blind Method; Erectile Dysfunction; Heart Rate; Humans; Imidazoles; Male; Middle Aged; Piperazines; Pulse Wave Analysis; Sulfones; Triazines; Vardenafil Dihydrochloride; Vascular Stiffness

Several treatment regimens for rehabilitation of erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) are currently discussed. The optimal and most cost-effective therapy is still not found yet.. To evaluate the effect of vardenafil, a PDE5 inhibitor, dose escalation on recovery of EF after unilateral nsRP.. Thirty-six sexually active patients received a unilateral nsRP. All patients completed an International Index of Erectile Function-5 items (IIEF-5) questionnaire concerning EF preoperatively. Group 1 (N = 12 patients) received vardenafil 5 mg/day vs. group 2 (N = 12) who received vardenafil 10 mg/day at night beginning the day of catheter removal. A control of 12 patients underwent follow-up without PDE5 inhibitors.. The IIEF-5 was the primary end point. IIEF-5 questionnaires were completed at baseline, 3, 6, and 12 months after nsRP.. In group 1 (5 mg/day vardenafil) the IIEF-5 score decreased from a preoperative 22.4 mean score to 4.2 at 3 months, 8.9 at 6 months, and 13.4 mean score at 12 months after nsRP vs. preoperative 22.8, 4.1 at 3 months, 7.9 at 6 months, and 12.8 mean score at 12 months in group 2 (10 mg/day vardenafil). In the control group the preoperative IIEF-5 mean score of 21.9 decreased to 3.8 at 3 months, 6.1 at 6 months, and 8.9 at 12 months. Statistical evaluation showed significant difference in IIEF-5 score and time to recovery of EF between groups 1 and 3 and between groups 2 and 3 (P < 0.01). No statistical differences were found between groups 1 and 2.. Daily low-dose vardenafil lead to significant improvement of recovery of EF. In this study doubling the dosage did not improve the recovery of EF further.

Topics: Aged; Dose-Response Relationship, Drug; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Penile Erection; Phosphodiesterase 5 Inhibitors; Piperazines; Prostatectomy; Sulfones; Surveys and Questionnaires; Triazines; Vardenafil Dihydrochloride

Safety and efficacy of tamsulosin and vardenafil are well established: however, there is no report regarding combined therapy with these drugs for lower urinary tract symptoms (LUTSs) secondary to benign prostatic hyperplasia (BPH).. To compare the safety and efficacy of tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus vardenafil 10 mg/day in patients with LUTS/BPH in a randomized trial with 12-week follow-up.. We conducted a randomized, double-blind, placebo-controlled study on 60 men with persistent storage LUTS after 2-week run-in with tamsulosin.. International Prostate Symptom Score (IPSS), IPSS-bother, International Index of Erectile Function, Version 5 (IIEF-5) and Over Active Bladder questionnaire (OAB-q) scores, uroflowmetry data (Qmax, Qave), and postvoiding residual urine were recorded after run-in (baseline), and 2 and 12 weeks after treatment. Differences between vardenafil and placebo at different times were calculated with unpaired samples t-test. Between-group differences in change from baseline to 2 and 12 weeks were evaluated with analysis of variance.. We found a between-group significant difference from baseline to 12 weeks in the following: (i) Qmax (placebo: +0.07, vardenafil: +2.56, P = 0.034); (ii) Qave (placebo: -0.15, vardenafil: +1.02, P = 0.031); (iii) irritative-IPSS subscores (placebo: -1.67, vardenafil: -3.11, P = 0.039); and (iv) IIEF (placebo: +0.06, vardenafil: +2.61, P = 0.030). No patient reported any serious (grade ≥ 2) adverse event (AE). There were no differences in the incidence of common, treatment-related AEs between men undergoing combined therapy or tamsulosin alone.. The combination of tamsulosin and vardenafil for 12 weeks was well tolerated and more effective to improve both LUTS and erectile function, as compared with tamsulosin alone. Further studies are needed to assess the role of combined therapy of phosphodiesterase type 5 inhibitors and alpha blockers in treating LUTS/BPH.

Topics: Adrenergic alpha-1 Receptor Antagonists; Aged; Double-Blind Method; Drug Therapy, Combination; Erectile Dysfunction; Humans; Imidazoles; Lower Urinary Tract Symptoms; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Prostatic Hyperplasia; Sulfonamides; Sulfones; Tamsulosin; Triazines; Vardenafil Dihydrochloride

To evaluate whether the response to on-demand vardenafil could be improved by its daily usage in hypertensive men with erectile dysfunction (ED) who previously did not answer to on-demand regime.. Our main efficacy criterion was per patient percentage of positive answers on the Sexual Encounter Profile question 3 (SEP3). Carotid intima-media thickness (IMT), flow-mediated dilation (FMD), and nitrate-mediated dilation on brachial artery were considered as vascular parameters. A total of 74 hypertensive men with ED aged 50 to 70 years with no major cardiovascular disease were selected from 284 patients initially referred. After vardenafil on-demand usage during 4 weeks, patients with more than 50% of positive answers on the SEP3, or 50% and more than 6 points on the International Index of Erectile Function-Erection Function Domain (IIEF-EF) basal score or positive answer to global evaluation question were considered "responders." "Nonresponders" (n = 35) were randomized to daily vardenafil 10 mg or placebo during 5 weeks along with open 10 mg of vardenafil before intercourse.. In the active group, 38.8% of patients became responders to vardenafil (P < .05). Clinical response to continuous vardenafil correlated with sexual frequency (r = .68, P < .01), Framingham risk score (r = -.65, P < .01), carotid IMT (r = -.61, P = .01) and low-density lipoprotein (LDL)-cholesterol (r = -.64, P < .01).. Daily vardenafil during 5 weeks rescued response to on-demand regime among ED hypertensive men with no major cardiovascular disease. Further clinical trials and cost-effectiveness studies are necessary to confirm these findings.

Topics: Aged; Blood Glucose; Brachial Artery; Carotid Intima-Media Thickness; Cholesterol, LDL; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Logistic Models; Male; Middle Aged; Multivariate Analysis; Nitrates; Phosphodiesterase 5 Inhibitors; Piperazines; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To investigate the effects of phosphodiesterase type 5 (PDE5) inhibitors on erectile variables during a period with no sexual stimulation in a laboratory setting double-blind study.. In all, 80 men without erectile dysfunction (ED) but with lifelong premature ejaculation (PE) were included in the study. The men were divided equally in to four groups and received either placebo, vardenafil (10 mg), sildenafil (50 mg) or tadalafil (20 mg) in a double-blind study design. The men attended the laboratory following 3 days of sexual abstinence and placebo or one of the PDE5 inhibitors was ingested after ≥ 2 h of fasting and non-smoking. The men were then immediately placed in a silent room and real-time penile rigidity and tumescence monitoring with Rigiscan Plus (Rigiscan Plus® System, Osbon Medical Systems, Augusta, GA, USA) began. The men read some magazines or newspapers that contained no sexually stimulating material for 1.5 h. There was no interaction between the men and observer during the test period. Times to first measured and total durations of base and tip rigidities, and also total and per minute rigidity were evaluated.. The recorded base and/or tip rigidity ratios were 40% (eight of 20), 71% (12/17), 47% (nine of 19) and 70% (14/20) in men who took placebo, sildenafil, tadalafil and vardenafil, respectively (P = 0.126). The ratio of men who could obtain ≥ 60% base and/or tip rigidities were 10% (two of 20), 41% (seven of 17), 26% (five of 19) and 55% (11/20) in placebo, sildenafil, tadalafil and vardenafil groups, respectively (P < 0.05). The median time to first measured base rigidity was 58.0, 21.5, 54.5 and 57 min with placebo, sildenafil, tadalafil and vardenafil, respectively (P = 0032). The median total duration of recorded base rigidity was 4.0, 27.5, 10.0 and 11.5 min in men who took placebo, sildenafil, tadalafil and vardenafil, respectively (P = 0.013). The median total base rigidity (area under the curve) was 72.8, 699.0, 360.5 and 553.0 with placebo, sildenafil, tadalafil and vardenafil, respectively (P = 0.016).. Significant penile rigidities were obtained with PDE5 inhibitors during the short test period, with no sexual stimulation, in laboratory conditions. This finding might support the use of PDE5 inhibitors in men who need penile rehabilitation.

Topics: Adolescent; Adult; Carbolines; Double-Blind Method; Ejaculation; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Penile Erection; Phosphodiesterase 5 Inhibitors; Photic Stimulation; Piperazines; Purines; Quality of Life; Sexual Behavior; Sildenafil Citrate; Sulfones; Tadalafil; Time Factors; Triazines; Vardenafil Dihydrochloride; Young Adult

Diabetic neuropathy (DN) is one of the key pathogenetic factors for diabetic erectile dysfunction (DED).. The aim of this study was to compare the effect of the first intake of tadalafil and vardenafil in men with DN and DED.. In this comparative prospective randomized study were included 49 phosphodiesterase type 5 (PDE5) inhibitor-naïve men (80% type 2 diabetes). DN was assessed by a modified Neuropathy Disability Score (NDS ≥ 3). Each patient received two pills containing 20 mg of either tadalafil (N = 24) or vardenafil (N = 25). They had to be taken after discharge from the hospital at a time interval of at least 3 and 1 day, respectively, and 1 to 6 hours before the intended sexual activity.. The treatment efficacy was evaluated by the changes in the erectile domain of International Index of Erectile Function (IIEF), Sexual Encounter Profile Question 2 (SEP2) and 3 (SEP3), and the Global Assessment Question (GAQ).. For all patients, IIEF increased from 12.6 ± 6.8 to 19.6 ± 9.0 (P < 0.001) points after treatment. The number of men with positive answers on SEP2 increased from 27 (55.1%) to 38 (77.6%), on SEP3 from 7 (14.3%) to 30 (61.2%). Thirty-one (63.3%) evaluated the effect of the drugs as beneficial (GAQ). No significant efficacy difference between tadalafil and vardenafil was observed. The initial indicators for DED, as well as the treatment efficacy, correlated highly significant with NDS. Both PDE5 inhibitors were well tolerated. Before entering the study, 28% of men have seen a physician, but only 57.1% of them have started treatment.. In this study design, tadalafil and vardenafil are equally effective with the first intake in patients with diabetes and DN. Baseline indicators of erectile dysfunction and the ones verifying the effect of the treatment show significant correlation with the DN indicator-NDS. Tadalafil and vardenafil are well tolerated with no serious side effects.

Topics: Age Factors; Carbolines; Diabetic Neuropathies; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Risk Factors; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To investigate the impact of penile surgery on the erectile function of the patient and to evaluate the role of small-dose vardenafil in restoring the impaired penile erection.. Sixty cases of penile cavernosum surgery were equally and randomly divided into a vardenafil and a control group, the former treated 5 - 7 days after surgery with 10 mg vardenafil every other day, while the latter given vitamin E at 100 mg once a day, both for 12 weeks. The penile erectile function of the patients was evaluated with the IIEF-5 questionnaire before surgery and at 3 and 6 months after vardenafil medication.. The mean IIEF-5 scores of the vardenafil group were 18.83 +/- 2.98 and 20.13 +/- 2.98 at 3 and 6 months after vardenafil medication, significantly higher than 14.21 +/- 3.62 before surgery (P > 0.05), while that of the control group was significantly decreased at 3 months as compared with the preoperative score (13.38 +/- 2.82 versus 15.80 +/- 3.02, P < 0.05). The vardenafil group showed the highest IIEF-5 score after surgery (P < 0.05).. Long-term administration of small-dose vardenafil after penile surgery helps to restore and maintain penile erectile function.

Topics: Adult; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Penile Erection; Penis; Piperazines; Postoperative Period; Recovery of Function; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Erectile dysfunction (ED) impacts on both members of the couple. Female partners of men with ED are more likely to report reduced sexual quality of life than women whose partners do not have ED.. To assess vardenafil efficacy in men with ED and determine the effects of treatment on their female partner's sexual quality of life.. Study participants comprised men aged 18-64 years with ED and their female partners. Eligible men had ED of ≥6 months' duration and a female partner who was motivated to support their ED treatment. Eligible women had a total Female Sexual Function Index score >23.55, indicating absence of significant sexual dysfunction. Following a 4-week screening period, men were randomized to treatment with vardenafil 10 mg or placebo, which could be titrated to 20 or 5 mg after 4 weeks.. Primary efficacy variables were question 3 of the Sexual Encounter Profile questionnaire (SEP3) and the quality-of-life domain of the modified Sexual Life Quality Questionnaire (mSLQQ-QOL).. The intent-to-treat population included 343 couples, with 168 and 175 men receiving vardenafil or placebo, respectively. Vardenafil treatment significantly improved both erection maintenance and the female partners' sexual quality of life. Least squares (LS) mean SEP3 overall success rates after 12 weeks of treatment were 9.5 (baseline) vs. 67.2 (week 12) and 12.4 (baseline) vs. 24.2 (week 12) in the vardenafil and placebo groups, respectively (P < 0.0001). In female partners, LS mean mSLQQ-QOL scores were 28.8 (baseline) vs. 68.2 (last observation carried forward [LOCF]) in the vardenafil group and 24.6 (baseline) vs. 40.5 (LOCF) in the placebo group (P < 0.0001).. Vardenafil treatment of men with ED improved both their erectile function and the sexual quality of life of their female partners.

Topics: Adult; Aged; Double-Blind Method; Erectile Dysfunction; Female; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Quality of Life; Sexual Behavior; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Young Adult

The prevalence of erectile dysfunction (ED) is increased in men with metabolic syndrome compared with the general population.. The aim of this study was to evaluate the efficacy and safety of vardenafil vs. placebo in men who had ED and metabolic syndrome.. This was a 12-week, double-blind, randomized, multicenter, parallel-group, placebo-controlled prospective study in men with ED and metabolic syndrome (assessed by the International Diabetes Federation criteria). Vardenafil was administered at a starting dose of 10 mg, which could be titrated to 5 mg or 20 mg after 4 weeks, depending on efficacy and tolerability.. Primary efficacy measures were the erectile function domain of the International Index of Erectile Function (IIEF-EF) and Sexual Encounter Profile (SEP) diary questions 2/3. Secondary efficacy measures included SEP1, a diary question assessing ejaculation, the percentage of men achieving "return-to-normal" erectile function, and the percentage of men who titrated to a different dose. Adverse events (AEs) were recorded throughout the study.. The intent-to-treat population included 145 men (vardenafil, N = 75; placebo, N = 70). Baseline least squares IIEF-EF domain scores were low (vardenafil: 12.0; placebo: 12.7), indicative of moderate-to-severe ED. Vardenafil was statistically significantly superior to placebo for all primary efficacy measures (P < 0.0001) and showed nominally statistically significant superiority compared with placebo for SEP1/ejaculation success rates (P = 0.0003 and P < 0.0001, respectively) and the percentage of subjects reporting "return-to-normal" erectile function (P = 0.0004). Treatment-emergent AEs were mild-to-moderate in severity and consistent with the known AE profile of phosphodiesterase type 5 inhibitors.. This is the first study to assess the efficacy and safety of vardenafil, taken alone, for ED therapy in a population of men who all had metabolic syndrome. Although baseline erectile function in these patients was low, vardenafil treatment was associated with significant improvements in erectile function and rates of successful intercourse, and was well tolerated.

Topics: Adult; Aged; Erectile Dysfunction; Humans; Imidazoles; Male; Metabolic Syndrome; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Patients and physicians consider a rapid onset of action to be an important attribute of oral pharmacotherapy for erectile dysfunction.. To investigate the time to onset of action of a new orodispersible tablet (ODT) formulation of vardenafil.. A post hoc integrated analysis was performed on data from two 12-week, double-blind, multicenter, randomized, parallel-group, placebo-controlled phase III trials of 10 mg vardenafil ODT. Data for the vardenafil film-coated tablet were generated from a retrospective integrated analysis at week 12 of four double-blind, multicenter, randomized, parallel-group, fixed-dose, placebo-controlled phase III trials. Time intervals (in 15-, 30-, and 60-minute increments, up to ≥6 hours after study medication intake) were determined for the period between dosing and start of sexual activity (with the intention of intercourse).. The total number of sexual intercourse attempts and Sexual Encounter Profile question 3 (SEP3) success rates were calculated per time interval.. Within 15 minutes postdosing, mean per-patient SEP3 success rates were 62.5% (vardenafil ODT) vs. 29.4% (placebo), with corresponding overall SEP3 success rates of 59.8% and 38.2%. In this time interval, 5.3% vs. 2.8% of all sexual activity attempts were initiated by subjects taking vardenafil ODT (n = 89) or placebo (n = 62), respectively. At 16-30 minutes postdosing, SEP3 success rates were 65.3% and 32.6% (mean per-patient) and 70.2% and 51.0% (overall) for vardenafil ODT vs. placebo, respectively, with a corresponding 10.4% and 8.7% of all sexual activity attempts being made by subjects taking vardenafil ODT (n = 170) or placebo (n = 118). Comparable results were observed for vardenafil 10 and 20 mg film-coated tablet at corresponding time intervals.. Vardenafil ODT shows a rapid onset of action comparable with that of vardenafil film-coated tablet. In those men who begin sexual activity within 30 minutes after dosing, the majority of sexual attempts lead to successful intercourse.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Delayed-Action Preparations; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Retrospective Studies; Sexual Behavior; Sulfones; Tablets; Time Factors; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Young Adult

Although the Sexual Encounter Profile (SEP) and International Index of Erectile Function (IIEF) are frequently used to measure erectile dysfunction (ED) treatment outcomes, stopwatch-assessed duration of erection is a new, objective, and potentially useful endpoint of ED treatment effect.. To assess the validity and reliability of stopwatch-assessed erection duration against responses to SEP items 2 (SEP-2) and 3 (SEP-3) and IIEF scale scores.. Data were taken from a multi-center trial of vardenafil for the treatment of ED. Patients were randomized to vardenafil 10 mg or placebo for 4 weeks. After a 1-week washout period, patients received the alternate therapy for an additional 4 weeks. An electronic diary was used to record information about sexual attempts. The duration of erection was measured using a stopwatch and transcribed into the diary. The SEP was completed following each sexual attempt, and the IIEF was completed at the end of each treatment period.. Mean and median values of erection duration, mean SEP-2 and SEP-3 success rates, and scores for each of the 5 IIEF scales were calculated.. At baseline, correlations of median erection duration with the 5 IIEF scale scores ranged from 0.06 to 0.53, while correlations with mean SEP-2 and SEP-3 success rates were 0.66 and 0.49, respectively. Compared with the other measures, mean and median values of erection duration were less sensitive to differences between placebo- and vardenafil-treated patients and less responsive to clinical change associated with treatment crossover. However, mean erection duration exhibited a good level of reliability (intraclass correlation coefficient = 0.72, P < 0.001).. This study provides evidence for the validity and reliability of stopwatch-assessed duration of erection. Our findings suggest that erection duration is suitable for use as a unique endpoint in ED treatment-efficacy trials conducted for phosphodiesterase type 5 inhibitors.

Topics: Erectile Dysfunction; Humans; Imidazoles; International Cooperation; Interpersonal Relations; Male; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Reference Values; Severity of Illness Index; Sexual Behavior; Sulfones; Surveys and Questionnaires; Time Factors; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Orodispersible tablet (ODT) formulations offer improved convenience over film-coated formulations and are preferred by many patients.. To investigate the efficacy and safety of an ODT formulation of 10 mg vardenafil administered on demand vs. placebo in a general population of men with erectile dysfunction (ED).. This was a 16-week, double-blind, multicenter, randomized, parallel-group, placebo-controlled study conducted at 40 centers across Europe and South Africa. Eligible participants were men aged > or = 18 years with ED for at least 6 months, in a stable heterosexual relationship for at least 6 months, highly motivated to obtain ED treatment, and making at least four attempts at sexual intercourse on four separate days, of which at least half were unsuccessful. Subjects were randomized to receive 12 weeks of treatment with either 10 mg vardenafil ODT on demand or placebo, and each treatment group was stratified such that approximately half of the subjects were aged > or = 65 years.. Primary measures were the erectile function domain of the International Index of Erectile Function (IIEF-EF) and the Sexual Encounter Profile questions 2 and 3 (SEP2, SEP3). Secondary measures included SEP diary questions 1, 4, 5, and 6; the Treatment Satisfaction Scale; and the Global Assessment Question.. Of the 409 men enrolled (54.8% aged > or = 65 years), 355 were included in the intent-to-treat population (vardenafil ODT, N = 183; placebo, N = 172). Vardenafil ODT therapy was statistically significantly superior to placebo for all primary (IIEF-EF, SEP2, SEP3) and secondary efficacy measures (all P < 0.0001). The incidence and type of treatment-related adverse events with vardenafil 10 mg ODT were comparable with those of the film-coated tablet formulation.. Treatment with 10 mg vardenafil ODT, taken on demand, significantly improved erectile function and was well tolerated in a broad population of men with ED.

Topics: Administration, Oral; Adult; Aged; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Penile Erection; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Tablets; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Long-acting injectable testosterone undecanoate (TU, Nebido(®)), a new parenteral testosterone preparation, has recently been introduced to avoid frequent injections of the conventional injectable esters.. To assess the efficacy and safety of long-acting injectable testosterone undecanoate (TU, Nebido(®)) in Korean patients with testosterone deficiency syndrome (TDS).. One hundred thirty-three patients who complain of erectile dysfunction with serum testosterone level less than 3.5 ng/mL were injected with 1,000 mg of TU (4 mL/ample) on day 1, followed by another injection after 6 weeks and 18 weeks. For the safety profiles, serum hemoglobin (Hb), hematocrit (Hct), glucose, lipid profile, and prostate-specific antigen (PSA) were measured.. Body mass index (BMI) was measured at the time of the first visit and after 12, 24 weeks. Primary efficacy was evaluated according to changes in the International Index of Erectile Function (IIEF) from the initial visit to the final visit (24 weeks) and from the initial visit to each visit. Secondary efficacy was assessed with changes of the Aging Males' Symptoms (AMS) Scale and the Global Efficacy Question (GEQ) for improvement of erectile function.. Mean age of patients was 54 ± 9.6 years. Compared with pretreatment, no significant improvement in BMI was observed. Serum total testosterone and free testosterone were significantly increased at 12 weeks and were maintained until 24 weeks (P < 0.001). TU significantly decreased cholesterol (P < 0.0001). TU significantly improved total IIEF, all five domain scores of IIEF (P < 0.0001) and total AMS, all three domain scores of AMS (P < 0.0001). On GEQ, TU improved erectile function in 76.9% of subjects. On safety profile, TU significantly elevated Hb, Hct, and PSA at 24 weeks but within normal range. No serious adverse reactions were observed. Drop-out rate was 15.0%.. In this prospective multicenter study, TU was effective, safe, and tolerable until 24 weeks in Korean TDS patients. Further well-controlled, long-term study should follow.

Topics: Adult; Aged; Androgens; Cross-Cultural Comparison; Delayed-Action Preparations; Drug Administration Schedule; Drug Therapy, Combination; Erectile Dysfunction; Humans; Hypogonadism; Imidazoles; Korea; Male; Middle Aged; Penile Erection; Phosphodiesterase 5 Inhibitors; Piperazines; Prospective Studies; Sulfones; Testosterone; Triazines; Vardenafil Dihydrochloride

The aim of this study was to investigate the efficacy and safety of 10 mg vardenafil orodispersible tablet (ODT) vs. placebo in a general population of men with erectile dysfunction (ED).. This was a double-blind, multicentre, randomised, parallel-group, placebo-controlled study conducted at 35 centres in Australia, Canada, Mexico and the United States. Subjects aged > or =18 years, with ED for at least 6 months, were randomised to receive 12 weeks of on-demand treatment with either 10 mg vardenafil ODT or placebo. Each treatment group was stratified such that approximately half of the subjects were aged > or = 65 years. Primary efficacy variables were the erectile function domain of the International Index of Erectile Function (IIEF-EF) and Sexual Encounter Profile questions 2 (SEP2) and 3 (SEP3). Secondary variables included SEP diary questions 1, 4, 5 and 6, the patient version of the Treatment Satisfaction Scale (TSS) and the Global Assessment Question (GAQ).. Of the 473 men enrolled in the study (51.4% aged > or =65 years), 331 were included in the intent-to-treat population (vardenafil ODT, n = 169; placebo, n = 162). Vardenafil ODT therapy was statistically significantly superior to placebo for all primary (i.e. IIEF-EF, SEP2, SEP3) and secondary efficacy variables (p < 0.0001). Treatment-emergent adverse events were mostly mild to moderate in severity, and comparable in both incidence and type with those of the film-coated tablet formulation.. Treatment with 10 mg vardenafil ODT, taken on demand, significantly improved erectile function and was effective and well tolerated in a broad population of men with ED.

Topics: Administration, Oral; Adult; Aged; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Tablets; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) is prevalent in end-stage renal disease (ESRD) and has been associated with impaired health-related quality of life (HRQoL). HRQoL, in turn, is related to morbidity and mortality in ESRD patients. Previous studies have shown improved HRQoL with ED treatment using sildenafil and vardenafil. However, no study has examined the effects of sildenafil or vardenafil on HRQoL in impotent ESRD patients. Furthermore, vardenafil has never been tested and its safety profile has not been determined in ESRD patients. The aim of this randomized crossover study was to compare the effects of sildenafil and vardenafil on measures of HRQoL and on ED scores as well as to determine the safety profile of vardenafil in ESRD patients.. In 32 haemodialysis patients with impotence, ED and HRQoL were evaluated by the International Index of Erectile Function (IIEF-5) and the 36-item Short-Form Health (SF-36) surveys, respectively. Patients were randomized into sildenafil and vardenafil groups. After a 4-week treatment and 2-week washout periods, crossover was performed and an additional 4-week treatment was administered. IIEF-5 and SF-36 surveys were given before and after each treatment period. Adverse effects were evaluated by interview. Friedman tests and Bonferroni-adjusted Wilcoxon signed-rank tests were used to compare groups and for post hoc analysis, respectively.. IIEF-5 and SF-36 scores were significantly improved by both sildenafil and vardenafil compared to pretreatment values. There were no differences between sildenafil and vardenafil with respect to the studied parameters. Adverse effect profiles were also similar. No patient dropped out because of side effects.. Sildenafil and vardenafil caused similar improvements in ED and HRQoL in haemodialysis patients. Vardenafil was well tolerated in our patient population.

Topics: Adult; Aged; Cross-Over Studies; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Prospective Studies; Purines; Quality of Life; Renal Dialysis; Sildenafil Citrate; Sulfones; Triazines; Vardenafil Dihydrochloride; Young Adult

Topics: Adolescent; Adult; Blood Pressure; Cross-Over Studies; Cyclohexanes; Erectile Dysfunction; HIV Fusion Inhibitors; HIV Infections; Humans; Imidazoles; Male; Maraviroc; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Single-Blind Method; Sulfones; Triazines; Triazoles; Vardenafil Dihydrochloride; Vasodilator Agents; Young Adult

To study the clinical efficacy of vardenafil on erectile dysfunction (ED) patients with kidney-yang deficiency, kidney-yin deficiency or liver-qi stasis.. Based on the syndromes of Traditional Chinese Medicine, 124 ED patients were divided into Groups A (kidney-yang deficiency, n=44), B (kidney-yin deficiency, n=41) and C (liver-qi stasis, n = 39). All the patients were treated with vardenafil at 5 mg daily for 8 weeks, and the therapeutic effects were evaluated by comparing the scores on IIEF-5 and Erection Quality Scale (EQS) before and after the treatment.. After vardenafil treatment, the IIEF-5 and EQS scores of the ED patients were markedly increased, with statistically significant differences among the three groups (P < 0.01). The success rate of sexual intercourse was significantly improved in Groups A, B (P < 0.01) and C (P < 0.05). And the hardness of penile erection was enhanced by 81.82%, 73.17% and 43.59% respectively in the three groups of patients.. Vardenafil is more effective for ED patients with kidney-yang or kidney-yin deficiency than for those with liver-qi stasis.

Topics: Adult; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents; Yang Deficiency; Yin Deficiency

The ENDURANCE study evaluated the efficacy of vardenafil, a phosphodiesterase type 5 (PDE5) inhibitor, in men with erectile dysfunction (ED), by measuring the duration of erection leading to successful intercourse using a stopwatch as the assessment instrument.. This was a randomised, multicentre, double-blind, placebo-controlled, crossover study consisting of a 4-week treatment-free run-in phase after which patients were randomised to either fixed-dose vardenafil 10 mg or placebo (to be administered 60 min prior to intercourse) and entered the first of the two 4-week double-blind treatment periods, separated by a 1-week washout. The primary efficacy end-point was the stopwatch-assessed duration of erection, which was defined as the time from erection perceived hard enough for penetration until withdrawal from the partner's vagina leading to successful intercourse as measured by Sexual Encounter Profile Question 3 (SEP-3). Secondary efficacy end-points included SEP-2 and SEP-3 success rates, the erectile function domain of the International Index of Erectile Function, global assessment questionnaire, change from baseline in duration of erection and duration of erection not leading to successful intercourse. Safety was assessed by adverse events (AEs), laboratory samples, vital signs and ECGs.. Of the 191 men included in the safety population, 40% had moderate ED and 33% had severe ED at baseline. The duration of erection (least squares mean +/- SE) leading to successful intercourse was longer with vardenafil than with placebo (12.81 +/- 1.00 min vs. 5.45 +/- 1.00 min; p < 0.001). The differences recorded for all secondary end-points were statistically significant in favour of vardenafil compared with placebo (p < 0.001), with the exception of duration of erection not leading to successful intercourse. Vardenafil was well tolerated in this study; the majority of AEs being mild-to-moderate in intensity.. Vardenafil 10-mg therapy provided a statistically superior duration of erection leading to successful intercourse in men with ED compared with placebo.

Topics: Adult; Coitus; Cross-Over Studies; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Severity of Illness Index; Sulfones; Surveys and Questionnaires; Time Factors; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Young Adult

The efficacy and safety of two types of phoshodiestrase type 5 ( PDE 5) inhibitors (sildenafil (sil) and vardenafil (var)) were investigated for multi-centric study.. One hundred and twenty five patients (55.9 +/- 10.9 years old) with erectile dysfunction (ED) were treated by both of sil and var. The patients were administered a pair of 25 mg of sil and 5 mg of var, or 50 mg of sil and 10 mg of var. The efficacy for ED and safety of these 2 drugs were evaluated after administration of each drugs at least 2 times.. The results showed that the score of international index of erectile function 5 (IIEF5) were elevated from 8.87 +/- 4.10 to 17.24 +/- 6.17 after treatments (p< 0.0001, Student' s t test). The efficacy rates for ED were 81.6% in sil and 81.6% in var, respectively. The adverse reactions rates such as headache, burning, palpitation, etc. were 13.6% in sil and 5.6% in var, which is significantly higher in sil (p = 0.032; chi2 test). These side effects were not serious at all, and there were no cases that gave up to use PDE5 inhibitors because of adverse reactions. According to individual patients experiences, 40.7% of patients preferred sil, 45.4% choose var. In addition, associated effects for quality of life (QOL) of ED patients treated by PDE5 inhibitors were analyzed. The results revealed that encouraging in life 46.5%, rejuvenation feeling 45.1%, self care for their health 28.2%, improvement of depression 12.7%, improvement of voiding dysfunction 5.6%, intimacy with partner 38.0%, good conversation with partner 18.3%, and so on.. The treatments of ED by sil and var were very effective and safety. Furthermore, associated effects for QOL of ED patients were also improved with these treatments.

Topics: Adult; Aged; Erectile Dysfunction; Humans; Imidazoles; Japan; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

We investigated safety and efficacy of vardenafil and sertraline in premature ejaculation (PE). Seventy-two men graded their primary PE on a scale of 0-8 (0 = almost never, 8 = almost always). Intravaginal ejaculatory latency time (IELT) was measured. Patients were included if they scored their PE as 4 or greater and their IELTs were less than 1.30 min. After 6 weeks of behavioural psychosexual therapy, 49 patients still had a PE of 4 or greater and an IELT less than 1.30 min and they were randomised: 6 weeks vardenafil (10 mg) or sertraline (50 mg). After a wash-out phase for 1 week, medication was changed in a cross-over design. Initially, all 72 men with PE received behavioural therapy. Twenty-three men were satisfied with treatment and excluded. The remaining 49 men graded their PE as 5.94 +/- 1.6 and IELT was 0.59 min and patients were randomised. Four men discontinued the study. Vardenafil improved PE grading: 2.7 +/- 2.1 (P < 0.01) and IELT increased to 5.01 +/- 3.69 (P < 0.001). PE grading improved 1.92 +/- 1.32, (P < 0.01) and IELT 3.12 +/- 1.89 (P < 0.001) with sertraline. It is concluded that vardenafil and sertraline are useful agents in the pharmacological treatment of PE.

Topics: Adult; Behavior Therapy; Cross-Over Studies; Ejaculation; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Piperazines; Safety; Sertraline; Sexual Dysfunctions, Psychological; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

The association of diabetes-related vascular damage and the role of metabolic factors in erectile dysfunction are well known in the literature. The compounds propionyl-L-carnitine (PLC), L-arginine (L-Arg) and nicotinic acid have numerous metabolic actions which have been reported to improve endothelial function. This study investigated the administration of the combination of these three compounds alone and in association with an inhibitor of 5-phosphodiesterase (5PDE), vardenafil, on endothelial function in diabetic patients with erectile dysfunction.. A total of 40 patients aged between 50 and 60 years with insulin-dependent diabetes (IDDM) for 3-4 years were selected from 509 patients presenting with erectile dysfunction. The patients were randomly subdivided into four groups of ten to be treated for 12 weeks. Group A was administered one sachet each day of test formulation containing PLC, L-Arg and nicotinic acid (Ezerex); group B with one 20 mg capsule of vardenafil (Levitra) twice a week; group C was treated with one sachet each day of the test formulation plus vardenafil 20 mg twice a week. Group D was administered placebo capsules twice weekly. Endothelial function was evaluated by examining flow-mediated dilation (FMD) and erectile function was estimated with the International Index of Erectile Function (IIEF5) questionnaire in all subjects.. At the end of treatment group A showed an increment of 2 points in the IIEF5; group B showed an increment of 4 points; group C, the group which was administered all the treatments, showed an increment of 5 points, and group D, treated with placebo, showed no increment in the IIEF5.. Although there was a small number of subjects in this study the data suggest that the test formulation may improve the endothelial situation in diabetes. The test formulation together with vardenafil was better than the 5PDE inhibitor alone, but further studies are needed to confirm these findings.

Topics: Arginine; Carnitine; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Niacin; Penile Erection; Piperazines; Placebos; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Vardenafil is reported to improve success rates in the maintenance of an erection sufficient for completion of intercourse (SEP-3) compared with placebo in erectile dysfunction (ED) patients who attempted intercourse from as early as 15 minutes after dosing. However, these data were based on general ED patients, using time from administration to initiation of intercourse. It is unclear whether the results can be applied to difficult-to-treat ED patients, such as those with diabetes mellitus (DM), with the time between dosing and insertion into vagina.. To determine whether early onset of activity with vardenafil is also achievable in ED patients with DM.. Data from a 12-week Phase III clinical trial (randomized, placebo-controlled, double-blind, parallel-group comparison) in Japanese men with ED and DM was used for analysis. In this study, patients received vardenafil 10 mg, 20 mg, or placebo, and were instructed to start sexual activity 1 hour after dosing. Mean per-patient SEP-3 success rates (intent-to-treat; ITT population), based on patient diary question, were calculated by the time between dosing and insertion. The least-squares means and nominal P values for differences versus placebo were derived by analysis of covariance with terms for baseline.. SEP-3 success rates in each time interval.. The majority of inserts occurred between 60-90 minutes after dosing, but 100 of inserts in 52 patients occurred in the first 30 minutes. SEP-3 success rates in patients who inserted in each interval from 0-15 minutes (P = 0.0268), 15-30 minutes (P = 0.0094) through > 120 minutes were all higher in vardenafil-treated patients than those in placebo.. In this retrospective analysis, a rapid onset of activity was also demonstrated in difficult-to-treat ED patients. Vardenafil improved successful intercourse rates compared with placebo in Japanese DM patients who inserted from as early as 15 minutes to >120 minutes after dosing.

Topics: Adult; Coitus; Diabetes Complications; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Japan; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Retrospective Studies; Sulfones; Time Factors; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents; Young Adult

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).. To evaluate if platelet cyclic guanosine monophosphate (cGMP) could represent a valuable marker for PDE5-I activity in ED.. 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.. All patients donated two blood samples, one before starting the protocol and the second after 6 wk of treatment.. 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.. Platelet cGMP production was significantly (p<0.05) elevated in patients taking 5mg 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.. 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.

Topics: Adult; Aged; Biomarkers; Blood Platelets; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Dose-Response Relationship, Drug; Drug Monitoring; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Placebos; Reproducibility of Results; Sulfones; Triazines; Vardenafil Dihydrochloride; Young Adult

We investigated the effect of the combination of the doxazosin gastrointestinal therapeutic system and 10 mg vardenafil on the hemodynamic status of patients with benign prostatic hyperplasia and erectile dysfunction.. This was a double-blinded, randomized, placebo controlled crossover trial. Patients with benign prostatic hyperplasia and erectile dysfunction treated with the doxazosin gastrointestinal therapeutic system on a regular basis, with no other antihypertensive events, were recruited. Subjects took 10 mg vardenafil or placebo in a randomized crossover fashion with a washout period of at least 7 days between each treatment. The supine and standing blood pressure of the subjects was recorded from 1 hour before to 6 hours after the administration of vardenafil or placebo. The primary outcome of the study was the maximal change in standing systolic blood pressure of the subjects from 1 half hour before to 6 hours after the administration of drugs.. A total of 37 patients, 25 (67.6%) and 12 (32.4%) on the doxazosin gastrointestinal therapeutic system at 4 mg and 8 mg, respectively, completed the trial. The combination drug therapy resulted in a maximal decrease in standing systolic blood pressure of 6.18 mm Hg (95% CI -12.02, -0.33; p = 0.039). Only 1 patient had an asymptomatic standing systolic blood pressure of less than 85 mm Hg. Otherwise no symptomatic hypotension or clinically significant adverse cardiovascular event was observed during the study.. In patients on the doxazosin gastrointestinal therapeutic system for benign prostatic hyperplasia a single 10 mg dose of vardenafil had no symptomatic hemodynamic effects.

Topics: Adrenergic alpha-Antagonists; Aged; Analysis of Variance; Blood Pressure; Cross-Over Studies; Double-Blind Method; Doxazosin; Drug Therapy, Combination; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Placebos; Prostatic Hyperplasia; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

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).. 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.. 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 > or =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.. Patients received placebo, nightly vardenafil, or on demand vardenafil.. Primary outcome measure was the percentage of subjects with an IIEF-EF score of > or =22 after the 2-mo washout period. Secondary variables included mean per-patient success rates for Sexual Encounter Profile (SEP) questions 2 and 3.. No statistically significant differences were observed among treatment groups in the proportion of patients with an IIEF-EF score of > or =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.. 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.. European clinical trials database (EudraCT; available at http://eudract.emea.europa.eu/).. 11336.

Topics: Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prostate; Prostatectomy; Recovery of Function; Sulfones; Triazines; Vardenafil Dihydrochloride

To evaluate the efficacy and safety of vardenafil in kidney transplant recipients with erectile dysfunction.. Thirty-nine kidney transplant recipients with erectile dysfunction (ED) and serum creatinine values <2 mg/dl were enrolled in a 4-week randomized, double blind, placebo-controlled study, 19 treated with placebo and 20 with vardenafil. Vardenafil efficacy was assessed with the IIEF questionnaire after 4 weeks of treatment, and its safety appraised by measuring serum creatinine levels, creatinine clearances and cyclosporine concentrations before and after the treatment.. IIEF scores improved from 12.6 +/- 3.4 to 26.5 +/- 2.8 (P < 0.01), but renal function and cyclosporine concentrations remained unchanged in the vardenafil-treated patients. Adverse effects were observed in 4 patients: headache in 2, palpitation and flush in 1, and dyspepsia in the other.. Oral vardenafil therapy has a high efficacy and a low incidence of adverse events for kidney transplant recipients with ED.

Topics: Adult; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Kidney Transplantation; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Renal Dialysis; Sulfones; Triazines; Vardenafil Dihydrochloride

To study effects of different treatments on erectile and endothelial functions in patients with erectile dysfunction (ED) and age-related hypogonadism (HG).. The study included 66 males with ED who had clinical and laboratory signs of HG. All the patients were examined using questionnaires (international index of erectile function, AMS), blood hormones tests. Endothelial function was assessed with postcompression tests on the cavernous arteries and blood homocystein assay. All the patients were divided into two matched groups. Group 1 (20 males, mean age 54.6 +/- 11.5 years) received androgens only, replacement therapy consisted of testosterone undecanoate (Nebido, Shering) 1000 mg each 10-12 weeks intramuscularly, interval between the first and second injection was 6 weeks. Group 2 (46 males, mean age 53.98 +/- 10.03 years) was given combined treatment (androgens and PDE 5 inhibitors), wardenafil (Levitra, Buer Shering Pharma) was used in a dose 20 mg. The treatment lasted 6 months.. AMS points decreased in group 1 from 38.3 +/- 0.29 to 29.2 +/- 0.32, in group 2--from 39.02 +/- 0.21 to 28.6 +/- 0.95, while testosterone rose from 9.86 +/- 0.4 to 17.77 +/- 0.42 and 9.35 +/- 0.25 to 17.21 +/- 0.63 nmol, respectively. Homocystein lowering was significantly more manifest in group 2. EF index in group 2 rose from 11.4 +/- 0.77 to 25.54 +/- 0.25 points versus 11.2 +/- 1.01 to 23.95 +/- 0.71 points in group 1, improvement of EF in group 2 occurred sooner. Endothelial function by diameter of the cavernous arteries differed after treatment in group 1 and 2 (19.55 +/- 2.88 to 39.2 +/- 0.84% and 19.51 +/- 1.28 to 48.5 +/- 1.76, respectively, p<0.001).. Combined therapy improves blood homocistein, acts faster and stronger on endothelial and erectile functions and can be recommended as first line for ED and HG patients.

Topics: Drug Therapy, Combination; Endothelium, Vascular; Erectile Dysfunction; Homocysteine; Humans; Hypogonadism; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Risk Factors; Sulfones; Testosterone; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Phosphodiesterase type 5 inhibitors are the first choice therapy in the treatment of erectile dysfunction. Many men in their reproductive years are now using phosphodiesterase type 5 inhibitors. The purpose of this study was to determine the effects of 6 months of treatment with 20 mg vardenafil, compared with 100 mg sildenafil and placebo, on semen characteristics and reproductive hormones in men with and without erectile dysfunction.. This was a randomized, double-blind, placebo controlled, parallel group, multicenter study. A total of 200 men with or without erectile dysfunction, able to produce semen samples without erectile dysfunction therapy, 25 to 64 years old, were randomized to daily treatment with vardenafil, sildenafil or placebo for 6 months. The primary variable was the percentage of vardenafil treated individuals with a 50% or greater decrease in mean sperm concentration from baseline to 6-month last observation carried forward, compared with placebo treated individuals.. The between group difference (vardenafil minus placebo) in the percentage of patients with 50% or greater decrease in sperm concentration (baseline to 6 months last observation carried forward) was 0.07% (95% CI, -8.53% to 8.39%). Vardenafil also had no clinically significant effects on any other semen parameters, or on levels of reproductive hormones, when compared with placebo. Similar data were observed with sildenafil.. This study demonstrated that vardenafil had no adverse effects on sperm concentration, compared with sildenafil and placebo, when administered daily at the maximum recommended dose for 6 months. Specifically, use of vardenafil for 6 months does not impair sperm concentration, total sperm count per ejaculate, or sperm morphology and motility. Levels of reproductive hormones were also unaffected.

Topics: Adult; Double-Blind Method; Erectile Dysfunction; Gonadal Hormones; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Semen; Sildenafil Citrate; Sperm Count; Sulfones; Triazines; Vardenafil Dihydrochloride

Studies evaluating the effect of education on treatment success with phosphodiesterase type 5 (PDE5) inhibitor therapy in men with erectile dysfunction (ED) are limited. Additional education of the primary care physician (PCP) and the patient are thought to optimize the treatment of ED.. To assess the impact of education of the PCP or of the patient in the treatment of ED with vardenafil relative to usual care.. In this 12-week, open-label, multicenter, factorial-designed, cluster-randomized Canadian study, 1,029 patients with ED were enrolled into four different education groups: usual care, patient education, PCP education, and both PCP and patient education. All groups started on vardenafil 10 mg, with the option to titrate at weeks 4 and 8.. The primary efficacy measure was the difference at week 4 last observation carried forward (LOCF) in the overall improvement in erectile function (EF) as measured by the Global Assessment Question (GAQ), while on background vardenafil, between those receiving education vs. those who did not. Other secondary assessments included responses to diary questions regarding penetration (sexual encounter profile, SEP2) and erection maintenance (SEP3), and to questionnaires regarding treatment satisfaction (Erectile Dysfunction Inventory of Treatment Satisfaction [EDITS]).. A total of 956 patients were included in the intent-to-treat population. Mean baseline International Index of Erectile Function-EF domain score was 13. GAQ response rates at week 4 LOCF were high (>80%) for all groups, regardless of the education given. Mean per patient SEP2 and SEP3 rates at week 12 LOCF were 86-89% and 79-83%, respectively. In an exploratory analysis, a positive relationship between GAQ responses and EDITS scores was observed (P < or = 0.0007). Vardenafil was generally well tolerated.. In men with moderate ED, vardenafil led to high success rates and satisfaction regardless of the education given. The benefits of education for PCP and patients in Canada were possibly masked by a ceiling effect in this study population.

Topics: Adult; Canada; Combined Modality Therapy; Counseling; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Education as Topic; Personal Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Primary Health Care; Professional-Patient Relations; Quality of Life; Sulfones; Triazines; Vardenafil Dihydrochloride

The aim of this study was to evaluate the safety and efficacy of vardenafil in outpatients with chronic schizophrenia and erectile dysfunction and to investigate any effect on quality of life in this population.. In this 12-week, open-label, flexible-dose study, 25 outpatients with chronic schizophrenia (DSM-IV criteria) and erectile dysfunction received vardenafil 10 mg as needed (at a maximum of 1 dose per day) with the option to maintain current dose or to titrate to 5 mg or 20 mg at 4 and 8 weeks. Assessment was performed with the International Index of Erectile Function (IIEF) at base line and at weeks 4, 8, and 12. The Quality of Life Scale (QLS) was administered at baseline and at week 12. The study was carried out at the Psychiatric Hospital of Athens, Greece, between October 2005 and November 2006.. Vardenafil produced a statistically significant improvement in all IIEF domains [erectile function (p < .001), orgasmic function (p < .05), sexual desire (p < .05), intercourse satisfaction (p < .01), and overall satisfaction (p < .001)] and QLS (p < .003). Results were similar for the intention-to-treat (N = 25) and completer (N = 21, 84%) groups. Adverse events were infrequent and decreased in incidence over the course of the study.. Vardenafil was generally well tolerated and highly effective in outpatients with chronic schizophrenia and erectile dysfunction. The response to vardenafil was not influenced by certain patient characteristics, such as erectile dysfunction severity or serum prolactin levels. Improvement in sexual function was correlated with improvement in the quality of life.

Topics: Adult; Aged; Analysis of Variance; Chronic Disease; Drug Administration Schedule; Erectile Dysfunction; Greece; Humans; Imidazoles; Male; Middle Aged; Orgasm; Outpatients; Patient Satisfaction; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Prolactin; Prospective Studies; Quality of Life; Research Design; Schizophrenia; Sulfones; Time Factors; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Phosphodiesterase type-5 (PDE-5) inhibitors have previously been evaluated for their efficacy and safety in various clinical trials in men with erectile dysfunction (ED) with or without associated comorbidities.. This is the first prospective, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a PDE-5 inhibitor (i.e., vardenafil) in an exclusive population of men with ED and dyslipidemia.. Three coprimary efficacy measurements (Sexual Encounter Performance [SEP]2, SEP3, International Index of Erectile Function-Erectile Function [IIEF-EF] domain scores) were used to assess the differential effect of vardenafil vs. placebo in this patient population. Adverse events (AEs) safety data were obtained to compare safety outcomes.. This 12-week of randomized, double-blind, placebo-controlled study was conducted in 59 U.S. centers. Patients received either on-demand, flexible-dose vardenafil 10 mg (titrated to 5 mg or 20 mg based upon efficacy and safety) or placebo.. Of the 712 patients screened and entered into the study, 395 were randomized. Baseline demographics for the intent-to-treat population included: mean age, 54.4 years (+/-7.5 standard deviation [SD]); 76% Caucasian; mean body mass index (BMI), 31.7 kg/m(2) (+/-12.7 SD); 47% past/present smoker; and 42% severe ED. Aside from dyslipidemia, other comorbidities included hypertension, 61%; obesity (i.e., BMI >/= 30), 51%; and type 1 or 2 diabetes, 40%. During the 12-week treatment period, the least squares (LS) adjusted mean success rates in patients on vardenafil vs. placebo were: SEP2, 79.09% vs. 51.92%; and SEP3, 66.69% vs. 33.83% (P < 0.001). The LS adjusted mean IIEF-EF domain score for week 12 using LOCF was 21.99 in patients on vardenafil therapy vs. 14.83 in those on placebo (P < 0.001). The most commonly encountered AEs were headache and nasal congestion.. Vardenafil was demonstrated to be safe and effective for managing ED in men with ED and associated dyslipidemia. The results of this study support the role of expanded research on outcomes related to effective ED treatment and aggressive lipid control.

Topics: Coitus; Diabetes Mellitus; Double-Blind Method; Dyslipidemias; Erectile Dysfunction; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Sulfones; Treatment Outcome; Triazines; United States; Vardenafil Dihydrochloride

Multicenter, double-blind, placebo-controlled, parallel-group study.. To assess the effect of the oral phosphodiesterase type-5 inhibitor, vardenafil, on ejaculation rates and self-confidence in men with spinal cord injury (SCI).. Spinal command of male sexual functions is often seriously impaired by traumatic spinal cord injury (SCI). A high proportion of men with SCI cannot ejaculate during sexual intercourse. SCI-related ejaculatory disorders are often responsible for male infertility. Sexual dysfunction associated with SCI can also affect men's self-confidence.. In this 12-week study, 418 men aged >or=18 years with erectile dysfunction >6 months resulting from a traumatic SCI were randomized to vardenafil (n = 207) or placebo (n = 211) 10 mg for 4 weeks, then maintained or titrated to 5 or 20 mg at weeks 4 and 8. Assessments included questions of the International Index of Erectile Function (IIEF) about ejaculation success and orgasmic perception; the Global Confidence Question; and quality-of-life scales to measure psychological well-being, self-esteem, depression, and mental health status.. Overall per patient ejaculation success rates were significantly greater with vardenafil than placebo over 12 weeks of treatment (19% vs. 10%; P < 0.001). At last observation carried forward, the IIEF "orgasmic function" score increased from 2.9 at baseline to 4.0 for vardenafil and from 3.0 at baseline to 3.4 for placebo. Sixteen percent of men receiving vardenafil and 8% receiving placebo felt orgasm "almost always" or "always" at weeks 8-12, compared with 4% and 6%, respectively, at baseline. Significant improvements in confidence scores were observed with vardenafil compared with placebo (P < 0.0001). There were no clinically significant differences between vardenafil and placebo in the quality-of-life measures at the study endpoint, but these had been in the normal range at baseline.. Vardenafil significantly improved ejaculation and self-confidence in men with erectile dysfunction due to SCI.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Coitus; Double-Blind Method; Ejaculation; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Quality of Life; Spinal Cord Injuries; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To evaluate the efficacy and tolerability of vardenafil, a phosphodiesterase type-5 (PDE-5) inhibitor, in men of Asian ethnicity with erectile dysfunction (ED).. 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.. 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.. 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.

Topics: Adult; Aged; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Sulfones; Triazines; Vardenafil Dihydrochloride

Phosphodiesterase (type) 5 (PDE5) inhibitors are currently administered on demand for treatment of erectile dysfunction (ED). Once-daily dosing has been suggested to benefit patients.. To determine whether daily vardenafil use provides added clinical benefits to patients compared with on-demand dosing.. In this placebo-controlled, double-blind, multicentre parallel-group study, men with mild-to-moderate ED were randomised to 24 wk of treatment, followed by a 4-wk washout.. Patients were randomised to receive once-daily vardenafil 10mg plus on-demand placebo for 12 or 24 wk, or once-daily placebo plus on-demand vardenafil 10mg for 24 wk.. Primary efficacy variable was the between-group difference in change in International Index of Erectile Function-Erectile Function domain (IIEF-EF) score from baseline to end of washout. Secondary variables included change from baseline in proportion of positive respondents to Sexual Encounter Profile questions and in satisfaction with treatment as assessed with the Treatment Satisfaction Scale (TSS).. LS mean changes from baseline in IIEF-EF scores were 2.02, 2.29, and 2.63 for vardenafil 12 wk once daily, 24 wk once daily, and 24 wk on demand, respectively. After washout, the trend was towards improved IIEF-EF scores in the on-demand group (20.58 [+/-0.96]) versus both once-daily groups (12 wk, 19.88 [+/-0.93]; 24 wk, 20.11 [+/-0.94]). Furthermore, there were no significant between-group differences in the percentage of patients with "normal" erectile function. TSS analyses demonstrated no significant differences between treatment groups. This study recruited patients with mild-to-moderate ED; therefore, the results may not be the same as in patients with severe ED.. Once-daily vardenafil did not produce greater sustained effects on EF than on-demand vardenafil in men with mild-to-moderate ED, suggesting that daily dosing of PDE5 inhibitors does not produce sustained clinical benefits beyond cessation of treatment above those observed with on-demand administration.

Topics: Double-Blind Method; Drug Administration Schedule; Erectile Dysfunction; Germany; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Open, before-after study.. To assess the efficacy and safety of phosphodiesterase type 5 (PDE5) inhibitors for erectile dysfunction (ED) in spinal cord-injured (SCI) patients.. Home- and clinic-based assessments in the outpatient department at the Centre Bouffard Vercelli, Cerbère France.. Clinic trials with Sildenafil (Viagra) on 120 patients, Tadalafil (Cialis) on 54 patients and Vardenafil (Levitra) on 66 patients were performed. Flexible doses of PDE5 inhibitors were given depending on efficacy and tolerability, from 50 to 100 mg for Sildenafil, and from 10 to 20 mg for Vardenafil and Tadalafil. Each trial was performed after a week's interval. The efficacy was self-assessed by the patients on a six-point quantitative scale assessment. The response to treatment was assessed at home in 90 patients (57 patients on Sildenafil, 12 patients on Vardenafil and 21 patients on Tadalafil) using the International Index of Erectile Function (IIEF).. In clinic trials, PDE5 inhibitors were effective (rigidity enough for penetration) in 85% of the patients on Sildenafil, 74% of the patients on Vardenafil and 72% of the patients on Tadalafil. The mean duration of erection was 34, 28 and 26 min, respectively. Adverse effects were mild, usually attenuated with continued dosing. More than 70% of the patients on Vardenafil and Tadalafil required higher doses of 20 mg, whereas 50 mg of Sildenafil was effective in 55% of the patients. Two-thirds of our patients on Tadalafil reported a duration of action longer than 24 h. The presence of an upper motor neuron lesion was significantly associated with therapeutic success, lower motor neuron lesions and cauda equina patients were poor responders. Other variables such as completeness of lesion had no impact. In the follow-up visits, the IIEF global scores and three IIEF domains (erectile function, intercourse satisfaction and overall satisfaction) were significantly improved in all patients. Patients on Sildenafil showed a significant improvement of orgasmic function, ejaculation (Question 9) and orgasm (Question 10).. Sildenafil, Vardenafil and Tadalafil are all effective and well-tolerated treatments for ED in SCI patients. Although no statistical analysis could be applied on these data, these results might indicate that Sildenafil is more effective in treating ED. Clinic trials are important for proper dose titration and appropriate education of the patients.

Topics: Adult; Analysis of Variance; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Reaction Time; Retrospective Studies; Sildenafil Citrate; Spinal Cord Injuries; Sulfones; Surveys and Questionnaires; Tadalafil; Triazines; Vardenafil Dihydrochloride

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.. 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).. 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.. 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.

Topics: Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Purines; Remission Induction; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Tadalafil; Time Factors; Triazines; Vardenafil Dihydrochloride

Clinical trials show that vardenafil produces effective and satisfactory first-dose success rates and reliability for erection and intercourse in men with erectile dysfunction (ED).. This study was conducted to evaluate real-life efficacy, safety, and acceptance of vardenafil in men with ED.. This open-label, prospective study, conducted in 6,740 U.S. centers, included an initial visit and one or two follow-up visits within a 2-month period of the first vardenafil dose. Vardenafil was administered in 5-20 mg doses.. Efficacy variables included first-dose success rates for vaginal penetration, maintenance of erection, and satisfaction based on physician and patient assessments. Safety was assessed by adverse events (AEs).. A total of 30,010 men were included in the safety/intent-to-treat (S/ITT) analysis, with 26,043 men in the adjusted S/ITT population. Vardenafil improved erectile function in 78% of men, with 75% rating overall efficacy as "satisfying" or "very satisfying." The overall rates of successful penetration and maintenance with vardenafil following the first dose were 78% and 68%, respectively. For men with mild and moderate ED, first-dose success rates for penetration were 89% and 82%, respectively, and for maintenance, 82% and 71%, respectively. First-dose penetration and maintenance of erection rates were 76% and 66%, respectively, for men with self-reported hypertension, and 70% and 60%, respectively, for men with diabetes mellitus. At study end, 67% of patients preferred to continue using vardenafil. The most frequently reported AEs were headache (4%) and flushing (2%). Vardenafil was well tolerated, with a "satisfied/very satisfied" tolerability rating in 75% of cases as assessed by the physician.. This observational study demonstrated the tolerability and efficacy of vardenafil in men with ED and comorbidities. Vardenafil provided a high rate of first-dose intercourse success and a favorable safety profile in patients with and without comorbid disease.

Topics: Adult; Aged; Coitus; Dose-Response Relationship, Drug; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Quality of Life; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; United States; Vardenafil Dihydrochloride

To assess the efficacy of vardenafil in a population of Spanish men with erectile dysfunction (ED), its influence on patients' self-esteem and self-confidence, and its effect on their quality of life.. Efficacy was assessed by the International Index of Erectile Function-Erectile Function (IIEF-EF) domain, the Rosenberg Self-Esteem scale, the Johnson and McCoy Self-Confidence scale, the Medical Outcome Short Form (SF-36) scale, items 2 and 3 of the Sexual Encounter Profile questionnaire, and the Global Assessment Question (GAQ). Safety assessments included laboratory tests, physical exam, electrocardiogram, vital signs, and adverse events.. This was a randomized, double-blind, multicenter, placebo-controlled study. After a 4-week treatment-free period, patients received flexible-dose vardenafil or placebo for 12 weeks. The initial dose was 10 mg, which could be titrated up to 20 mg or down to 5 mg at weeks 4 and 8.. A total of 121 patients were included in the intention-to-treat analysis (61 on vardenafil and 60 on placebo). Of these, 16 in the vardenafil group and 14 in the placebo group had severe ED. There was a greater improvement in IIEF-EF domain score with vardenafil vs. placebo for all patients (score change of 10.9 vs. 1.6, respectively, P < 0.001) and for patients with severe ED (score change of 13.4 vs. 2.2, respectively, P = 0.011). A significant difference in favor of vardenafil was also observed for positive responses to the GAQ (73.8% vs. 25.0%, P < 0.001). After 12 weeks, vardenafil-treated patients with severe ED showed a significant improvement in their self-esteem compared with patients receiving placebo (change from baseline -1.51 vs. 3.54, respectively, P = 0.036). Vardenafil treatment was well tolerated.. Vardenafil was highly effective for improving EF in all patients with ED, and resulted in significant improvements in self-esteem in patients with severe ED.

Topics: Adult; Aged; Coitus; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Quality of Life; Self Concept; Severity of Illness Index; Spain; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

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.. 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.. 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.. 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.

Topics: Aged; Analysis of Variance; Double-Blind Method; Erectile Dysfunction; Female; Humans; Imidazoles; Logistic Models; Male; Middle Aged; Patient Satisfaction; Penile Erection; Personal Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Quality of Life; Sexual Partners; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Previous clinical studies assessing the efficacy and safety of vardenafil, an oral phosphodiesterase type 5 inhibitor, in men with erectile dysfunction (ED) have consisted mostly of Caucasian patients.. The aim of this article is to describe the efficacy and safety of vardenafil in men of East Asian ethnicity with ED.. Data were pooled from two 12-week, double-blind studies that included 306 East Asian men randomized to placebo or 10 mg of vardenafil.. Efficacy variables included the International Index of Erectile Function-erectile function (IIEF-EF) domain score, questionnaires of Sexual Encounter Profile (SEP2 and SEP3), and a Global Assessment Question (GAQ). Safety assessments included laboratory tests, vital signs, 12-lead electrocardiogram recordings, and patients' reporting of adverse events.. A total of 306 East Asian men with ED were treated with placebo (N = 151) or vardenafil (N = 155). Mean baseline IIEF-EF domain scores (placebo, 13.4; vardenafil, 14.2) were consistent with moderate ED. At end point, the patients treated with vardenafil had a significantly greater increase in IIEF-EF domain score compared with placebo (24.2 vs. 15.9; P < 0.0001). The average per patient penetration (SEP2) success rate was significantly higher in the vardenafil group compared with placebo (88% vs. 58%; P < 0.0001). Moreover, the average per patient intercourse completion (SEP3) success rate was significantly higher in the vardenafil group compared with placebo (69% vs. 23%; P < 0.0001). Positive GAQ responses were reported by 85% of patients receiving vardenafil, compared with 33% of those receiving placebo. The most frequent adverse events were vasodilatation (primarily facial flushing), rhinitis, and headache, all of which were of mild intensity.. Vardenafil is an effective, well-tolerated oral drug for the treatment of East Asian men with moderate ED of broad-spectrum etiology.

Topics: Adult; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Erectile Dysfunction; Humans; Imidazoles; Korea; Male; Middle Aged; Patient Satisfaction; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Research Design; Severity of Illness Index; Sulfones; Taiwan; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

To evaluate the effects of Huafenqinutang combined with vardenafil for the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with erectile dysfunction.. One hundred and thirty-eight cases diagnosed as CP/CPPS with erectile dysfunction were randomized into trial group (70 cases) and control group (68 cases) for treatment with Huafenqinutang for 8 weeks, and in the former group, vardenaffil was added since the fifth weeks. All the cases were evaluated according to NIH-CPSI and IIEF-5 scores at 4 weeks and 8 weeks, respectively.. At the end of the fourth weeks, NIH-CPSI score was 13.1-/+4.7 in the trial group and 13.3-/+4.5 in the control group, which were comparable between the two groups (P>0.05) but significantly decreased compared with the pre-treatment scores in both groups (P<0.01). IIEF-5 score was also similar between the two groups (14.1-/+3.3 vs 14.3-/+5.0, P>0.05) but significantly increased compared with the pre-treatment scores in both groups (P<0.01). At the end of the eighth week, NIH-CPSI score was 7.8-/+2.2 and IIEF-5 score 20.1-/+4.4 in the trial group, which were significantly different from those at the end of the fourth week (P<0.01). In the control group, NIH-CPSI score was 12.7-/+2.3 and IIEF-5 score 14.3-/+4.5 at the eighth week, similar to those at the end of the fourth week (P>0.05). There were significant differences in NIH-CPSI and IIEF-5 scores between the 2 groups (P<0.01), and the change of NIH-CPSI score was negatively correlated with IIEF-5 score in the trial group (r=-0.89, P<0.01).. For patients with CP/CPPS with erectile dysfunction, Huafenqinutang treatment in combination with vardenafil can effectively improve the erectile functions and decrease the NIH-CPSI score to favor the recovery from CP/CPPS.

Topics: Adult; Drugs, Chinese Herbal; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Pelvic Pain; Phytotherapy; Piperazines; Prostatitis; Sulfones; Triazines; Vardenafil Dihydrochloride

The aim of this study was to investigate the effects of vardenafil on systemic blood pressure, intraocular pressure (IOP), and orbital hemodynamics.. Twenty-one (21) volunteers suffering erectile dysfunction, with an average age of 51.5 +/- 6.2 years, were enrolled into the study. Brachial blood pressures and IOP were measured, the peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) of the ophthalmic, central retinal, and posterior ciliary arteries were evaluated by color Doppler ultrasonography (CDU) before vardenafil intake. All measurements were repeated after 20 min of vardenafil intake. A paired Student t test was used to evaluate the changes.. Systolic blood pressure did not change significantly where diastolic blood pressure decreased significantly (P = 0.043) after drug ingestion. There was no significant change in IOP. Increase in EDV of CRA was significant (P = 0.04), but the increase of orbital blood flow velocities of OA and PCA were insignificant.. The recommended dose of vardenafil has no negative effects on orbital hemodynamics and IOP in patients with erectile dysfunction.

Topics: Blood Flow Velocity; Blood Pressure; Ciliary Arteries; Erectile Dysfunction; Humans; Imidazoles; Intraocular Pressure; Male; Middle Aged; Ophthalmic Artery; Phosphodiesterase Inhibitors; Piperazines; Retinal Artery; Sulfones; Triazines; Ultrasonography, Doppler, Color; Vardenafil Dihydrochloride; Vasodilator Agents; Visual Acuity

Erectile dysfunction (ED) treatment studies do not routinely measure "treatment effectiveness," a function of treatment response (based on efficacy and tolerability) and treatment satisfaction (both patient and partner satisfaction). The ED Treatment Satisfaction Scale (TSS) is a brief, comprehensive self-report measure of patient and partner satisfaction.. To measure, for the first time in an ED treatment study, pre- and post-treatment patient and partner satisfaction with the TSS.. A randomized, double-blind, placebo-controlled, parallel-group, multi-institutional comparison of the efficacy and safety of flexible-dose vardenafil was performed in 229 couples (treated man with ED >6 months and untreated woman partner aged > or =18 years without sexual dysfunction [defined as a total Female Sexual Function Index score >26.55]).. Couples completed the TSS throughout the trial. Couples also completed the modified Sexual Life Quality Questionnaire-Quality of Life domain (mSLQQ-QoL) and men completed the International Index of Erectile Function-erectile function domain (IIEF-EF). Analysis of covariance produced least squares (LS) mean domain scores. Post hoc Pearson correlation coefficients were calculated for patient and partner TSS scores, and for TSS scores with other outcomes.. TSS domain scores increased from baseline to last observation carried forward (LOCF) in the vardenafil-treated men and untreated women partners, but exhibited little change for the placebo group (P < 0.0001 vs. placebo). For both patients and partners in the vardenafil group, correlations between TSS domains, the IIEF-EF and the mSLQQ-QoL scores at LOCF were moderate to strong.. The TSS detected that vardenafil was superior to placebo on treatment satisfaction from both patient and partner perspectives. The TSS holds promise for evaluating "treatment effectiveness" by measuring more general treatment satisfaction.

Topics: Adult; Aged; Dose-Response Relationship, Drug; Erectile Dysfunction; Female; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Personal Satisfaction; Piperazines; Quality of Life; Research Design; Sexual Behavior; Sexual Partners; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

To evaluate the efficacy and safety of sertraline and vardenafil in the treatment of patients with concomitant erectile dysfunction (ED) and premature ejaculation (PE).. Sixty patients with concomitant ED and PE received at our clinic of andrology were randomly divided into a vardenafil group and a sertraline group. The vardenafil group received flexible doses of vardenafil from 10 mg to 20 mg and the sertraline group 50 mg daily, both for 2 months. The differences in IIEF-5 before and after the treatment were recorded and compared, and the results of ED treatment evaluated. Intravaginal ejaculatory latency time (IELT) was recorded to evaluate the outcome of PE treatment.. In the vardenafil group, 24 patients had their ED improved and the efficacy rate was 80%, as compared with 27% in the sertraline group. There was significant difference between the two groups (P < 0.05). Twenty patients had their PE improved in vardenafil group, with an efficacy rate of 67% as compared with 40% in the sertraline group. The difference was significant between the two groups (P < 0.05). In both of the two groups, a significantly higher rate of PE improvement was found in patients with improved ED than in those without. Only mild side effects were recorded, and none withdrew from the treatment.. To patients with concomitant ED and PE, the key to the treatment is to improve their erectile function, and for this purpose, vardenafil works better than sertraline.

Topics: Adult; Ejaculation; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Selective Serotonin Reuptake Inhibitors; Sertraline; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

We evaluated the responsiveness and treatment sensitivity of the Erection Quality Scale, and provided further psychometric validation of this scale.. An 8-week, placebo controlled, randomized clinical trial investigating the efficacy and safety of vardenafil in patients with erectile dysfunction was performed. The Erection Quality Scale, together with a number of other patient and partner questionnaires, was administered at a screening visit, at baseline, and weeks 4 and 8 of treatment. Erection Quality Scale responsiveness was investigated by evaluating treatment induced changes and modeling using ANCOVA. Internal consistency, convergent and discriminant validity, and minimum important difference of the Erection Quality Scale were also assessed.. Efficacy evaluations demonstrated that the Erection Quality Scale was sufficiently responsive to differentiate the treatment benefits of vardenafil compared with placebo. Internal consistency for the Erection Quality Scale total score was similar across visits, with values high enough to suggest reliability of items included in the scale. Discriminant validity of the Erection Quality Scale total score was demonstrated, with a high correlation with the erectile function domain of the International Index of Erectile Function (0.88, p <0.0001) and negligible correlations with clinical measures assumed to be unrelated to erection quality. All Erection Quality Scale total score comparisons substantially exceeded the 5-point minimum important difference estimate.. The Erection Quality Scale was responsive and internally consistent, and demonstrated convergent and discriminant validity. Furthermore, this instrument provided a unique contribution to the measurement of erection quality compared to the International Index of Erectile Function. This study provides strong evidence supporting the use of the Erection Quality Scale in clinical trials.

Topics: Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Follow-Up Studies; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

We assessed urodynamic changes after vardenafil administration in spinal cord injured male patients on oxybutynin treatment.. We performed a single center, randomized, double-blind, placebo controlled trial in 25 patients with spinal cord injury who had erectile dysfunction and micturition disorders. A baseline urodynamic test was performed as well as a second urodynamic test 1 to 3 hours after the administration of 20 mg vardenafil and placebo in 15 and 10 cases, respectively. In all patients standard oral oxybutynin administration was not discontinued. Statistical assessment included the 3 urodynamic parameters maximum detrusor pressure during voiding, maximum cystometric capacity and detrusor overactivity volume.. Placebo administration did not affect urodynamic parameters. After vardenafil administration maximum detrusor pressure was significantly decreased (59.3 vs 52.1 cm H(2)O, p <0.001) and maximum cystometric capacity considerably improved (233.5 vs 272 ml, p <0.001). The most dramatic variations were observed for detrusor overactivity volume (174 vs 218 ml, p <0.0001). In 7 patients with American Spinal Injury Association classification A and spinal cord injury above T6 we observed the most significant improvement in the evaluated urodynamic items, including maximum detrusor pressure 57 vs 52 cm H(2)O (p = 0.039), maximum cystometric capacity 253 vs 296 ml (p = 0.004) and detrusor overactivity volume 177 vs 229 ml (p = 0.003).. This trial demonstrates that in spinal cord injured patients a single 20 mg vardenafil administration achieved a significant decrease in maximum detrusor pressure, an improvement in maximum cystometric capacity and a remarkable increase in detrusor overactivity volume value.

Topics: Administration, Oral; Adult; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Follow-Up Studies; Humans; Imidazoles; Male; Mandelic Acids; Middle Aged; Parasympatholytics; Phosphodiesterase Inhibitors; Pilot Projects; Piperazines; Retrospective Studies; Spinal Cord Injuries; Sulfones; Treatment Outcome; Triazines; Urination Disorders; Urodynamics; Vardenafil Dihydrochloride

Erectile dysfunction and depression are highly associated. Previous studies have shown benefits of phosphodiesterase-5 inhibitor treatment for erectile dysfunction associated with antidepressant therapy or subsyndromal depression. The present study assessed the safety and efficacy of vardenafil in men with erectile dysfunction and untreated mild depression.. In this 12-week, multicenter, randomized, flexible-dose, parallel-group, double-blind study, 280 men with erectile dysfunction for at least 6 months and untreated mild major depression received placebo or vardenafil, 10 mg/day, for 4 weeks, with the option to titrate to 5 mg/day or 20 mg/day after each of two consecutive 4-week intervals. Endpoints included International Index of Erectile Function erectile function domain and 17-item Hamilton Depression Rating Scale (HAM-D) scores.. Vardenafil produced statistically significant and clinically meaningful improvement in all erectile function parameters. The International Index of Erectile Function erectile function domain score was 22.9 with vardenafil compared to 14.9 with placebo. The HAM-D score was lower in the vardenafil group (7.9) than in the placebo group (10.1). Treatment with vardenafil was the most important predictor for return to normal erectile function. Improvement in International Index of Erectile Function erectile function domain score was the most important predictor of remission in depressive symptoms.. Vardenafil was well tolerated and highly efficacious in men with erectile dysfunction and untreated mild major depression. Significant improvements in erectile function and depression were observed in patients treated with vardenafil versus placebo. Erectile dysfunction treatment should be considered a component of therapy for men with depression and erectile dysfunction.

Topics: Comorbidity; Depressive Disorder, Major; Double-Blind Method; Drug Administration Schedule; Erectile Dysfunction; Humans; Imidazoles; Least-Squares Analysis; Male; Middle Aged; Phosphoric Diester Hydrolases; Piperazines; Placebos; Psychiatric Status Rating Scales; Severity of Illness Index; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To assess the efficacy and tolerability of vardenafil in men with erectile dysfunction (ED) due to traumatic spinal cord injury (SCI).. In this multicenter, double-blind, placebo-controlled, parallel-group 12-week study, 418 men aged 18 years and older with ED for more than 6 months consequent to SCI were randomized to vardenafil (n = 207) or placebo (n = 211) (10 mg for 4 weeks, then maintained or titrated to 5 or 20 mg at weeks 4 and 8). Efficacy assessments included the erectile function (EF) domain score of the International Index of Erectile Function questionnaire and diary questions regarding penetration, maintenance of erection to completion of intercourse, and ejaculation.. Baseline patient characteristics were similar in the vardenafil (mean age 40 years) and placebo (mean age 39 years) groups. Mean baseline EF domain scores were 11.6 in the vardenafil group and 12.1 (moderate ED) in the placebo group. EF domain score in the vardenafil group improved to 22.0 (mild ED) at last observation carried forward vs 13.5 in the placebo group (p < 0.001). Over 12 weeks of treatment, mean per-patient penetration (76% vs 41%), maintenance (59% vs 22%), and ejaculation (19% vs 10%) success rates were significantly greater vs placebo (all p < 0.001). The most frequently reported drug-related adverse events were headache (vardenafil 15%, placebo 4%), flushing (vardenafil 6%, placebo 0%), nasal congestion (vardenafil 5%, placebo 0%), and dyspepsia (vardenafil 4%, placebo 0%).. Vardenafil significantly improved erectile and ejaculatory function and was generally well tolerated in men with erectile dysfunction due to spinal cord injury.

Topics: Adult; Coitus; Double-Blind Method; Dyspepsia; Ejaculation; Erectile Dysfunction; Flushing; Headache; Humans; Imidazoles; Male; Medical Records; Nasal Obstruction; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Spinal Cord Injuries; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) profoundly affects the quality of life. The prevalence of ED in renal transplant recipients is reported by high as 50% to 60%. We evaluated the efficacy and safety of vardenafil in these patients with ED as well as its effects on graft function and on cylosporine or tacrolimus concentrations. Thirty-nine recipients with ED and serum creatinine values<2 mg/dL were treated with vardenafil. ED was assessed using the self-administered International Index of Erectile Function (IIEF). ED was diagnosed by using penile color-Doppler ultrasonography and intracavernosal injection. Vardenafil efficacy was assessed by readministering the IIEF questionnaire after 4 weeks of therapy. Serum creatinine levels, creatinine clearances, and cyclosporine/tacrolimus concentrations were measured before and after vardenafil therapy. Twenty-one recipients with ED served as placebo controls and 15 without ED as another control group. The IIEF scores improved from 12.80+/-3.5 to 26.46+/-2.4 in vardenafil-treated patients with ED (P<.001). Renal function and cyclosporine/tacrolimus concentrations did not change with vardenafil therapy. Side effects were observed in 7 (18%) patients: headache in three, palpitations in one, flushing in two, and dyspepsia in one. This study demonstrated that ED improved with vardenafil in renal transplant recipients with ED. For 4 weeks vardenafil therapy was free of side effects. Renal function tests did not change. Also, no dose change in immunosuppressive drugs was required during 4 weeks of verdanafil therapy.

Topics: Adult; Creatinine; Erectile Dysfunction; Humans; Imidazoles; Kidney Transplantation; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Postoperative Complications; Prospective Studies; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

This study explored the efficacy of vardenafil in men with erectile dysfunction (ED) when taken 8 hours before sexual intercourse.. A 10-week, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study of vardenafil (5, 10 or 20mg) was conducted in men with ED for >6 months who failed >or=50% of intercourse attempts during a 4-week treatment-free run-in period. Sexual Encounter Profile Question 3 (SEP3) was the primary efficacy measure; secondary measures included SEP2, International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, Global Assessment Question (GAQ), Global Confidence Question (GCQ) and Erection Quality Scale (EQS). Adverse-event and safety monitoring were conducted throughout.. 383 patients were randomized to vardenafil (n=194) or placebo (n=189). Patients treated with vardenafil 8 hours before sexual activity achieved clinically meaningful (>or=18%) and statistically significantly greater least-squares mean per-patient SEP3 and SEP2 success rates over weeks 2-10, compared with patients receiving placebo (SEP3 69% vs 34%; SEP2 81% vs 51%; both p<0.001). SEP3 and SEP2 measures demonstrated the significant superiority of vardenafil over placebo from week 2 onwards (p<0.001). Measurements of IIEF-EF domain score, GAQ, GCQ and EQS showed that vardenafil led to significantly greater improvements in erectile function, compared with placebo (all p<0.001). Vardenafil was generally well tolerated.. The extended duration of efficacy of vardenafil up to 8 hours postdose may provide couples with more flexibility in their sexual life than anticipated.

Topics: Adult; Aged; Coitus; Double-Blind Method; Drug Administration Schedule; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Piperazines; Sulfones; Time Factors; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Vardenafil is a highly selective and potent phosphodiesterase type-5 inhibitor for the treatment of erectile dysfunction (ED). The efficacy of vardenafil has been demonstrated in a broad range of ED populations, but has not yet been assessed in Japanese patients with diabetes mellitus (DM), although DM is frequently associated with difficult-to-treat ED. This is the first study to investigate whether high-dose vardenafil (20 mg) can demonstrate superior efficacy to the usual dose (10 mg) in this subpopulation in Japan.. The study was a randomized, placebo-controlled, double-blind, multi-centre, parallel group comparison 12-week study. Following 4 weeks observation period, 778 patients aged 26-64 years old with ED and DM (HbA1c >12% at screening was excluded) both of more than 3 years duration were randomly allocated to one of the three groups, vardenafil 10 mg, 20 mg, or placebo (randomization ratio 3:3:1). Erectile function (EF) domain score of the International Index of Erectile Function was estimated as the primary efficacy parameter.. Vardenafil 10 and 20 mg both significantly improved the EF domain score from 13.6 and 13.9 at baseline to 21.8 and 22.9 at last observation carried forward (LOCF), respectively, compared to placebo (13.7 at baseline to 16.3 at LOCF; p<0.0001). In addition, vardenafil 20 mg demonstrated superior efficacy to 10 mg (p<0.05), and the difference was more evident in severe ED patients (baseline EF domain score <11). The safety profile was comparable between these two doses (drug-related adverse events: 6.6, 22.0 and 24.2% in placebo, vardenafil 10 mg, and 20 mg arms, respectively). The most common adverse events were hot flush, headache and nasal congestion, which were mild in intensity and transient, and are known to be common to PDE5 inhibitors.. In Japanese men with DM and ED, vardenafil 10 mg and 20 mg were effective in improving erectile function with comparable safety profiles. Vardenafil 20 mg demonstrated superior efficacy compared with 10 mg, suggesting incremental clinical benefit in using the higher dose in this difficult-to-treat population.

Topics: Adult; Diabetes Complications; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Japan; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To prospectively investigate whether vardenafil can effectively treat patients for whom sildenafil (100 mg) has failed. The introduction of two new oral phosphodiesterase type 5 inhibitors (tadalafil and vardenafil) raises the question of whether the new agents will permit us to treat sildenafil nonresponders with another oral agent.. Patients were seen at one institution during a 5-year period. A total of 327 patients complaining of sildenafil-refractory erectile dysfunction underwent intracavernous pharmacologic injection and color duplex Doppler ultrasonography. Subsequently 59 of these men tried vardenafil home dosing.. Of the 327 men in whom sildenafil failed, 16% were younger than 50, 21% were 51 to 60, 34% were 61 to 70, and 28% were older than 70 years. The Doppler diagnoses were arterial insufficiency in 154 (47%), mixed vascular insufficiency in 73 (22%), and cavernous venous occlusive disease in 57 (17%). Forty-three men (13%) had normal erectile responses to prostaglandin E1 (10 to 20 microg). Of the 59 men who tried vardenafil, 19% were younger than 50, 17% were 51 to 60, 40% were 61 to 70, and 23% were older than 70 years. The Doppler diagnoses were arterial insufficiency in 28 (42%), mixed vascular insufficiency in 10 (19%), and cavernous venous occlusive disease in 15 (29%). Six men (8%) had normal erectile responses to prostaglandin E1. Only 7 (12%) of the 59 men reported that home vardenafil dosing resulted in successful intercourse.. An appropriate diagnostic evaluation and subsequent treatment algorithm have yet to be established for those for whom phosphodiesterase type 5 inhibitors fail. We found that most sildenafil nonresponders had severe arterial insufficiency and were older, with 62% older than 60 years. Our preliminary experience suggests that only a small percentage (12%) of sildenafil nonresponders can be salvaged with vardenafil.

Topics: Adult; Aged; Aged, 80 and over; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Purines; Sildenafil Citrate; Sulfones; Treatment Failure; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) affects up to 70% of men with diabetes, occurring with a higher prevalence in those with type 1 diabetes than with type 2 diabetes. Studies investigating treatment of ED in men with diabetes have largely been conducted in a total male population with diabetes. Limited data are available on the efficacy and safety of the potent oral phosphodiesterase-5 inhibitor vardenafil in men with ED and type 1 diabetes.. To evaluate the safety and efficacy of flexible-dose vardenafil therapy in a prospective randomized study in phosphodiesterase 5 inhibitor-naïve subjects with type 1 diabetes and ED.. In this multicenter, double-blind, placebo-controlled clinical trial, phosphodiesterase-5 inhibitor-naïve patients were randomized to receive placebo (N = 149) or flexible-dose (5-20 mg) (N = 153) vardenafil.. Sexual Encounter Profile diary questions 2 and 3, concerning success rates of vaginal insertion and maintenance of erection to allow successful intercourse, respectively.. Vardenafil significantly improved mean success rates for Sexual Encounter Profile 2 and 3 compared with baseline and placebo at 4, 8, and 12 weeks (P < 0.0001, intention to treat and last observation carried forward). These rates were unaffected by stratification into distinct subsets according to the level of HbA(1c) (HbA(1c) < 7%, good glycemic control; HbA(1c) >7- < or = 8%, moderate glycemic control; and HbA(1c) > 8%, poor glycemic control). Vardenafil treatment also significantly improved the Erectile Function domain score (P < 0.0001) of the International Index of Erectile Function compared with placebo, in addition to scores for the other individual domains of the International Index of Erectile Function. The most commonly reported treatment-emergent adverse events were headache (3.1%) and flushing (2.5%), which were mild to moderate and transient in nature.. These data suggest that vardenafil significantly improves erectile function in men with type 1 diabetes and is well tolerated, regardless of the level of glycemic control.

Topics: Adult; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Quality of Life; Sexual Behavior; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Phosphodiesterase type 5 inhibitor drugs produce vasodilatation by inhibiting the breakdown of cyclic guanosine monophosphate and have proven efficacy in treating erectile dysfunction (ED).. To evaluate the efficacy, safety, and tolerability of vardenafil in men with moderate to severe ED of broad etiology.. The erectile function (EF) domain score, the response to Questions 13 and 14 of the International Index of Erectile Function (IIEF) questionnaire, and the proportion of "yes" responses to questions 2 and 3 of the Sexual Encounter Profile (SEP), a Global Assessment (GAQ), and Global Satisfaction Questions (GSQ) were compared at baseline and at 12 weeks of treatment with as-needed vardenafil.. A total of 326 subjects with a mean age of 57.6 years and moderate to severe erectile dysfunction of various etiologies received vardenafil (5-20 mg) for 12 weeks in a prospective multicenter, open-label flexible-dose study.. Compared with baseline, vardenafil was superior in all efficacy outcomes. A significant mean improvement of 13.4 (P < 0.001) in the EF domain from baseline was obtained at week 12. Subjects who received 5, 10, and 20 mg vardenafil at week 12 experienced improvements of 11.9, 15.1, and 12.9 respectively in the EF domain score. Sexual intercourse was successfully completed (SEP3) in 76.3%, 80.1%, and 74.3% of subjects receiving 5, 10, and 20 mg vardenafil compared with 25.9%, 17.9%, and 19.2% at baseline, respectively. For all doses combined at week 12, the change in SEP3 from baseline was 56.7% (P < 0.001). Treatment with vardenafil was well tolerated, and headaches, flushing, nasal congestion, and dyspepsia were the most frequently observed adverse events.. Vardenafil was effective and well tolerated in men with moderate to severe erectile dysfunction. Treatment with vardenafil was associated with a significantly higher IIEF erectile function domain score and completion of successful intercourse rate compared with baseline.

Topics: Adult; Aged; Australia; Coitus; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; New Zealand; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Quality of Life; Severity of Illness Index; Sexual Behavior; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

We conducted a prospective, randomized, open-label, fixed-dose preference study, with a crossover design, using sildenafil, vardenafil, and tadalafil.. To assess patient preference for sildenafil (100 mg), vardenafil (20 mg), and tadalafil (20 mg) for the treatment of erectile dysfunction. Secondary objectives included finding out whether patients would follow treatment with a second or third option, in the event that the preferred drug was not available, and to assess side effects.. Patient preference for any treatment, and evaluation of the elements that patients would assess when choosing one of these drugs.. Sildenafil (100 mg), vardenafil (20 mg), and tadalafil (20 mg) were taken at least six times over a period of 45-60 days with a washout period of 7 days. A total of 132 patients were enrolled to achieve a valid sample of 90 cases (15 per randomized group, total of six groups). Enrolled patients had mild to moderate erectile function.. The International Index of Erectile Function (IIEF) score improved from baseline and was statistically significant in all cases (P < 0.0001). When we compared the IIEF scores, we found a statistically significant difference between tadalafil and vardenafil (P = 0.0002) favoring the former; similar results were obtained with the Erectile Dysfunction Inventory for Treatment Satisfaction (EDITS) Questionnaire (P = 0.000075). We also found a significant difference (P = 0.012) between tadalafil and sildenafil, again in favor of the former. In assessing drug preference, 25 patients (27.77%) chose sildenafil, 18 (20%) vardenafil, and 47 (52.22%) tadalafil. A total of 94% of patients would be willing to take another drug if the preferred choice was not available. All drugs were well tolerated.. Although this is a preference study based on subjective elements, statistically significant differences comparing the IIEF score and the EDITS Questionnaire lead us to believe that beyond patients' subjective preference per se, said preference is probably also based on a genuinely superior response to one drug over another.

Topics: Aged; Carbolines; Coitus; Cross-Over Studies; Dose-Response Relationship, Drug; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Purines; Quality of Life; Severity of Illness Index; Sexual Behavior; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Vardenafil is a highly selective phosphodiesterase type-5 inhibitor for the treatment of erectile dysfunction (ED). Efficacy of vardenafil has been demonstrated in various ED populations, but that in Japanese patients with spinal cord injury (SCI) has not been assessed.. This was an open-label, multicenter, flexible dose, 12-week study in patients with ED due to SCI. Following a 4-week observation period, patients received vardenafil 10 mg for 4 weeks, and based on efficacy, tolerability and patient preference, doses for the remaining 8 weeks were decided by investigators. The primary efficacy parameter was erectile function domain score of the International Index of Erectile Function.. Ten patients took 10 mg all through the study, while 22 patients took 20 mg after completing 4 weeks' treatment with 10 mg. The erectile function domain score increased from 12.2 at baseline to 25.0 at Last Observation Carried Forward (LOCF) in the former group and from 10.3 to 22.5 in the latter group, respectively. Importantly, there was a 5.0 point increase in erectile function domain score after up-titration in the latter group. Drug-related adverse events were observed in 22% of patients including hot flushes (9%) and headache (6%), but these were transient and mild in intensity. Serious adverse events and adverse events leading to discontinuation of the study drug were not reported.. Vardenafil 10 and 20 mg was well tolerated and improved erectile function in patients with SCI. Of interest, erectile function was further improved by 20 mg in patients who were not sufficiently treated with 10 mg.

Topics: Adult; Dose-Response Relationship, Drug; Drug Administration Schedule; Erectile Dysfunction; Headache; Hot Flashes; Humans; Imidazoles; Japan; Male; Middle Aged; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Spinal Cord Injuries; Sulfones; Time Factors; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) is a common condition with diverse sequelae affecting men and their women partners.. The FINDER study aimed to evaluate the efficacy and tolerability of the phosphodiesterase type-5 (PDE5) inhibitor, vardenafil, in a broad population of PDE5-naïve men with ED of different etiologies and severity and included their partners' assessments of treatment with vardenafil.. Men with ED (N = 260) were randomized to receive either vardenafil or placebo in a multicenter, flexible-dose study.. Primary efficacy variables were patients' responses to the Global Assessment Question (GAQ), and Sexual Encounter Profile questions 2 and 3 (SEP2 and SEP3).. Compared with placebo, vardenafil significantly improved rates of successful "Yes" responses to SEP3 ("Did your erection last long enough for you to have successful intercourse?") (49% placebo vs. 78% vardenafil at last period carried forward [LPCF]; P < 0.0001), SEP2 ("Were you able to insert your penis into your partner's vagina?") (65% placebo vs. 85% vardenafil at LPCF; P < 0.0001), and GAQ (36% placebo vs. 83% vardenafil at last observation carried forward; P < 0.0001). In addition, patients' and their partners' Treatment Satisfaction Scale (TSS) scores were statistically significantly improved across each of the TSS domains (satisfaction with orgasm, ease with erection, confidence, pleasure, erectile function satisfaction, and satisfaction with medication) in the vardenafil group compared with the placebo group.. Vardenafil improved sexual function to the extent that both patients and their partners expressed a considerable and agreed level of satisfaction with treatment.

Topics: Adult; Double-Blind Method; Erectile Dysfunction; Female; Humans; Imidazoles; Male; Middle Aged; Personal Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Quality of Life; Research Design; Sexual Partners; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Data from head-to-head clinical trials of phosphodiesterase type 5 (PDE5) inhibitors are scarce, making it difficult for clinicians to differentiate among these agents to select the most appropriate treatment for their patients with erectile dysfunction (ED).. This randomized, double-blind, crossover head-to-head clinical trial compared patient preference, efficacy, and safety of vardenafil and sildenafil in men with ED and diabetes, hypertension, and/or hyperlipidemia.. Prospective analysis was performed on two studies in which 1,057 men were randomized to vardenafil 20 mg (N = 530) or sildenafil 100 mg (2 x 50 mg encapsulated tablets) (N = 527) for 4 weeks. Following a 1-week washout, patients switched treatment for 4 weeks.. Patients were asked about overall preference: "Overall, which medication do you prefer?", plus 11 other preference questions relating to their ED treatment. Efficacy assessments after each treatment period included the erectile function (EF) domain score of the International Index of Erectile Function (IIEF); Sexual Encounter Profile (SEP) diary questions SEP2 and SEP3; Global Assessment Question (GAQ); and Treatment Satisfaction Scale (TSS). Data regarding adverse events were collected throughout the study.. A total of 931 men (mean age 57.9 years) were included in the intent-to-treat (ITT) population. Non-inferiority of vardenafil over sildenafil was achieved for overall preference (vardenafil 38.9%; sildenafil 34.5%; and no preference 26.6%). Additionally, the change from baseline in the EF domain score of the IIEF achieved nominal significance for vardenafil over sildenafil (10.00 vs. 9.40; P = 0.0052). Patients also had a higher percentage of positive responses for vardenafil for SEP2, SEP3, GAQ, and 12 of 19 questions on the TSS. Both drugs were well tolerated.. This randomized, double-blind, head-to-head trial in ED patients with cardiovascular risk factors demonstrated noninferiority of vardenafil for overall preference. Vardenafil achieved nominal statistical superiority over sildenafil for several frequently used efficacy measures. Both drugs were well tolerated.

Topics: Adult; Aged; Cardiovascular Diseases; Cross-Over Studies; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Purines; Severity of Illness Index; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Nerve sparing radical retropubic prostatectomy (NS-RRP) results in erectile dysfunction in a significant number of patients. Vardenafil, a potent and selective phosphodiesterase type 5 inhibitor, is generally safe. It improves International Index of Erectile Function erectile function domain scores, and penetration and erection maintenance success rates in patients who have undergone NS-RRP. We report additional parameters important to patient perceptions regarding erection quality and satisfaction with sexual experience following NS-RRP.. A total of 440 men at 58 centers throughout the United States and Canada participated in this randomized, placebo controlled, double-blind trial with 3 phases, namely baseline (4-week untreated period), treatment (12 weeks) and followup (7 days). Participants received placebo (145), 10 mg vardenafil (146) or 20 mg vardenafil (149) at home on demand but no more than once per calendar day. Efficacy and satisfaction with erection quality and sexual experience were determined during the trial.. The 10 and 20 mg vardenafil doses were significantly superior to placebo for the International Index of Erectile Function domains for intercourse satisfaction, orgasmic function and overall satisfaction with sexual experience (vs placebo p <0.0009). Significant improvement in the satisfaction rate with erection hardness were demonstrated for each vardenafil dose compared with placebo (p <0.0001). Vardenafil was generally well tolerated. Common adverse events were headache, vasodilatation and rhinitis.. In this difficult to treat population of men with erectile dysfunction subsequent to NS-RRP on demand treatment with vardenafil during a 3-month period significantly improved key aspects of the sexual experience important to patient quality of life.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Cyclic Nucleotide Phosphodiesterases, Type 5; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Follow-Up Studies; Humans; Imidazoles; Male; Middle Aged; Orgasm; Patient Satisfaction; Penile Erection; Penis; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Postoperative Complications; Prostatectomy; Quality of Life; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To assess success rates in ability to penetrate (Sexual Encounter Profile question 2 [SEP2]) and maintain erections to completion of intercourse (SEP3) from time of dosing to start of sexual activity in a retrospective analysis of two pivotal trials.. In two randomized, double-blind studies, men with ED for > 6 months received vardenafil 5 mg, 10 mg, or 20 mg or placebo for 12-26 weeks. Patients were instructed to start sexual activity 1 hour after dosing. In this retrospective pooled analysis, patient diary questions through week 12 were analyzed, providing attempt data was recorded 0-12 hours post-dose. Mean per-patient SEP2 and SEP3 success rates (intent-to-treat population) were calculated by time between dosing and start of sexual activity, from 0-12 hours through week 12. Least-square means and nominal p-values for differences versus placebo were derived by analysis of covariance with terms for baseline, study and treatment.. Most attempts at sexual intercourse occurred 30-90 minutes after dosing: 88%-93% of attempts occurred within 120 minutes. SEP2 success rates in patients choosing to attempt sexual activity in each interval from < or = 15 minutes through the 4-8-hour interval were higher with vardenafil compared with placebo, while SEP3 success rates were greater with vardenafil for patients choosing to initiate sexual activity from < or = 15 min through the 8-12-hour interval. The most commonly reported treatment-emergent adverse events in patients receiving vardenafil included headache (11%-22%), flushing (6%-13%), rhinitis (5%-13%), and dyspepsia (2%-7%).. In this retrospective analysis of two pivotal trials, vardenafil improved success rates compared with placebo in ED patients who attempted intercourse from as early as 15 minutes or less and through 4-8 hours after dosing in ability to penetrate (SEP2) and from as early as 15 minutes or less and through 8-12 hours after dosing in maintenance of erection (SEP3).

Topics: Coitus; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Headache; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Placebos; Retrospective Studies; Sulfones; Triazines; Vardenafil Dihydrochloride

To evaluate the reliability, efficacy, and safety of vardenafil, 10 mg, for patients with erectile dysfunction.. Vardenafil-naive patients completed a 4-week treatment-free run-in phase and a 1-week single-dose vardenafil (10 mg) open-label challenge phase. Responders to vardenafil in the challenge phase were randomized to 12 weeks of double-blind, fixed-dose treatment with vardenafil at 10 mg or placebo. Diary responses to Sexual Encounter Profile (SEP) questions about erections and attempts at sexual activity were collected after 4, 8, and 12 weeks of randomized treatment. Adverse events were monitored throughout the study.. During the open-label challenge phase, the proportions of patients with a first-time success for penetration (SEP2) and maintenance of erection (SEP3) were 87% and 74%, respectively. Of 600 patients challenged with a single dose of vardenafil at 10 mg, 260 were randomized to vardenafil and 263 to placebo. During the double-blind phase, the reliability of penetration and maintenance rates for patients successful during the challenge phase were significantly greater with vardenafil compared with placebo (83.4% vs 55.8% [SEP2] and 76.6% vs 42.1% [SEP3], respectively). At week 12, patients in the vardenafil group had a consistently higher least squares mean (SE) on the erectile function domain score of the International Index of Erectile Function than patients in the placebo group (23.5 [0.4] vs 15.8 [0.4], respectively [last observation carried forward]) and a greater proportion of positive responses to the Global Assessment Question (80.8% vs 32.3%, respectively [last observation carried forward]) at each assessment (Pc.001). Vardenafil was generally well tolerated; most adverse events were mild to moderate, with headache and flushing reported most frequently.. During this 12-week study, vardenafil produced consistently higher reliability of penetration and maintenance of erection rates compared to placebo and was generally well tolerated in patients with erectile dysfunction.

Topics: Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Sulfones; Triazines; Vardenafil Dihydrochloride

There are limited data concerning the sexual function of women whose male partners receive pharmacological treatment for erectile dysfunction (ED).. One objective of this research was to prospectively compare the efficacy of vardenafil vs. placebo administered to men with ED in improving men's and women partners' sexual function and satisfaction. Another goal was to assess the relationship of erectile function changes in men with ED receiving treatment with sexual function changes in women partners not directly receiving treatment.. A randomized, double-blind, placebo-controlled, multi-institutional comparison of vardenafil vs. placebo was performed in 229 couples (treated man with ED>6 months and untreated woman partner). Co-primary outcomes for which this research was statistically powered were Sexual Encounter Profile (SEP3) (treated man with ED) and Sexual Life Quality Questionnaire (mSLQQ-QOL) (untreated woman partner).. Erectile function changes in men with ED receiving vardenafil vs. placebo were compared at last observation carried forward (LOCF) in SEP3, International Index of Erectile Function (IIEF-EF) and Erection Quality Scale (EQS). Sexual function at LOCF in women partners was determined by mSLQQ-QOL and Female Sexual Function Index (FSFI).. Compared with placebo at LOCF, vardenafil significantly increased least square (LS) mean scores in: (i) overall per-treated male SEP3 success rate, IIEF-EF, and EQS; and (ii) mSLQQ-QOL, total FSFI and sexual desire, subjective arousal, lubrication, orgasm and satisfaction FSFI domains in untreated women partners. Treatment-related improvement in erectile function as assessed by IIEF-EF and EQS was correlated reliably with improvement in women partners' FSFI total and individual domain scores.. Vardenafil is an effective ED treatment in men that also significantly improves sexual function/satisfaction in untreated women partners. Women partners' sexual function improvements relate significantly and consistently to treatment-related improvements in men's erectile function. ED management should emphasize both members of the couple.

Topics: Adult; Aged; Double-Blind Method; Erectile Dysfunction; Female; Humans; Imidazoles; Male; Middle Aged; Personal Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Sexual Partners; Sexuality; Sulfones; Surveys and Questionnaires; Triazines; Vardenafil Dihydrochloride

To evaluate the efficacy, safety, and tolerability of a flexible-dose regimen of vardenafil in a community-based population of men with erectile dysfunction (ED).. This was a 12-week, open-label, flexible-dose, multicenter study of unselected men with ED of diverse origins and severity. Unlike previous studies, prostatectomy-induced ED and previous unresponsiveness to sildenafil were not exclusion criteria. After 4 weeks of treatment with 10 mg of vardenafil, the dose could be continued or titrated to 5 mg or 20 mg, depending on efficacy and tolerability. After 8 weeks, another dose change was possible. Efficacy was assessed with International Index of Erectile Function erectile function (IIEF-EF) domain scores, diary questions of the Sexual Encounter Profile (SEP), and a global assessment question (GAQ) about erection improvement during the previous 4 weeks.. Safety was evaluated in 497 patients, and 480 were suitable for intention-to-treat analysis. After 12 weeks of treatment, the mean per patient rate of successful intercourse, defined by an affirmative response to SEP questions 1-3, was 72%, and was related to age and ED duration. The overall success rate increased from 66% at week 4 to 77% at week 12. The mean IIEF-EF domain score of the whole population increased from 17.2 (baseline) to 24.4 (endpoint). At week 12, the best scores were obtained by patients taking 5 mg and 10 mg. At week 12, GAQ scores showed improved erection in 97.4%, 94.8%, and 78.8% of patients in the 5 mg, 10 mg, and 20 mg group, respectively. Safety was excellent: no serious drug-related event was reported, and only 2.2% of patients discontinued treatment because of side-effects.. Vardenafil was effective and well tolerated in this community-based ED population that is truly representative of the general ED population. Dose titration meets the patient's needs and optimizes clinical outcome.

Topics: Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Residence Characteristics; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Vardenafil, a phosphodiesterase type 5 (PDE5) inhibitor, was evaluated in a prospective trial in the primary care setting involving hypertensive men with ED who were receiving at least one antihypertensive medication.. To investigate the safety and efficacy of flexible-dose vardenafil therapy compared with placebo in PDE5 inhibitor-naïve subjects with arterial hypertension and ED.. In this multicenter, randomized, double-blind, placebo-controlled study, 354 patients received placebo or vardenafil (5-20 mg) for 12 weeks. Primary efficacy measures were diary responses to the Sexual Encounter Profile (SEP) questions 2 (vaginal insertion) and 3 (maintenance of erection). Additional efficacy measures included positive responses to the Global Assessment Question (GAQ).. Compared with placebo, vardenafil significantly improved mean SEP2 and SEP3 success rates over the 12-week study period (intention-to-treat [ITT] and last observation carried forward [LOCF]) analysis). For LOCF, SEP2 and SEP3 were 83% for vardenafil vs. 58% for placebo and 67% for vardenafil vs. 35% for placebo, respectively (P<0.0001 vs. placebo). Improved erections (GAQ) were experienced by 80% of vardenafil-treated patients at study end, compared with 40% for placebo (P<0.0001, LOCF). The most commonly reported treatment-emerging adverse events were headache (3.1%) and flushing (1.6%), which were mild-to-moderate and transient in nature. Importantly, there were no significant changes in systolic and diastolic blood pressure or heart rate between the vardenafil and placebo groups. The average number of antihypertensives used per patient was 1.5 and 1.4 in the vardenafil and placebo groups, respectively. Both the incidence of adverse events and the ability to maintain an erection were unaffected by stratification into distinct subsets according to the class of antihypertensive medication being received.. Vardenafil significantly improves EF in hypertensive men treated with concomitant antihypertensive medication, is well tolerated, and does not significantly affect blood pressure.

Topics: Adult; Aged; Antihypertensive Agents; Double-Blind Method; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Risk Factors; Safety; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) has a dual negative impact on men and their female partners; both are likely to face a drop in sexual quality of life and challenges to their intimate relationship as couples' sexual activities are curtailed by the loss of erectile function.. The primary objective of this study was to compare the efficacy of vardenafil vs. placebo in terms of success of maintenance of erection in men with ED and improvement of their female partner's sexual quality of life.. This was a randomized, double-blind, multicenter, flexible-dose, parallel-group comparison of vardenafil vs. placebo for 12 weeks in men (> or =18 years) with ED of > or = 6 months duration, and their female partners.. Changes in patient's overall response rate to Sexual Encounter Profile question 3 (SEP3) "Did your erection last long enough for you to have sexual intercourse?" and female partner's response to the quality of life domain of the modified Sexual Life Quality Questionnaire (mSLQQ-QOL) at last observation carried forward (LOCF) were considered the primary efficacy measures. In addition, patient's response to SEP2 "Were you able to insert your penis into your partner's vagina?," the erectile function domain of the International Index of Erectile Function (IIEF-EF) and patient's mSLQQ-QOL score were also assessed.. Compared with placebo, vardenafil significantly improved overall least square (LS) mean per-patient SEP3 success rate (28% vs. 68%; P < 0.0001) and partner's LS mean (standard error [SE]) mSLQQ-QOL score at LOCF (32.14 [3.24] vs. 65.80 [3.10]; P < 0.0001). In addition, compared with placebo, vardenafil also improved overall LS mean per-patient SEP2 success rate (47% vs. 80%; P < 0.0001), LS mean (SE) IIEF-EF scores at LOCF (12.7 [0.8] vs. 22.8 [0.8]; P < 0.0001) and patient's LS mean (SE) mSLQQ-QOL (28.37 [3.46] vs. 63.85 [3.28]; P < 0.0001) at LOCF.. Vardenafil improved erectile function in men with ED and improved the sexual quality of life of the couple.

Topics: Double-Blind Method; Erectile Dysfunction; Female; Humans; Imidazoles; Male; Middle Aged; Personal Satisfaction; Piperazines; Quality of Life; Sexual Behavior; Sexual Partners; Sulfones; Surveys and Questionnaires; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Vardenafil is a potent and selective phosphodiesterase 5 (PDE5) inhibitor developed for the treatment of erectile dysfunction (ED). Fixed-dose and flexible-dose studies have previously established the efficacy and tolerability of vardenafil.. To assess, besides the usual measures of efficacy, the quality of erection, satisfaction with the sexual experience, symptoms of depression, and overall confidence.. This 12-week double-blind, placebo-controlled flexible-dose study assessed patients from the general ED population. Patients underwent a 4-week treatment-free period before randomization to vardenafil or matching placebo. Initial dosage was vardenafil 10 mg for 4 weeks. At 4 weeks, patients could switch to 5 or 20 mg (or corresponding placebo), or remain on 10 mg for an additional 4 weeks; dose switching was also optional for the last 4 weeks. This paper describes per-patient success in satisfaction with hardness of erection, satisfaction with overall sexual experience, effect on overall self-confidence, and an assessment of symptoms of depression using the Center for Epidemiologic Studies Depression Scale.. Mean per-patient satisfaction rates with erection hardness increased after vardenafil treatment to 43%, 59%, and 63% at weeks 4, 8, and 12, respectively, compared to placebo with 10%, 21%, and 23% (all P < 0.005 vs. placebo). Vardenafil also improved mean per-patient overall satisfaction 50-65% over the 4-12 week study period compared with 17-28% for placebo (P < 0.005). Symptoms of depression were statistically significantly reduced compared to placebo (P = 0.02); the effect was observed particularly in patients who were depressed at baseline (P = 0.01). Significantly more patients in the vardenafil treatment group reported improved self-confidence than those who received placebo (P < 0.005).. A flexible-dose regimen of vardenafil improved satisfaction rates, symptoms of depression, and self-confidence, providing patients with an effective ED therapy that contributes to overall improvements in sexual function and confidence.

Topics: Analysis of Variance; Depression; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Logistic Models; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Self Concept; Sulfones; Triazines; Vardenafil Dihydrochloride

In the multicenter STEADY-(safety, tolerability, efficacy and impact on quality of life of vardenafil 10 mg in patients with erectile dysfunction)-study, 996 patients with erectile dysfunction were treated with vardenafil for a period of 12 weeks. The results within a time window of up to 6 hours post-administration and beyond (up to 12 hours) were evaluated. The effectiveness of vardenafil was analysed on the basis of the parameters Sexual Encounter Profile (SEP) 2 (vaginal penetration) and SEP3 (erection maintenance) as also the "erectile function score" and overall satisfaction.. On the occasion of the first follow-up 4 weeks after the administration of vardenafil there was an appreciable improvement in all four parameters. Very high success rates were observed not only during the primarily investigated time window of 6 hours, but also beyond this (up to 12 hours). Satisfaction with sexual intercourse (SI) increased from 24.6% prior to treatment to 87.6% at the end of the 12-week treatment period.. Under doctor's office conditions vardenafil was reliable and highly effective, already at the 10 mg dose, when the patients utilized its effect within a time window ranging from < 0.5 to 12 hours (tablet ingestion to SI). In addition, vardenafil was very well tolerated. Patient satisfaction with the treatment was reportedly very high.

Topics: Adolescent; Adult; Aged; Coitus; Drug Administration Schedule; Erectile Dysfunction; Follow-Up Studies; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Time Factors; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

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.. 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.. 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.. In this flexible dose study, vardenafil was well-tolerated, and produced clinically relevant improvements in erectile function in men with ED.

Topics: Erectile Dysfunction; Europe; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Sulfones; Surveys and Questionnaires; Triazines; Vardenafil Dihydrochloride

This randomised, double-blind study assessed the long-term efficacy and tolerability of vardenafil 10 and 20 mg in men with erectile dysfunction (ED). A total of 566 men who completed an initial 12-month treatment period entered a 12-month extension. In these men, both doses of vardenafil produced improvement in scores for the 'erectile function' Domain of the International Index of Erectile Function, evident from week 4 and maintained through 2 years. Sexual Encounter Profile diary responses indicated that following treatment, penetration was achieved on 92-94% of attempts and erections that lasted long enough for successful intercourse were achieved on 87-89% of attempts. In response to the General Assessment Question, 90-92% of patients reported improved erections with vardenafil. Most treatment-emergent events were mild and transient with no cardiovascular safety concerns. These results support the long-term efficacy, reliability and tolerability of vardenafil 10 and 20 mg in men with ED.

Topics: Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To determine the efficacy and tolerability of flexible dosing with vardenafil in a broad population of men with erectile dysfunction (ED).. 10-week, open-label, flexible-dose study starting with vardenafil 10 mg, titrating to 5 mg or 20 mg at weeks 2 and 6 based on efficacy and tolerability, set in 78 community practice centers in Germany and France. Participants comprised 398 men aged > or =18 years with ED. Main outcome measures were self-reported improvement in erections according to a Global Assessment Question (GAQ), diary questions from the Sexual Encounter Profile (SEP2 and SEP3), and the erectile function domain score from the International Index of Erectile Function (IIEF) questionnaire.. In a last observation carried forward (LOCF) analysis, a total of 92% (336/366) of men with ED reported an improvement of erections according to the GAQ. Per-patient success rates for penetration (SEP2) and maintenance (SEP3) of erection for intercourse were 89% (348/390) and 78% (303/390), respectively. Mean erectile function domain scores increased from 13.9 at baseline to 25.9 at LOCF. Vardenafil was generally well tolerated; headache (6%, 25/398) and flushing (6%, 24/398) were the most frequent adverse events.. In this community practice setting, vardenafil was shown to be a highly effective and generally well-tolerated treatment for men with ED when dosing was titrated by the physician to individual patient requirements.

Topics: Adult; Aged; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

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.. 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).. 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.. 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.

Topics: Adult; Aged; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Japan; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Sulfones; Triazines; Vardenafil Dihydrochloride

Vardenafil is an oral, potent, highly selective phosphodiesterase 5 (PDE5) inhibitor. It improves erectile function significantly regardless of the etiology and severity of erectile dysfunction (ED) or the age of the patients. Its onset time leading to successful intercourse is as short as 10 minutes after administered orally, and in most patients it works persistently. Adverse reactions are generally transient and mild to moderate in nature. So vardenafil is both effective and safe for men with ED.

Topics: Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) usually exists in combination with depression in men. The comorbidity of the two diseases may bring more troubles to patients, so it is important to find an effective treatment. Recently, DRIVER (Depression Related Improvement with Vardenafil for Erectile Response) trials showed that, phosphodiesterase 5 (PDE 5) inhibitor vardenafil could improve not only erectile function but also depressive symptoms and quality of life in men with ED and depression. Vardenafil was generally safe and well tolerated.

Topics: Adult; Aged; Aged, 80 and over; Depressive Disorder; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Quality of Life; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To evaluate the efficacy of vardenafil in patients previously unresponsive to sildenafil.. A multicentre, double-blind, 12-week, flexible-dose, placebo-controlled trial was conducted, involving 463 men aged > or = 18 years with moderate-to-severe erectile dysfunction (ED) and who were unresponsive to sildenafil (by history). After a 4-week treatment-free run-in, patients received placebo or vardenafil 10 mg with the option to maintain current dose or to titrate by one dose level (5, 10 or 20 mg) based on efficacy and tolerability at 4 and 8 weeks. Outcome measures were the erectile function (EF) domain score of the International Index of Erectile Function, two Sexual Encounter Profile diary questions (vaginal penetration and maintenance of erection until successful completion of intercourse), and the Global Assessment Question (GAQ).. There was significantly better EF with vardenafil than with placebo throughout the study. The least-square mean EF domain scores increased from 9.3 at baseline to 17.6 at the 'last' observation carried forward (LOCF) analysis with vardenafil (P < 0.001). Overall least-square mean per-patient success rates more than doubled for penetration (30.3% to 62.3%) and quadrupled for successful intercourse (10.5% to 46.1%) with vardenafil. Improved erections (positive response to the GAQ) were reported by 61.8% of patients receiving vardenafil and 14.7% of those receiving placebo at LOCF (P < 0.001). Normal EF (domain score > or = 26) was achieved by 30% of patients receiving vardenafil and 6% receiving placebo at LOCF (P < 0.001). Adverse events were infrequent and representative of the phosphodiesterase-5 inhibitor profile.. Vardenafil is an effective and generally safe treatment for ED, even in men unresponsive to sildenafil (by history).

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

To evaluate the efficacy and safety of vardenafil on men with erectile dysfunction (ED) of various etiologies.. A total of 88 men with mild to severe erectile dysfunction were enrolled in the randomized, double-blind, placebo-controlled, fixed-dose trial of 12 weeks of treatment with either placebo or 5, 10 and 20 mg of vardenafil.. This study indicated that vardenafil dosages of 5, 10 and 20 mg were significantly superior to placebo for the treatment of ED, on the basis of the primary study endpoints of the EF domain score of the IIEF, diary-recorded success rates for penetration and maintenance of erection during the intercourse and the GAQ. Vardenafil was well tolerated. The incidence of adverse events was higher for vardenafil than for placebo.. Oral vardenafil therapy has a high efficacy and a low incidence of adverse events for ED patients with mixed etiologies.

Topics: Administration, Oral; Adult; Aged; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

Vardenafil (Levitra) is a potent and selective phosphodiesterase 5 (PDE5) inhibitor used in the management of erectile dysfunction (ED). This retrospective subgroup analysis assessed the effectiveness of vardenafil treatment in men with ED of different baseline severity and disease classification.. Data from two pivotal, randomized, double-blind, placebo-controlled clinical trials enrolling men from the general ED population who received placebo or vardenafil 5 mg, 10 mg, or 20 mg during a 12-week treatment period were retrospectively analysed, stratifying by psychogenic, organic, and mixed ED disease classification as determined by the investigator. Efficacy endpoints included the International Index of Erectile Function (IIEF)-Erectile Function (EF) domain score, per-patient diary response rates to questions on penile insertion [Sexual Encounter Profile (SEP-2)] and maintenance of erection (SEP-3) and rates of positive response to the Global Assessment Question (GAQ).. Data from 1,385 men who received at least one dose of study medication and had pre- and post-baseline measures of efficacy available (intent-to-treat population) are presented. At baseline 37-41% of patients had severe ED, 30-34% moderate, 22% mild-to-moderate and 6-8% mild ED. At baseline, 46-51% of patients were considered to have an organic cause for ED, 13-16% psychogenic ED, and 36-38% mixed classification of ED. For all classifications and for mild-to-moderate to severe ED, men treated with 10 or 20 mg of vardenafil showed statistically and clinically significant improvements (P < 0.001) in IIEF-EF scores, diary response rates to the SEP-2 and SEP-3 questions, and GAQ as compared with those given placebo. The greatest improvements relative to placebo were noted in patients with more severe ED. The most common treatment-emergent adverse events were headache, flushing, rhinitis, dyspepsia, and were dose-related, mostly mild to moderate in intensity and consistent with the class.. Vardenafil improves EF in men with ED irrespective of investigator-determined classification and baseline ED severity.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Cyclic Nucleotide Phosphodiesterases, Type 5; Double-Blind Method; Drug Administration Schedule; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Penile Erection; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Retrospective Studies; Severity of Illness Index; Sulfones; Triazines; Vardenafil Dihydrochloride

Vardenafil, a potent and selective oral PDE5 inhibitor, is efficacious and generally well-tolerated in men with erectile dysfunction (ED). Of considerable interest to patients and physicians is an understanding of the time required after dosing to attain penile erection sufficient for successful sexual intercourse.. To determine the earliest time to onset of action of vardenafil 10 and 20 mg leading to successful intercourse compared to placebo in men with ED.. A prospective, randomized, double-blind, parallel-group, at-home study of 732 men with ED (mean age 55.5 years) was conducted at 64 sites in North America and Europe. Following a 4-week run-in period, patients were randomized to either vardenafil 10 (N = 237) or 20 mg (N = 248) or placebo (N = 247) to be taken on demand over 4 weeks. Using a stopwatch, patients recorded the elapsed time from dosing to attainment of an erection perceived to be adequate for penetration that led to intercourse completion. Earliest time of onset was defined as the fastest time among the first four doses for each patient. Time points from 25 to 5 minutes were tested for significance (alpha = 0.025) using a backward stepping procedure.. Mean baseline erectile function domain score (13.4) indicated moderate ED. Within 25 minutes after dosing, 50%/53% of men on vardenafil 10/20 mg had at least one erection in the first four doses perceived to be sufficient for penetration with subsequent intercourse completion compared to 26% on placebo (P < 0.0001). A statistically superior response to vardenafil vs. placebo was observed in these responders at all times >or= 10 and >or= 11 minutes (P < 0.025) in the 10 and 20 mg groups, respectively. In a retrospective analysis using time intervals of

Topics: Adult; Coitus; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Flushing; Headache; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Placebos; Prospective Studies; Sexual Behavior; Sulfones; Time Factors; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

The North American Pivotal Trial was designed to investigate the efficacy and safety of vardenafil in males with erectile dysfunction (ED).. In this randomized, double-blind, placebo-controlled, multicenter, fixed-dose, parallel group, 6-month study, vardenafil at three doses (5 mg, 10 mg, and 20 mg) was compared to placebo with the primary efficacy variables being the International Index of Erectile Function (IIEF) Erectile Function (EF) domain score and per patient diary response success rates for penetration and maintenance of erection through completion of intercourse. Additional efficacy variables included IIEF domain scores measuring intercourse satisfaction, orgasmic function, sexual desire, and overall satisfaction. Diary entries for overall per patient satisfaction rates for hardness and sexual experience were also measured. Improvements in quality of sexual life were assessed using the Fugl-Meyer quality of life (QoL) questionnaire.. Compared to placebo, patients taking 10 mg and 20 mg doses of vardenafil showed statistically significantly greater improvement in IIEF domain scores measuring intercourse satisfaction (10.3 and 10.3 vs. 7.7), orgasmic function (7.1 and 6.9 vs. 5.3), overall satisfaction. (7.1 and 7.1 vs. 5.2) for vardenafil 10 mg and 20 mg vs. placebo, respectively, at last observation carried forward (LOCF). Vardenafil 5 mg was statistically significantly better than placebo for the secondary IIEF domain variables of intercourse satisfaction (8.9 vs. 7.7) and overall satisfaction (6.3 vs. 5.2) for vardenafil vs. placebo, respectively, at LOCF. Per patient satisfaction rates for the secondary diary variables measuring erection hardness (38%, 52%, 58% and 18%) and overall satisfaction (45%, 58%, 62% and 23%) were dose dependent and statistically significantly superior for vardenafil at 5 mg, 10 mg and 20 mg compared with placebo, respectively. Patients' answers to the Fugl-Meyer QoL questionnaire assessing improvement in sexual life also indicated statistically significant superiority for all doses of vardenafil vs. placebo treatment. The most frequent adverse events (AE) in the 5 mg, 10 mg, and 20 mg of vardenafil and placebo groups, respectively, were: headache (10%, 22%, 21% and 4%), flushing (5%, 10%, 13% and 0%), dyspepsia (1%, 4%, 6% and < 1%), and rhinitis (9%, 14%, 17% and 5%). Most AEs were mild or moderate in severity and transient in nature.. Vardenafil was superior to placebo for IIEF domain scores, per patient success rates for diary questions, and assessment of quality of sexual life, in a broad range of patients with ED irrespective of etiology or severity. Vardenafil was generally well tolerated, with most AEs being mild or moderate in severity and transient in nature.

Topics: Adult; Canada; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Flushing; Headache; Humans; Imidazoles; Male; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Placebos; Quality of Life; Sexual Behavior; Sulfones; Surveys and Questionnaires; Time Factors; Treatment Outcome; Triazines; United States; Vardenafil Dihydrochloride

This study evaluated the efficacy and safety of vardenafil treatment for erectile dysfunction (ED) in men with diabetes.. In this prospective multicenter double-blind placebo-controlled fixed-dose parallel-group phase III trial, 452 patients with diabetes (type 1 or type 2) and ED were randomized to take 10 or 20 mg vardenafil or placebo as needed for 12 weeks. Efficacy responses were assessed by International Index of Erectile Function domain scores, rates of vaginal penetration and successful intercourse, and a global assessment question (GAQ) about erection improvement during the previous 4 weeks.. After 12 weeks of treatment, a dose-dependent (P = 0.02) improvement in erections was noted for the GAQ, with 57 and 72% of men taking 10 mg or 20 mg vardenafil, respectively, reporting improved erections, in contrast to 13% after taking placebo (P < 0.0001). For the erectile function domain, dose-dependent (P = 0.03) final scores for the 10- and 20-mg dose were 17.1 and 19.0 compared with 12.6 for placebo (P < 0.0001). Both vardenafil doses significantly enhanced the rates of successful penetration (P < 0.0001) and successful intercourse (P < 0.0001) compared with placebo. Vardenafil treatment was effective in increasing intercourse success rates at all levels of baseline ED severity, at each level of plasma HbA(1c), and for type 1 and 2 diabetes. Treatment-emergent adverse events were primarily mild to moderate headache (

Topics: Administration, Oral; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

The effects of food on the pharmacokinetics of vardenafil were examined in 25 healthy adult males. Single-dose vardenafil 20 mg was administered in a randomized four-way crossover design after an overnight fast (at 8 a.m.), after consumption of a high-fat breakfast (at 8 a.m.), on an empty stomach (at 6 p.m.), and after a typical moderate-fat evening meal (at 6 p.m.). Serial blood samples were analyzed for vardenafil and metabolite (M1) levels. When administered after an overnight fast and after a high-fat breakfast, vardenafil geometric mean Cmax was 17.14 and 14.0 micrograms/L, respectively, and AUC was 66.78 and 67.09 micrograms./h/L, respectively; the median tmax was 1 hour under fasting conditions and 2 hours with consumption of high-fat breakfast. When administered in the evening on an empty stomach and after a moderate-fat meal, vardenafil geometric mean Cmax was 14.22 and 13.04 micrograms/L, respectively, and AUC was 51.97 and 59.12 micrograms.h/L, respectively. The median tmax was 1 hour after fasting or a moderate-fat meal in the evening. All treatments were well tolerated. Thus, while a high-fat meal may alter Cmax slightly and delay the absorption up to 1 hour, a moderate-fat meal has no clinically relevant effect on vardenafil pharmacokinetics. Dosage changes are not warranted based on the wide therapeutic index and the efficacy observed with vardenafil in Phase III studies that were not restricted with respect to food.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Administration, Oral; Adult; Area Under Curve; Biological Availability; Cross-Over Studies; Cyclic Nucleotide Phosphodiesterases, Type 5; Dietary Fats; Drug Administration Schedule; Erectile Dysfunction; Food-Drug Interactions; Half-Life; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Postprandial Period; Sulfones; Time Factors; Triazines; Vardenafil Dihydrochloride

The durability of key efficacy response parameters and safety of vardenafil was evaluated in a pivotal trial conducted in a broad population of men with erectile dysfunction (ED) in North America. In this randomized, double-blind, placebo-controlled, multicenter, fixed-dose, parallel-group, 6-month comparison study, men >18 years of age with ED for >6 months received 5-mg, 10-mg, and 20-mg doses of vardenafil as needed for up to 26 weeks. The primary efficacy variables were the International Index of Erectile Function (IIEF)-Erectile Function (EF) domain scores, and the Sexual Encounter Profile (SEP) mean per-patient success rates for penetration (SEP question 2) and maintenance of erections (SEP question 3). Safety data were also collected over time. Improvement in all primary efficacy variables was observed in all vardenafil groups versus placebo. These improvements occurred early and were either sustained or increased through week 26. Vardenafil in 10-mg and 20-mg doses was significantly superior to placebo at all time points for all efficacy variables (P <0.01), and all doses were superior to placebo at endpoint (P <0.001). Most treatment-emergent adverse events (headache, flushing, dyspepsia, and rhinitis) were mild or moderate in intensity, and incidence generally decreased over time. All 3 doses of vardenafil were superior to placebo across all primary efficacy variables and all study time points in a broad range of patients with ED, regardless of etiology or severity. Vardenafil was well tolerated. These results demonstrate that vardenafil provides sustained efficacy with reduced incidence of nuisance side effects over time. High resolution video, medium resolution video, low resolution video.

Topics: Aged; Aged, 80 and over; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Placebos; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To assess whether vardenafil would improve erectile function irrespective of etiology, baseline severity, or patient age. The consistency of the response over time was also evaluated.. A multicenter, randomized, double-blind, placebo-controlled at-home study of vardenafil treatment (5, 10, and 20 mg) was performed. This secondary analysis compared the mean International Index of Erectile Function (IIEF) erectile function domain scores of various subgroups at 12 weeks of treatment. These populations included organic, psychogenic, or mixed etiologies; mild, moderate, or severe baseline severity; and four age groups (younger than 45, 45 to 55, 56 to 65, and older than 65 years). In addition, all IIEF domains were compared at sequential 4-week periods, before and during treatment.. In the 580 men of the intent-to-treat population, the mean erectile function domain scores were statistically greater than placebo, irrespective of etiology, baseline severity, or age. This was seen at all dosages. Compared with placebo, vardenafil statistically improved the IIEF domain scores of erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction after 4 weeks of treatment, and these improvements were maintained for 12 weeks. The rates of the most common adverse events (headache, flushing, and dyspepsia) were either constant or declined over time; they were generally mild to moderate and transient in nature.. Vardenafil improved erectile function regardless of the general etiology, baseline severity of erectile dysfunction, or patient age. Improvements in erectile function and other key IIEF domains were consistently seen throughout the study.

Topics: Aged; Aged, 80 and over; Coitus; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Headache; Humans; Imidazoles; Libido; Male; Middle Aged; Orgasm; Patient Satisfaction; Penile Erection; Piperazines; Sexual Behavior; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

More than one-third of men may experience erectile dysfunction (ED) after nerve sparing radical retropubic prostatectomy. The efficacy and safety of vardenafil, a potent, selective, phosphodiesterase 5 inhibitor, was assessed for the treatment of ED after radical prostatectomy.. In this double-blind study 440 men with ED after nerve sparing radical prostatectomy were randomized to take placebo, or 10 or 20 mg vardenafil. Efficacy was measured after 12 weeks using the erectile function domain of the International Index of Erectile Function, diary questions measuring vaginal penetration and intercourse success rates, and a global assessment question (GAQ) on erection.. Of the intent to treat population 70% had severe ED (erectile function less than 11) at baseline. After 12 weeks both vardenafil doses were significantly superior to placebo (p <0.0001) for all efficacy variables. Improved erections (based on GAQ) were reported by 65.2% and 59.4% of patients on 20 and 10 mg vardenafil, respectively, and by only 12.5% of patients on placebo (p <0.0001). Among men with bilateral neurovascular bundle sparing, positive GAQ responses were reported by 71.1% and 59.7% of patients on 20 and 10 mg vardenafil, respectively, versus 11.5% of those on placebo (p <0.0001). The average intercourse success rate per patient receiving 20 mg vardenafil was 74% in men with mild to moderate ED and 28% in men with severe ED, compared to 49% and 4% for placebo, respectively. Few adverse events were observed. They were generally mild to moderate headache, flushing and rhinitis.. In men with severe ED after nerve sparing radical retropubic prostatectomy, vardenafil significantly improved key indices of erectile function.

Topics: Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Piperazines; Prospective Studies; Prostatectomy; Sulfones; Triazines; Vardenafil Dihydrochloride

The effect of vardenafil, a potent and highly selective phosphodiesterase-5 (PDE5) inhibitor, on symptom-limited exercise time, time to first awareness of angina, and time to ischemic threshold (ST-segment depression > or =1 mm from baseline) during exercise tolerance testing (ETT) was examined in patients with stable coronary artery disease (CAD).. Erectile dysfunction (ED) is common among men with CAD. PDE5 inhibition is increasingly the preferred treatment option for ED. However, the effect of PDE5 inhibition on exercise-induced ischemia in CAD patients has received limited prospective evaluation.. In this double-blind, crossover, single-dose multicenter study, 41 men with reproducible stable exertional angina due to ischemic CAD received vardenafil 10 mg or placebo, followed by ETT (5 to 10 metabolic equivalents [METS], Bruce protocol) 1 h postdose. Sublingual nitrate use was prohibited for > or =24 h pre- and postexercise study days. End points included symptom-limited treadmill exercise time, time to first awareness of angina, time to ischemic threshold, and safety.. Relative to placebo, vardenafil 10 mg did not alter exercise treadmill time (427 +/- 105 s vs. 433 +/- 109 s, p = 0.39), or time to first awareness of angina (292 +/- 110 s vs. 291 +/- 123 s, p = 0.59), but significantly prolonged time to ischemic threshold (334 +/- 108 s vs. 381 +/- 108, p = 0.0004). At peak exercise, vardenafil 10 mg did not alter blood pressure, heart rate, or rate-pressure product relative to placebo. The most common adverse events (facial flushing and headache) were of mild or moderate intensity, and short-lived.. Vardenafil 10 mg did not impair the ability of patients with stable CAD to exercise at levels equivalent or greater than that attained during sexual intercourse (average of 2.5 to 3.3 METS).

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Aged; Aged, 80 and over; Blood Pressure; Cardiovascular System; Coronary Artery Disease; Cross-Over Studies; Cyclic Nucleotide Phosphodiesterases, Type 5; Diastole; Double-Blind Method; Electrocardiography; Erectile Dysfunction; Exercise; Exercise Test; Exercise Tolerance; Heart Rate; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Sulfones; Systole; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

The pharmacodynamic effect on penile rigidity and tumescence and the pharmacokinetic properties of single oral doses of 10 and 20 mg vardenafil, a new PDE5-inhibitor, were investigated in 21 erectile dysfunction patients. Patients were evaluated with RigiScan on three occasions in a randomized, placebo-controlled, double-blind crossover fashion, while receiving visual sexual stimulation. Relative to placebo, a single dose of 10 mg vardenafil led to a mean increase in the duration of >60% penile rigidity of 24.4 min (95% CI: 7.4 to 41.3) at the base and of 24.8 min (8.5 to 41.1) at the tip. For the 20-mg dose, the increase in duration of > 60% penile rigidity relative to placebo was 37.2 min (20.2 to 54.1) at the base and 28.7 min (12.7 to 44.7) at the tip. Single doses of 10 and 20 mg vardenafil led to a rapid rise in the plasma concentrations of vardenafil, with a median tmax of 0.9 h and 0.7 h and a geometric mean Cmax of 9.1 microg/l (geometric SD = 1.63) and 20.9 microg/l (geometric SD = 1.83), respectively. In the post-absorptive phase, the concentrations declined with an average terminal t 1/2 of 4.2 h (geometric SD = 1.27) and 3.9 h (geometric SD = 1.31). The systemic exposure of vardenafil expressed as AUC normalized for dose and body weight was dose-proportional (associated 90% CI: -4 to 30%) as well as Cmax (associated 90% CI: -12 to 33%). The treatments were well tolerated. There was a small, clinically irrelevant reduction in blood pressure with a small compensatory rise in heart rate. There were no electrocardiographic effects or relevant changes of the safety laboratory screens. The observed pro-erectile properties, pharmacokinetic characteristics and safety profile make vardenafil a suitable candidate for further evaluation in the treatment of erectile dysfunction.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adolescent; Adult; Cross-Over Studies; Cyclic Nucleotide Phosphodiesterases, Type 5; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Penile Erection; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

Vardenafil, a novel selective phosphodiesterase type 5 inhibitor, was evaluated in its first large-scale at-home trial. A total of 601 men with mild to severe erectile dysfunction (ED) were enrolled in this multi-centre, randomized, double-blind, placebo-controlled trial of 12 weeks of treatment with either placebo or 5, 10 and 20 mg of vardenafil. Primary endpoints were Q3 (vaginal penetration) and Q4 (maintenance of erection) of the International Index of Erectile Function (IIEF). In the intent-to-treat population (n=580), the changes from baseline for 5, 10 and 20 mg vardenafil (1.2, 1.3 and 1.5, respectively) were all improved (P<0.001) over placebo (0.2) for Q3 and were similarly improved for Q4 (1.4, 1.5 and 1.7) compared to placebo (0.5) (P<0.001). All vardenafil doses improved all IIEF domains compared to placebo (P<0.001). The percentage of successful intercourses was between 71 and 75% for the three vardenafil doses. For the 20 mg dose, 80% of the patients experienced improved erections (GAQ) compared to 30% for placebo. Most frequent treatment-emergent adverse events were headache (7-15%), flushing (10-11%) and up to 7% for dyspepsia or rhinitis. Vardenafil treatment resulted in a high efficacy and low adverse-event profile in a population with mixed ED etiologies.

Topics: Adult; Coitus; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Safety; Sulfones; Triazines; Vardenafil Dihydrochloride

To evaluate the effect of two doses of vardenafil hydrochloride on penile rigidity and tumescence while determining the pharmacokinetics.. Twenty-one patients with erectile dysfunction completed three oral single-dose regimens (placebo, 20 and 40 mg vardenafil) in a randomized, placebo-controlled, 3-way cross-over study. Penile rigidity and tumescence were measured at the base and tip with a Rigiscan for up to 2 h after dosing. The period included three 20-min repeated episodes of visual sexual stimulation. Blood samples were taken periodically up to 24 h after dosing.. After 20 and 40 mg vardenafil, the mean duration of >60% rigidity of the base of the penis was greater than after placebo by 42.9 min (95% Cl 29.3-56.4) and by 49.3 min (95% Cl 35.7-62.9), respectively (p<0.001), and greater than after placebo by 34.6 min (95% Cl 22.1-47.1) for both doses at the tip. Additionally, significantly greater rigidity activity units and tumescence activity units were found for both doses compared with placebo (p<0.001). The plasma concentrations of vardenafil increased rapidly, with a median t(max) of about 40 min and a mean t1/2 of 4.4-4.8 h. Relative bioavailability was slightly higher for the 40-mg dose than for the 20-mg dose. The treatments were well tolerated, although slightly more adverse events, primarily headache, flushing and nasal congestion, were seen with the 40-mg dose compared with placebo.. The findings confirm that vardenafil was able to generate stronger erections of longer duration than placebo under conditions of visual sexual stimulation in patients with erectile dysfunction. The pharmacokinetic, pharmacodynamic and tolerability profiles support vardenafil hydrochloride as a strong candidate for further testing as a treatment for erectile dysfunction.

Topics: Adolescent; Adult; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

Despite their efficacy and general safety, rare but devastating adverse drug reactions have been associated with phosphodiesterase type 5 inhibitors.. To determine the safety profile of oral phosphodiesterase type 5 inhibitors with a particular focus on priapism and malignant melanoma.. In this case-non-case study, we queried the individual case safety reports for phosphodiesterase type 5 inhibitors within the World Health Organization global database of individual case safety reports (VigiBase) between 1983 and 2021. We included all individual case safety reports for sildenafil, tadalafil, vardenafil, and avanafil in men. For comparison, we also extracted the safety data from the Food and Drug Administration trials for these drugs. We assessed the safety profile of phosphodiesterase type 5 inhibitors by disproportionality analysis by measuring reporting odds ratio for their most commonly reported adverse drug reactions, once for all phosphodiesterase type 5 inhibitor reports and once for reports of oral phosphodiesterase type 5 inhibitor use in adult men (≥18 years old) with sexual dysfunction.. A total of 94,713 individual case safety reports for phosphodiesterase type 5 inhibitors were extracted. A total of 31,827 individual case safety reports were identified relating to adult men taking oral sildenafil, tadalafil, vardenafil, or avanafil for sexual dysfunction. The most common adverse drug reactions included poor drug efficacy (42.5%), headache (10.4% vs. 8.5%-27.6% [Food and Drug Administration]), abnormal vision (8.4% vs. ≤4.6% [Food and Drug Administration]), flushing (5.2% vs. 5.1%-16.5% [Food and Drug Administration]), and dyspepsia (4.2% vs. 3.4%-11.1% [Food and Drug Administration]). Priapism showed significant signals for sildenafil (reporting odds ratio = 13.81, 95% confidence interval: 11.75-16.24), tadalafil (reporting odds ratio = 14.54, 95% confidence interval: 11.56-18.06), and vardenafil (reporting odds ratio = 14.12, 95% confidence interval: 8.36-22.35). Comparing with other medications in VigiBase, sildenafil (reporting odds ratio = 8.73, 95% confidence interval: 7.63-9.99) and tadalafil (reporting odds ratio = 4.25, 95% confidence interval: 3.19-5.55) had significantly higher reporting odds ratios for malignant melanoma.. Phosphodiesterase type 5 inhibitors show significant signals correlating with priapism among a large international cohort. Further clinical study is needed to elucidate whether this is from proper or inappropriate use or other confounding conditions, as analysis of pharmacovigilance data does not allow for quantifying the clinical risk. Also, there appears to be a relationship between phosphodiesterase type 5 inhibitor use and malignant melanoma, which warrants additional study to better understand causation.

Topics: Adolescent; Adult; Erectile Dysfunction; Humans; Male; Melanoma; Melanoma, Cutaneous Malignant; Pharmacovigilance; Phosphodiesterase 5 Inhibitors; Priapism; Sildenafil Citrate; Tadalafil; Vardenafil Dihydrochloride; World Health Organization

Topics: Chromatography, High Pressure Liquid; Chromatography, Liquid; Dietary Supplements; Erectile Dysfunction; Humans; Male; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Tadalafil; Tandem Mass Spectrometry; Vardenafil Dihydrochloride

In recent years, there has been an increase in the use of phosphodiesterase type 5 inhibitors (PDE5i) that are purchased from abroad without a doctor's diagnosis via the Internet or other means. We report six cases in which nonprescription use of PDE5i may have led to death. Among the four deceased individuals who were believed to have experienced sudden cardiac death, three (cases 1-3) had a history of cardiovascular disease, which is a contraindication, and the remaining case (case 4) involved combined use of multiple PDE5i. Sildenafil (0.063 µg/mL, 0.087 µg/mL) was detected in two of the four cases of sudden cardiac death. Tadalafil (0.096 µg/mL) was detected in one of the remaining two cases, and tadalafil (0.197 µg/mL) and vardenafil (0.011 µg/mL) were detected in the other case. Sildenafil (0.032 µg/mL), tadalafil (0.062 µg/mL), and ethanol were detected in a traffic accident case with a history of contraindications. In a case of asphyxiation by vomit aspiration, autopsy showed 90% stenosis in the anterior descending branch of the coronary artery, and sildenafil (0.063 µg/mL) was detected. To the best of our knowledge, this is the first report of postmortem blood levels of tadalafil and vardenafil likely contributing to the cause of death. Despite all the warnings about the dangers of using PDE5 inhibitors, cases of PDE5i contributing to death are still identified during autopsies. Therefore, raising public awareness of the risks of the risks associated with the imported drug use by individuals is necessary.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Contraindications, Drug; Death, Sudden, Cardiac; Erectile Dysfunction; Forensic Medicine; Humans; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Risk; Sexual Behavior; Sildenafil Citrate; Tadalafil; Vardenafil Dihydrochloride

This article discusses the physiological mechanisms of erection and the pathophysiological basis of erectile dysfunction. Parameters characterizing the features of the pharmacokinetics and pharmacodynamics of drugs from the group of phosphodiesterase type 5 inhibitors (PDE-5i) are presented. The clinical efficacy and possible adverse effects of the most significant PDE-5i are considered. These include sildenafil, tadalafil, vardenafil, udenafil, avanafil. There are also data on less known PDE-5i, which include lodenafil and mirodenafil.

Topics: Erectile Dysfunction; Humans; Male; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Tadalafil; Vardenafil Dihydrochloride

While phosphodiesterase type-5 inhibitors (PDE5Is) are highly effective for the treatment of erectile dysfunction (ED) and well tolerated, updated data on prescription patterns have been limited in real-world settings.. To describe men in the United States who are prescribed PDE5Is for ED treatment and to evaluate patterns of initiation, switching, and treatment overlap.. This retrospective claims study used MarketScan Commercial and Medicare Supplement Databases from January 1, 2010, to December 31, 2015, to identify initial PDE5I claims (index date) for sildenafil, tadalafil, and/or vardenafil. Adults aged ≥18 years with ED were identified between July 1, 2010, and December 31, 2014, allowing for a 6-month preindex and 12-month follow-up period from the index date.. Outcomes included patient demographics and treatment-related patterns after treatment initiation.. A total of 106,206 identified patients met all inclusion criteria. Of these, 51,694, 40,193, and 14,319 had initial claims for sildenafil, tadalafil, and vardenafil, respectively. Mean age was 50.35 years, and comorbidities included dyslipidemia (44.17%), hypertension (43.09%), diabetes (15.32%), and depression (10.61%). More patients (48.67%) initiated on sildenafil than tadalafil (37.85%) or vardenafil (13.48%). Rate of switching was lower in the 60 days after the end of day supply of the initial prescription in the sildenafil cohort (2.71%) compared with the tadalafil (2.81%) and vardenafil (3.88%) cohorts (P < .001 for sildenafil vs tadalafil or vardenafil). Treatment overlap was lower in the sildenafil cohort (0.35%) than in the tadalafil (0.75%) and vardenafil (0.62%) groups (P < .001 for sildenafil vs tadalafil or vardenafil).. These findings provide insight into updated patterns of PDE5I prescriptions in the United States and may aid in clinical decision-making.. Strengths include the large sample size, long data coverage period, and the real-world nature of the study. Limitations include the retrospective study design, use of data collected with a primary focus of claims, and lack of further details regarding reasons that drive switching. Actual rates of ED and impact on prescription patterns may be underestimated because the claims database only captured patients electing to visit a health-care provider.. Among men with ED in the United States, rates of switching and treatment overlap were low for all PDE5Is but were found to be the lowest for sildenafil compared with tadalafil and vardenafil. Mulhall JP, Chopra I, Patel D, et al. Phosphodiesterase Type-5 Inhibitor Prescription Patterns in the United States Among Men With Erectile Dysfunction: An Update. J Sex Med 2020;17:941-948.

Topics: Adult; Aged; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Medicare; Middle Aged; Phosphodiesterase 5 Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Prescriptions; Purines; Retrospective Studies; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; United States; Vardenafil Dihydrochloride

We report that two widely-used drugs for erectile dysfunction, tadalafil and vardenafil, trigger bone gain in mice through a combination of anabolic and antiresorptive actions on the skeleton. Both drugs were found to enhance osteoblastic bone formation in vivo using a unique gene footprint and to inhibit osteoclast formation. The target enzyme, phosphodiesterase 5A (PDE5A), was found to be expressed in mouse and human bone as well as in specific brain regions, namely the locus coeruleus, raphe pallidus, and paraventricular nucleus of the hypothalamus. Localization of PDE5A in sympathetic neurons was confirmed by coimmunolabeling with dopamine β-hydroxylase, as well as by retrograde bone-brain tracing using a sympathetic nerve-specific pseudorabies virus, PRV152. Both drugs elicited an antianabolic sympathetic imprint in osteoblasts, but with net bone gain. Unlike in humans, in whom vardenafil is more potent than tadalafil, the relative potencies were reversed with respect to their osteoprotective actions in mice. Structural modeling revealed a higher binding energy of tadalafil to mouse PDE5A compared with vardenafil, due to steric clashes of vardenafil with a single methionine residue at position 806 in mouse PDE5A. Collectively, our findings suggest that a balance between peripheral and central actions of PDE5A inhibitors on bone formation together with their antiresorptive actions specify the osteoprotective action of PDE5A blockade.

Topics: Aging; Animals; Bone and Bones; Bone Density; Brain; Cell Differentiation; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Repositioning; Erectile Dysfunction; Humans; Male; Mice; Middle Aged; Models, Animal; Models, Molecular; Neurons; Osteoblasts; Osteoclasts; Osteogenesis; Osteoporosis; Osteoporotic Fractures; Phosphodiesterase 5 Inhibitors; Primary Cell Culture; Tadalafil; Vardenafil Dihydrochloride

Infertility is a global health problem with about 15 percent of couples involved. About half of the cases of infertility are related to male-related factors. A major cause of infertility in men is oxidative stress, which refers to an imbalance between levels of reactive oxygen species (ROS) and antioxidants. Erectile dysfunction drugs (EDD), known as phosphodiesterase inhibitors (PDEIs), have been used for the treatment of ED. It has been shown that oxidative stress plays an important role in the progression of erectile dysfunction. Oxidative stress can be alleviated or decreased by non-antioxidants and antioxidant enzymes. The present study was undertaken to determine if these compounds could have a role in the incidence of infertility, especially after long-term use. Therefore, the present study aims to investigate the effect of EDD on the activities of antioxidant enzymes, free radical levels as well as the protein expression of different cytochrome P450 isozymes involved in the steroidogenesis of different hormones. In addition, the activity of both 17β-hydroxysteroid dehydrogenase and 17-ketosteroid reductase were assayed. The architectures of both livers and testes cells were investigated under the influence of EDD.. A daily dose of Sildenafil (1.48 mg/kg), Tadalafil (0.285 mg/kg) and Vardenafil (0.285 mg/kg) were administered orally to male rabbits for 12 week. Western immunoblotting, ELISA, spectrophotometric and histopathological techniques were used in this study.. The present study showed that Sildenafil, Vardenafil, and Tadalafil treatments significantly decreased the levels of glutathione and free radicals in both livers and testes of rabbits. Also, Vardenafil and Sildenafil induced the activity of superoxide dismutase and catalase whereas, glutathione S-transferase, glutathione reductase, and glutathione peroxidase activities inhibited in livers of rabbits. The protein expression of cytochrome P450 isozymes (CYP 11A1, 21A2, and 19C) which are involved in the steroidogenesis was markedly changed in both livers and testes of rabbits after their treatments for 12 weeks. After the treatment of rabbits with these medication, the protein expression of CYP11A1 was slightly down-regulated in both livers and testes except Sildenafil up-regulated such protein expression. In addition, the protein expressions of CYP11A1 and CYP 19C in both livers and testes were down-regulated after treatment of rabbits with Sildenafil, Vardenafil, and Tadalafil for 12 weeks. Also, these drugs inhibited the activity of both 17β-hydroxysteroid dehydrogenase and 17-ketosteroid reductase in testes of rabbits. Moreover, Sildenafil, Vardenafil, and Tadalafil-treated rabbits showed a decrease in spermatocytes and the number of sperms in the testes.. It is concluded that ED drugs induced the activities of both SOD and catalase which consequently decreased MDA level. Decrement in MDA levels and oxidative stress could therefore sustain the erection for a long period of time. On the other hand, it is not advised to use these drugs for a long-term since the protein expressions of CYP isozymes involved in steroidogenesis as well as the numbers of spermatocytes in testes were decreased.

Topics: Animals; Antioxidants; Cytochrome P-450 Enzyme System; Erectile Dysfunction; Glutathione; Isoenzymes; Liver; Male; Oxidative Stress; Rabbits; Sildenafil Citrate; Steroids; Tadalafil; Testis; Thiobarbituric Acid Reactive Substances; Vardenafil Dihydrochloride

The possible role of phosphodiesterase 5 inhibitors (PDE5Is) in prevention of negative effect of diabetes mellitus (DM) on erectile function is not well settled.. To investigate the effect of early administration of vardenafil on erectile function, cavernosal structure, and genes expression in a rat model of DM.. This experimental study was carried out at Suez Canal University's research laboratory. This study was conducted on a total of 60 adult male Albino Wistar rats, aged 60-80 days and weighing an average of 200 g. Rats were equally divided into six groups of 10 rats each: Group I (sham); Group II (DM with no treatment); Groups III, IV, V, and VI received vardenafil started at day 1, week 4, week 8, and week 12 after induction of DM, respectively. Functional study assessment of all groups was performed before euthanization, and then tissues were harvested for histopathological, ultrastructural, and molecular examinations.. There was a significant difference of intracavernosal pressure between early (94 ± 2.18) and late (40.5 ± 1.94) treatment groups (p = 0.011). Histopathological and ultrastructural changes of DM with no treatment and late treatment groups showed distorted cavernous architecture and extensive fibrosis. There was significant difference of smooth muscle to collagen ratio between early and late treatment groups (p = 0.035). There was significant upregulation of nNOS(p = 0.021) and iNOS (p = 0.047) in early vs. late treatment group. The difference was insignificant in eNOS (p = 0.386) or TGF-β1(p = 0.149).. Early treated rats with vardenafil had preserved erection and normal cavernosal structure, ultrastructure and gene expression of iNOS, nNOS, eNOS, and TGF-β1. Quantification of gene expression would improve our knowledge regarding cytokines expression and molecular background of DM-associated ED. Clinical application of this result may encourage early administration of PDE5I to prevent deleterious effects of DM on erectile function in newly diagnosed DM patients with probable uncontrolled blood glucose.

Topics: Animals; Diabetes Mellitus, Experimental; Drug Evaluation, Preclinical; Erectile Dysfunction; Male; Penis; Phosphodiesterase 5 Inhibitors; Rats, Wistar; Vardenafil Dihydrochloride

Diabetic mellitus erectile dysfunction (DMED) refers to erectile dysfunction (ED) secondary to diabetes. As people's lifestyle changes and the population ages, the incidence of DMED continues to increase. Many clinical trials have proven that PDE5-inhibitors-vardenafil has a significant effect in the treatment of Diabetic mellitus erectile dysfunction. In this systematic review, we aim to evaluate the effectiveness and safety of PDE5-inhibitors-vardenafil for Diabetic mellitus erectile dysfunction.. We will search PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to February 2019.We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of Diabetic mellitus erectile dysfunction.. This systematic review will evaluate the efficacy and safety of PDE5-inhibitors-vardenafil for treating Diabetic mellitus erectile dysfunction. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process Trial.. PROSPERO CRD42018095185.

Topics: Diabetes Complications; Erectile Dysfunction; Humans; Male; Meta-Analysis as Topic; Phosphodiesterase 5 Inhibitors; Systematic Reviews as Topic; Vardenafil Dihydrochloride

The widespread use of phosphodiesterase-5 inhibitors has attracted broad attention of counterfeiters to develop illicit erectile products with inaccurate amounts, unknown toxicity, and purity of active ingredients. Correspondingly, intake of these products endangers consumer health and needs to be screened for precautionary actions to reduce this risk. Therefore, in this study, a sensitive and rapid analytical method has been developed for simultaneous determination of selected phosphodiesterase-5 inhibitors present in illicit erectile medications and human urine. Quantification of the analytes was performed by liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry system. The chromatographic separation was successfully achieved with a run period of 8 min. Low detection limits were obtained in the range of 1.63-9.81 ng/g with relative standard deviations below 7.72% obtained using the replicate measurements of lowest concentration in calibration plots. The analytical performance of the proposed method proved good linearity, low detection limits, good accuracy and precision with high percent recoveries for human urine samples. Developed method was successfully applied to real samples including four different brands of illicit erectile medications. The results obtained revealed the presence of high levels of sildenafil in analyzed samples. The behaviors of selected phosphodiesterase-5 inhibitors were also studied in simulated gastric conditions.

Topics: Chromatography, Liquid; Erectile Dysfunction; Humans; Illicit Drugs; Male; Pyrimidines; Sildenafil Citrate; Stomach; Tadalafil; Tandem Mass Spectrometry; Vardenafil Dihydrochloride

Spending on direct-to-consumer advertising (DTCA) for prescription pharmaceuticals has risen to record levels, five times as much as in 1996 in inflation-adjusted dollars. Major health care provider organizations have called for additional regulation of DTCA. These organizations argue that the negative impact of such advertising outweighs the informational value claimed by the pharmaceutical industry. The industry maintains that further restrictions on DTCA are not warranted because it is successfully self-regulating via "guiding principles" for DTCA as certified by firm executives.. The authors measured recent industry spending on DTCA and used regression models of Nielsen Monitor-Plus data to assess pharmaceutical firm self-regulation after the public disclosure of noncompliance with industry self-regulatory principles, specifically regarding the exposure of children and adolescents to broadcast advertisements for erectile dysfunction drugs.. Public disclosure of noncompliance with self-regulatory DTCA standards did not bring advertising into compliance. Results demonstrate that firms failed to meet the industry standard during every quarter of the six-year period of this study.. Results support previous research findings that pharmaceutical self-regulation is a deceptive blocking strategy rather than a means for the industry to police itself. Policy recommendations include broadcast restrictions on adult content and deincentivizing DTCA via tax reform.

Topics: Adolescent; Child; Direct-to-Consumer Advertising; Drug Industry; Erectile Dysfunction; Guideline Adherence; Guidelines as Topic; Humans; Male; Prescription Drugs; Sildenafil Citrate; Tadalafil; Vardenafil Dihydrochloride; Vasodilator Agents

Western cultural perceptions that favour spontaneous sex may create unrealistic expectations for erectile dysfunction (ED) treatment. Little is known about how users of phosphodiesterase type 5 inhibitors (PDE5Is) plan sexual activity and timing of their preactivity PDE5I ingestion. Because various PDE5Is vary in their duration of action and dosage regimen, this may be an important consideration in selecting the optimal agent for the ED patient.. To better understand the sexual habits of PDE5I users.. Men from 7 countries (Brazil, China, Italy, Japan, Russia, Taiwan, Turkey) were screened online for age, self-reported comorbidities and ED medication use in the prior 3 months. After screening, eligible participants were asked to complete a 7-question, self-administered online survey containing questions regarding sexual habits and behaviours.. Survey questions focused primarily on advanced planning of sexual intercourse and timing of PDE5I ingestion but also addressed the frequency of sexual intercourse and ED medication use.. Of the 1458 respondents (response rate: 48%; median age: 48 years [interquartile range (IQR), 44-55]), 83% always/sometimes planned a specific time for intercourse in advance; 72% planned a specific time for sexual intercourse up to several hours in advance. Of respondents who planned in advance, more than half planned specific days of the week (55%) and times of the day (60%) for sexual intercourse. The time to sexual intercourse after dosing was ≤1 hour for 70% and ≤4 hours for 96% of men. The median frequency of sexual intercourse was 6 times/month (IQR, 4-10), with ED medication taken a median of 5 times/month (IQR, 3-8).. Sexual activity is usually planned by ED medication users several hours in advance, and the vast majority are attempting activity within a short time after ingestion of the agent. These data should aid clinicians in the selection of the optimal PDE5I.

Topics: Adult; Aged; Brazil; China; Coitus; Drug Administration Schedule; Erectile Dysfunction; Habits; Humans; Italy; Japan; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Russia; Sildenafil Citrate; Surveys and Questionnaires; Tadalafil; Taiwan; Time Factors; Turkey; Vardenafil Dihydrochloride

Vardenafil is a selective phosphodiesterase-5 inhibitor used for erectile dysfunction treatment. The hepatoprotective role of vardenafil against acute hepatitis is not reported yet. Hence, this study aims to explore the protective role of vardenafil against concanavalin A (Con A) induced acute liver injury. Mice were pretreated with vardenafil (0.17 mg/kg/day) for seven consecutive days, and then subjected to a single IV injection of Con A. The results demonstrated that the vardenafil pretreatment significantly reduced the elevated serum levels of transaminases and alkaline phosphatase. Histopathological examination showed marked necrosis and inflammation in Con A-treated mice which was significantly ameliorated in vardenafil pretreated animals. Vardenafil pretreatment significantly alleviated the expression of nuclear factor kappa-B and inducible nitric oxide synthase in the hepatic tissue. Additionally, serum levels of nitric oxide and tumor necrosis factor-alpha were decreased in vardenafil pretreated animals compared to the Con A group. Therefore, our results demonstrate that vardenafil has hepatoprotective effect and this could be linked to decrease inflammatory mediators.

Topics: Alkaline Phosphatase; Animals; Concanavalin A; Disease Models, Animal; Erectile Dysfunction; Hepatitis; Inflammation; Liver; Male; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Transaminases; Tumor Necrosis Factor-alpha; Vardenafil Dihydrochloride

To evaluate the expression of the Rho/Rho-associated protein kinase (ROCK) pathway in the corpus cavernosum of patients with severe erectile dysfunction (ED) compared with healthy human corpus cavernosum, and to test the functional effects of two Rho kinase inhibitors (RKIs) on erectile tissue of patients with severe ED, which did not respond to phosphodiesterase type 5 inhibitors (PDE5Is).. Human corpus cavernosum samples were obtained after consent from men undergoing penile prosthesis implantation (n = 7 for organ bath experiments, n = 17 for quantitative PCR [qPCR]). Potent control subjects (n = 5) underwent penile needle biopsy. qPCR was performed for the expression of RhoA and ROCK subtypes 1 and 2. Immunohistochemistry staining against ROCK and α smooth muscle actin (αSMA) was performed on the corpus cavernosum of patients with ED. Tissue strips were precontracted with phenylephrine and incubated with 1 μm of the PDE5I vardenafil or with DMSO (control). Subsequently, increasing concentrations of the RKIs azaindole or Y-27632 were added, and relaxation of tissue was quantified.. The expression of ROCK1 was unchanged (P > 0.05), while ROCK2 (P < 0.05) was significantly upregulated in patients with ED compared with controls. ROCK1 and ROCK2 protein colocalized with αSMA, confirming the presence of this kinase in cavernous smooth muscle cells and/or myofibroblasts. After incubation with DMSO, 10 μm azaindole and 10 μm Y-27632 relaxed precontracted tissues with 49.5 ± 7.42% (P = 0.1470 when compared with vehicle) and 85.9 ± 10.3% (P = 0.0016 when compared with vehicle), respectively. Additive effects on relaxation of human corpus cavernosum were seen after preincubation with 1 μm vardenafil.. The RKI Y-27632 causes a significant relaxation of corpus cavernosum in tissue strips of patients with severe ED. The additive effect of vardenafil and Y-27632 shows that a combined inhibition of Rho-kinase and phosphodiesterase type 5 could be a promising orally administered treatment for severe ED.

Topics: Amides; Drug Synergism; Enzyme Inhibitors; Erectile Dysfunction; Humans; Male; Middle Aged; Penis; Phosphodiesterase 5 Inhibitors; Pyridines; rho-Associated Kinases; Treatment Failure; Vardenafil Dihydrochloride

Topics: Amides; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Male; Penile Erection; Phosphodiesterase 5 Inhibitors; Pyridines; rho-Associated Kinases; Vardenafil Dihydrochloride

We evaluate the correlation between the plasma level of C-reactive protein (CRP) in patients with erectile dysfunction (ED) and hypertension and to set up whether the CRP level affected by the treatment of vardenafil 10 mg orally once daily. A total of 116 male patients with ED and hypertension were enrolled in this prospective study. The patients were divided into two groups, group 1 (ED patients with Not controlled hypertension) and group 2 (ED patients with controlled hypertension). All patients completed the International Index of Erectile Function (IIEF) scores, performed a penile color Doppler ultrasound examination and high sensitivity (hs-CRP) levels. The patients were given vardenafil 10 mg once daily for 3 months and reassessed again. According to the IIEF-EF domain score, there were statistically significant differences between the two groups (P=0.012) with a median value 10.0 (4.0-14.5) and 15.0 (9.0-16.5) between group 1 and group 2, respectively. Regarding to the severe (score<11), moderate (score 11-16) and mild (score 17-25) there were statistically significant differences between the two groups (0.023), (0.001) and (0.001), respectively. The hs-CRP showed statistically significant difference between the two groups (P=0.050) with a median value 2.4 (1.5-3.1) and 1.8 (1.1-2.4) between group 1 and group 2, respectively. The peak systolic velocity (PSV) and end diastolic velocity (EDV) showed statistically significant differences between the two groups (P=0.011) and (P=0.046), respectively. After treatment, there were improvements in the IIEF-EF domain score, severe (score<11), moderate (score 11-16), mild (score 17-25), PSV and EDV in both groups and these improvement were more obvious in (group 2) than (group 1) with a statistically significant differences between the two groups (P<0.05) (except in moderate (score 11-16), no statistically significant difference). The hs-CRP showed statistically significant differences between the two groups after treatment (P=0.049) with a median 2.1 (1.6-2.9) and 1.2 (0.9-2.4) between group 1 and group 2, respectively. Serum hs-CRP was significantly elevated in patients with ED and not controlled hypertension than in ED patients with controlled hypertension. ED patients with controlled blood pressure gave better results with penile duplex than those with not controlled blood pressure. Serum hs-CRP level could be a marker for an endothelial condition in men with ED and hypertension.

Topics: Adult; Aged; C-Reactive Protein; Case-Control Studies; Egypt; Erectile Dysfunction; Humans; Hypertension; Male; Middle Aged; Penile Erection; Prospective Studies; Severity of Illness Index; Vardenafil Dihydrochloride; Vasodilator Agents

A rapid onset of action for phosphodiesterase type 5 inhibitors (PDE5is) emerged to be of clinical importance in men treated for erectile dysfunction (ED). Data from randomized clinical trials (RCTs) showed a rapid onset of action for vardenafil 10 mg orodispersible tablet (ODT). However, the effectiveness of vardenafil ODT has never been tested in a real-life setting. We assessed the efficacy and time to onset of action of vardenafil ODT in men seeking medical help for ED in the everyday real-life clinical practice.. Patients completed a baseline and follow-up International Index of Erectile Function (IIEF), along with a 8-item self-administered questionnaire about onset of action and overall treatment outcomes. Descriptive statistics tested efficacy rates, patient timing of drug intake and time to post-dosing onset of action.. Overall, 118(59.9%) patients used vardenafil ODT. Satisfactory erections for vaginal penetration were reported in 39(34.5%) and 26(21.8%), patients in =15 and =30, minutes post-dosing, respectively. Minimal Clinically Important Differences (MCIDs) criteria and Yang's criteria for responders were obtained in 80(67.8%) and 72(60.8%) patients.. This study showed that one in three patients had satisfactory erection for vaginal penetration in less than 15 min post-dosing in the real-life setting.

Topics: Adult; Aged; Aged, 80 and over; Erectile Dysfunction; Humans; Male; Middle Aged; Penile Erection; Phosphodiesterase 5 Inhibitors; Surveys and Questionnaires; Tablets; Time Factors; Treatment Outcome; Vardenafil Dihydrochloride; Young Adult

Topics: Diabetes Mellitus, Type 2; Endothelium, Vascular; Erectile Dysfunction; Humans; Hypogonadism; Inflammation; Male; Vardenafil Dihydrochloride

Topics: Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Penile Erection; Prospective Studies; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Topics: Diabetes Mellitus, Type 2; Double-Blind Method; Erectile Dysfunction; Humans; Hypogonadism; Imidazoles; Inflammation; Male; Prospective Studies; Treatment Outcome; Vardenafil Dihydrochloride

Topics: Animals; Binding Sites; Computer Simulation; Drug Monitoring; Erectile Dysfunction; Isotope Labeling; Male; Metabolic Clearance Rate; Molecular Docking Simulation; Phosphodiesterase 5 Inhibitors; Protein Binding; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Technetium; Theranostic Nanomedicine; Tissue Distribution; Vardenafil Dihydrochloride

Erectile dysfunction (ED) is a major health problem and is mainly associated with the persistent inability of men to maintain sufficient erection for satisfactory sexual performance. Millions of men are using sildenafil, vardenafil, and/or tadalafil for ED treatment. Cytochrome P450s (CYPs) play a central role in the metabolism of a wide range of xenobiotics as well as endogenous compounds. Susceptibility of individuals to the adverse effects of different drugs is mainly dependent on the expression of CYPs proteins. Therefore, changes in activities of phase I drug-metabolising enzymes [arylhydrocarbon hydroxylase (AHH), dimethylnitrosamine N-demethylase (DMN-dI), 7-ethoxycoumarin-O-deethylase (ECOD), and ethoxyresorufin-O-deethylase ((EROD)] and the protein expression of different CYPs isozymes (CYP1A2, CYP2E1, CYP2B1/2, CYP3A4, CYP2C23, and CYP2C6) were determined after treatment of male rats with either low or high doses of sildenafil (Viagra), tadalafil (Cialis), and/or vardenafil (Levitra) for 3 weeks. The present study showed that low doses of tadalafil and vardenafil increased DMN-dI activity by 32 and 23%, respectively. On the other hand, high doses of tadalafil, vardenafil, and sildenafil decreased such activity by 50, 56, and 52%, respectively. In addition, low doses of tadalafil and vardenafil induced the protein expression of CYP2E1. On the other hand, high doses of either tadalafil or sildenafil were more potent inhibitors to CYP2E1 expression than vardenafil. Moreover, low doses of both vardenafil and sildenafil markedly increased AHH activity by 162 and 247%, respectively, whereas high doses of tadalafil, vardenafil, and sildenafil inhibited such activity by 36, 49, and 57% and inhibited the EROD activity by 39, 49, and 33%, respectively. Low and high doses of tadalafil, vardenafil, and sildenafil inhibited the activity of NADPH-cytochrome c reductase as well as its protein expression. In addition, such drugs inhibited the expression of CYP B1/2 along with its corresponding enzyme marker ECOD activity. It is concluded that changes in the expression and activity of phase I drug-metabolising enzymes could change the normal metabolic pathways and might enhance the deleterious effects of exogenous as well as endogenous compounds.

Topics: Animals; Cytochrome P-450 CYP2J2; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Drug Interactions; Erectile Dysfunction; Isoenzymes; Liver; Male; Metabolic Detoxication, Phase I; Phosphodiesterase 5 Inhibitors; Rats; Risk Assessment; Sildenafil Citrate; Tadalafil; Vardenafil Dihydrochloride

Erectile dysfunction (ED) is a common male sexual disorder worldwide. Three oral phosphodiesterase type 5 inhibitors (PDE5Is) - sildenafil, tadalafil and vardenafil - are available for treatment of ED. This study quantitatively evaluated the therapeutic efficacy and safety of these medications to assist treatment decision making.. We used multiple criteria decision analysis (MCDA) to assess the totality of risk-benefit of PDE5Is. We created two models: (i) the overall model included 'overall improvement in erections' and 'any adverse events' and (ii) the detailed model included 'erectile function domain', 'ability for sexual intercourse', 'duration of erection last', 'serious adverse events', 'headache', 'flushing' and 'dyspepsia'. We calculated a synthetic utility for each drug accounting for all of its benefits and risks.. Considering the overall risk-benefit, vardenafil had the highest synthetic utility among three medications; in the order of synthetic utilities: vardenafil (0.568), tadalafil (0.478) and sildenafil (0.437). However, when specific risk and benefit criteria were assessed, tadalafil had the highest synthetic utility (0.602) according to the conjoint evaluation (synthetic utility for vardenafil is 0.491 and sildenafil is 0.442, respectively). The sensitivity analysis based on the uncertainties of weight on risks of any adverse events (including serious adverse events and headache) suggested our results were robust.. This study provides a useful approach that comprehensively and systematically assesses and compares the risk-benefit of several treatment alternatives. Our study not only rank treatment alternatives by synthetic utilities based on the risk-benefit balance but also compare specific risk and benefit criteria between these medicines. Our results provide valuable evidence that can guide clinicians and patients in making treatment decisions.

Topics: Adult; Aged; Erectile Dysfunction; Humans; Male; Middle Aged; Penile Erection; Phosphodiesterase 5 Inhibitors; Risk Assessment; Sildenafil Citrate; Tadalafil; Vardenafil Dihydrochloride

To evaluate the predictability of vardenafil success in patients with erectile dysfunction (ED) by using cardiological tests.. Patients diagnosed with ED who did not benefit from lifestyle changes (n = 68) were evaluated with an abridged 5-item version of the International Index of Erectile Function (IIEF-5). The pretreatment and posttreatment IIEF-5 scores were compared with pretreatment data obtained from cardiological examinations.. When pretreatment scores were compared with test parameters, mitral flow E/A ratio and tissue Doppler imaging (TDI) E'/ A', exercise test duration, exercise capacity in MET, and percentage of maximum heart rate were found to be statistically significant. Furthermore, there was a significant negative correlation between mitral flow E/A ratio, TDI E'/A', exercise test duration, exercise capacity in MET, and the difference in post- and pretreatment IIEF-5 scores.. As a diastolic function indicator, TDI E'/A' positively correlates with pretreatment IIEF-5 scores and negatively correlates with the beneficial effect of vardenafil treatment. As a result, the cardiological status of the patient correlates with individual IIEF-5 scores, and it seems to be useful in predicting vardenafil success.

Topics: Biological Availability; Cardiovascular System; Drug Monitoring; Echocardiography, Doppler; Erectile Dysfunction; Heart Rate; Humans; Imidazoles; Male; Middle Aged; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Predictive Value of Tests; Statistics as Topic; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Vesicular drug delivery systems have recently gained attention as a way of improving dosing accuracy for drugs with poor transdermal permeation. The current study focuses on utilization of the natural biocompatible vesicles to formulate vardenafil nanoethosomes (VRD-NE), for the enhancement of their transdermal permeation and bioavailability. Fifteen formulations were prepared by thin-layer evaporation technique according to Box-Behnken design to optimize formulation variables. The effects of lipid composition, sonication time, and ethanol concentration on particle size and encapsulation efficiency were studied. The diffusion of vardenafil (VRD) from the prepared nanoethosomes specified by the design was carried out using automated Franz diffusion cell apparatus. The optimized formula was investigated for in vivo pharmacokinetic parameters compared with oral VRD suspension. Confocal laser scanning microscopy images were used to confirm enhanced diffusion release of VRD in rat skin. The results showed that the optimized formula produced nanoethosomes with an average size of 128 nm and an entrapment efficiency of 76.23%. VRD-NE provided a significant improvement in permeation with an enhancement ratio of 3.05-fold for a film made with optimally formulated VRD-NE compared with a film made with VRD powder. The transdermal bioavailability of VRD from the nanoethosome film was approximately twofold higher than the oral bioavailability from an aqueous suspension. VRD-NE thus provide a promising transdermal drug delivery system. As a result, management of impotence for a longer duration could be achieved with a reduced dosage rate that improves patient tolerability and compliance for the treatment of erectile dysfunction.

Topics: Administration, Cutaneous; Animals; Biological Availability; Diffusion; Drug Carriers; Drug Delivery Systems; Erectile Dysfunction; Male; Particle Size; Rats; Skin Absorption; Surface Properties; Vardenafil Dihydrochloride

A method was established for rapid screening and quantifying 11 illegally added anti-impotence preparations (yohimbine, acetildenafil, nor-acetildenafil, homosildenafil, hydroxy-homosildenafil, sildenafil, vardenafil, thioaildenafil, tadalafil, pseudovardenafil, dapoxetine) in health care products by high performance liquid chromatography-high resolution mass spectrometry. The samples were extracted with methanol and analyzed by positive mode in the MS detection. The results showed that the limits of detection were 25.0 ng/mLexcept for nor-acetildenafil (5.0 ng/mL), the linear ranges were 5.0-200.0 ng/mL except for nor-acetildenafil (25.0-500.0 ng/mL) with the correlation coefficients not less than 0.999 0. The recoveries were in the range of 82.0%-105.9% with the relative standard deviations of 4.7%-16.5%. This method is accurate, simple and rapid, and can be used in rapid screening and quantitative analysis of the 11 illegally added anti-impotence in health care products.

Topics: Benzylamines; Chromatography, High Pressure Liquid; Drug Contamination; Erectile Dysfunction; Humans; Indole Alkaloids; Male; Mass Spectrometry; Naphthalenes; Sildenafil Citrate; Tadalafil; Vardenafil Dihydrochloride; Vasodilator Agents

Many men with "late-onset hypogonadism" (LOH) experience lower urinary tract symptoms (LUTS) that can be distressing and may decrease quality of life. LUTS often appear in men when testosterone levels begin to decline, which could be a significant association. We investigated whether testosterone replacement could alleviate LUTS in men with LOH.. Two hundred and sixty-one hypogonadal patients (mean age 59.5 years) presenting with erectile dysfunction, having also been evaluated for LUTS, received a single testosterone undecanoate injection at day 1, at week 6 and quarterly thereafter. Parameters, including International Prostate Symptom Score (IPSS), post-voiding residual urine volume, transrectal ultrasound, prostate volume and prostate-specific antigen were measured at each treatment visit. Two hundred and fifty-nine patients were included in the full analysis set. These were subsequently divided into weight losers (L ≥ 5 % weight loss at last visit from baseline) and non-losers (NL). t test analyses were used to compare the IPSS means of these subgroups. The potentially confounding effect on IPSS of using the phosphodiesterase-5 inhibitor (PDE5i) vardenafil was also accounted for.. Mean IPSS showed a significant decrease with time following initiation of testosterone treatment (p < 0.05). No significant differences were observed in either IPSS between L and NL groups or in mean IPSS between vardenafil users and non-users.. Testosterone replacement is associated with improvements in LUTS which are not confounded by weight loss or PDE5i. The mechanisms of this association require further investigation.

Topics: Age of Onset; Aged; Erectile Dysfunction; Eunuchism; Hormone Replacement Therapy; Humans; Imidazoles; Longitudinal Studies; Lower Urinary Tract Symptoms; Male; Middle Aged; Piperazines; Prospective Studies; Registries; Sulfones; Testosterone; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

The role of testosterone in erectile dysfunction (ED) is increasingly recognized. It is suggested that assessment of testosterone deficiency in men with ED and symptoms of hypogonadism, prior to first-line treatment, may be a useful tool for improving therapy.. In this prospective, observational, and longitudinal study, we investigated the effects of vardenafil treatment as adjunctive therapy to testosterone undecanoate in hypogonadal ED patients who failed to respond to testosterone treatment alone.. One hundred twenty-nine testosterone deficient (serum total testosterone ≤ 3.4 ng/mL) patients aged 56 ± 3.9 years received intramuscular injections of long-acting parenteral testosterone undecanoate at 3-month intervals for 8 months mean follow-up.. Scores on the International Index of Erectile Function Questionnaire-five items (IIEF-5) and partner survey scores were compared at baseline and posttreatment with testosterone therapy alone or in combination with vardenafil. Patient baseline demographics and concomitant disease were correlated with patients' IIEF-5 scores.. Seventy one (58.2%) responded well to monotherapy within 3 months. Nonresponders had lower testosterone levels and higher rates of concomitant diseases and smoking. Thirty-four of the 51 nonresponders accepted the addition of 20 mg vardenafil on demand. Efficacy assessments were measured by the IIEF-erectile function domain (IIEF-EF, questions 1-5 plus 15, 30 points) and partner self-designed survey at baseline after 4-6 weeks and at study end point. Thirty out of 34 patients responded well to this combination. IIEF-EF Sexual Health Inventory for Men score improved from 12 to 24 (P < 0.0001), and partner survey showed significantly higher satisfaction (P < 0.001). These patients reported spontaneous or nocturnal and morning erections or tumescence. No changes in adverse effects were recorded.. These data suggest that combination therapy of testosterone and vardenafil is safe and effective in treating hypogonadal ED patients who failed to respond to testosterone monotherapy.

Topics: Aged; Aged, 80 and over; Drug Therapy, Combination; Erectile Dysfunction; Female; Humans; Hypogonadism; Imidazoles; Male; Middle Aged; Penile Erection; Personal Satisfaction; Piperazines; Prospective Studies; Sexual Partners; Sulfones; Testosterone; Triazines; Vardenafil Dihydrochloride

The United Kingdom is unusual in that a significant proportion of patients with erectile dysfunction (ED) have their treatment fully reimbursed by the National Health Service (NHS). This may have consequences for the choice of treatment and for compliance with treatment.. The aim of this study was to evaluate the use and cost implications of phosphodiesterase type 5 inhibitor in an NHS setting.. Basic demographics and data on ED management for patients treated from January 2000 to April 2011 were obtained from a prospectively accrued database. We reviewed drug usage and costs as well as switching between drugs. Patients were given the choice of all available therapies and were followed up annually.. Switching, compliance, and costs of treating ED under the "severe distress" criteria in the NHS were reviewed for this study.. Two thousand one hundred fifty-nine patients qualified for reimbursed therapy. Two hundred twenty-six patients were excluded from further analysis owing to missing data. Patients were followed up on an annual basis. The mean patient age was 60.2 years (min 23, max 90), and the mean follow-up was 50.8 months (min 1, max 127). Six hundred ninety-six were started on sildenafil, 990 on tadalafil, 163 on vardenafil, and 84 on intracavernosal alprostadil. Eighteen percent of patients initially started on the scheme and stopped medication unilaterally. Of the patients, 12.3% changed their medication during follow-up. The cost of drugs increased year by year from £257,100 in 2007 to £352,519 in 2011.. Our real-life observational study shows that in our institution, dropout of therapy is unusual. We hypothesize that this reflects, in part, the reimbursement issue. We also found that switching between drugs was unusual, although there are several possible explanations for that. Although this is a successful system for the patients, the hospital, which bears the costs of medication, is finding this an increasing economic drain.

Topics: Adult; Aged; Aged, 80 and over; Ambulatory Care; Carbolines; Drug Costs; Erectile Dysfunction; Humans; Imidazoles; Longitudinal Studies; Male; Middle Aged; Patient Compliance; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; State Medicine; Sulfones; Tadalafil; Triazines; United Kingdom; Vardenafil Dihydrochloride; Young Adult

This study assessed the improvement in relationship quality, effectiveness and safety associated with vardenafil for the treatment of erectile dysfunction (ED). The study was conducted in 1433 centres across 21 countries and comprised a baseline patient visit and up to four follow-up visits during an observational period of 1 year. Relationship quality, happiness, satisfaction with vardenafil treatment, and safety and tolerability were assessed by physician interviews and patient and partner questionnaires. Overall, 7496 patients were enrolled in the study, of which 7430 were included in the safety analyses and 6470 in the effectiveness analyses. Relationship quality, assessed by a relationship questionnaire (partnerschaftsfragebogen [PFB]), was improved at last observation carried forward, compared with baseline, in both patients and partners and satisfaction with the effectiveness of vardenafil treatment was high. Vardenafil was well tolerated and adverse events were consistent with the known safety profile of phosphodiesterase type 5 inhibitors. These results confirm the well-established effectiveness and safety profiles of vardenafil. This study is the first to demonstrate improvements in relationship quality following vardenafil therapy, in both patients and partners, using the PFB questionnaire.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase 5 Inhibitors; Piperazines; Prospective Studies; Quality of Life; Sexual Behavior; Sexual Partners; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Young Adult

A pathogenic link between erectile dysfunction (ED) and metabolic syndrome (MetS) is now well established. Nonalcoholic steatohepatitis (NASH), the hepatic hallmark of MetS, is regarded as an active player in the pathogenesis of MetS-associated cardiovascular disease (CVD). This study was aimed at evaluating the relationship between MetS-induced NASH and penile dysfunction. We used a non-genomic, high fat diet (HFD)-induced, rabbit model of MetS, and treated HFD rabbits with testosterone (T), with the selective farnesoid X receptor (FXR) agonist obeticholic acid (OCA), or with the anti-TNFα mAb infliximab. Rabbits fed a regular diet were used as controls. Liver histomorphological and gene expression analysis demonstrated NASH in HFD rabbits. Several genes related to inflammation (including TNFα), activation of stellate cells, fibrosis, and lipid metabolism parameters were negatively associated to maximal acetylcholine (Ach)-induced relaxation in penis. When all these putative liver determinants of penile Ach responsiveness were tested as covariates in a multivariate model, only the association between hepatic TNFα expression and Ach response was confirmed. Accordingly, circulating levels of TNFα were increased 15-fold in HFD rabbits. T and OCA dosing in HFD rabbits both reduced TNFα liver expression and plasma levels, with a parallel increase of penile eNOS expression and responsiveness to Ach. Also neutralization of TNFα with infliximab treatment fully normalized HFD-induced hypo-responsiveness to Ach, as well as responsiveness to vardenafil, a phosphodiesterase type 5 inhibitor. Thus, MetS-induced NASH in HFD rabbits plays an active role in the pathogenesis of ED, likely through TNFα, as indicated by treatments reducing liver and circulating TNFα levels (T or OCA), or neutralizing TNFα action (infliximab), which significantly improve penile responsiveness to Ach in HFD rabbits.

Topics: Acetylcholine; Animals; Antibodies, Monoclonal; Chenodeoxycholic Acid; Diet, High-Fat; Dietary Fats; Erectile Dysfunction; Fatty Liver; Gene Expression; Humans; Imidazoles; Infliximab; Liver; Male; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Penis; Phosphodiesterase 5 Inhibitors; Piperazines; Rabbits; Receptors, Cytoplasmic and Nuclear; Sulfones; Testosterone; Triazines; Tumor Necrosis Factor-alpha; Vardenafil Dihydrochloride

The efficacy of oral pharmacotherapy for erectile dysfunction (ED) (i.e., type 5 phosphodiesterase[PDE5] inhibitors) is significantly reduced in diabetic patients. Nebivolol is a selective β1-blocker used for treatinghy pertension that has been shown to increase the efficacy of sildenafil to reverse ED in diabetic rats.. To evaluate the effects of nebivolol on the efficacy of the PDE5 inhibitors, sildenafil, tadalafil, and vardenafil to relax human corpus cavernosum (HCC) and vasodilate human penile resistance arteries (HPRA) from diabetic patients with ED (DMED). The influence of nebivolol on the capacity of these three PDE5 inhibitors to stimulate cyclic guanosine monophosphate (cGMP) production in HCC was also evaluated.. HCC and HPRA were obtained from organ donors without ED (NEND; n = 18) or patients with diabetes undergoing penile prosthesis implantation (DMED; n = 19). Relaxations of HCC strips and HPRA to sildenafil,tadalafil, and vardenafil were evaluated in organ chambers and wire myographs. cGMP content in HCC was determined by ether extraction and quantification by ELISA.. Effects of nebivolol on PDE5 inhibitor-induced relaxation of HCC, vasodilation ofHPRA and cGMP accumulation in HCC.. Treatment with nebivolol (1 μM) significantly potentiated sildenafil-, tadalafil- and vardenafil-induced relaxations of HCC and vasodilations of HPRA from both NEND and DMED. Enhancement of relaxant capacity by nebivolol resulted in reversion of the impairment of PDE5 inhibition-induced responses in DMED and it was accompanied by enhancing the ability of PDE5 inhibitors to increase cGMP in HCC restoring reduced cGMP levelsin HCC from DMED.. Nebivolol potentiated the capacity of PDE5 inhibitors to relax vascular structures of erectile tissue from diabetic patients by enhancing the nitric oxide (NO)/cGMP pathway in these tissues. These effects suggest a potential therapeutic utility of nebivolol as an adjunct to PDE5 inhibitors for the treatment of ED associated with diabetes.

Topics: Arteries; Benzopyrans; Carbolines; Cyclic GMP; Diabetes Mellitus, Type 2; Drug Synergism; Erectile Dysfunction; Ethanolamines; Humans; Imidazoles; Male; Middle Aged; Muscle Relaxation; Muscle, Smooth, Vascular; Nebivolol; Nitric Oxide; Penile Erection; Penis; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Topics: Aged; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Life Style; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Pyrimidines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Overall efficacy rates of phosphodiesterase type 5 inhibitors (PDE5-i) for erectile dysfunction (ED) are 60-70%. PDE5-i treatment failures currently have to resort to invasive treatment options for restoration of erectile function. AIMS.: To assess changes in the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase (PKG) pathway in human corpus cavernosum (HCC) of PDE5-i nonresponders compared with healthy controls. To evaluate the effects of BAY 60-4552, a stimulator of soluble guanylate cyclase (sGC), and vardenafil on relaxation of HCC strips from PDE5-i nonresponders.. mRNA expression, morphological localization of the NO/cGMP/PKG pathway, and relaxant capacity of both compounds alone or combined. Analysis of variance, t-test or Mann-Whitney test based upon number of groups and normality of data.. HCC tissues were harvested after consent from individuals undergoing penile prosthesis implantation (patients) and potent patients undergoing transurethral surgery (healthy controls, needle biopsy). HCC tissues of patients were compared with those of healthy controls for the expression of mRNA coding for PDE5A, eNOS, PKGα1, PKG2, sGCα1, sGCα2, sGCβ1, sGCβ2, α-smooth muscle actin (aSMA) and β-actin by quantitative polymerase chain reaction (qPCR). The respective proteins were localized using immunofluorescence. Tissue strips of patients were precontracted with phenylepinephrine followed by incubation with 1 μM of either vardenafil or BAY 60-4552, or both simultaneously.. The main targets in the NO/cGMP/sGC pathway were downregulated in PDE5-i nonresponders. The pathway was morphologically located to HCC smooth muscle, of which the overall content was preserved in ED patients based on aSMA expression. BAY 60-4552 and vardenafil have synergistic effects on relaxation of HCC of PDE5-i nonresponders. The main limitation is the small amount of control tissue precluding functional testing on these samples.. Despite downregulation of the NO/cGMP/PKG pathway, combining BAY 60-4552 with vardenafil significantly enhanced relaxation HCC strips of PDE5-i nonresponders.

Topics: Actins; Cyclic GMP; Drug Synergism; Erectile Dysfunction; Guanylate Cyclase; Humans; Imidazoles; Male; Middle Aged; Muscle, Smooth; Penile Erection; Penis; Phosphodiesterase 5 Inhibitors; Piperazines; Pyrazoles; Pyrimidines; Receptors, Cytoplasmic and Nuclear; Soluble Guanylyl Cyclase; Sulfones; Triazines; Vardenafil Dihydrochloride

Cross-sectional analysis of electronic medical and pharmacy records.. To examine associations between use of medication for erectile dysfunction or testosterone replacement and use of opioid therapy, patient age, depression, and smoking status.. Males with chronic pain may experience erectile dysfunction related to depression, smoking, age, or opioid-related hypogonadism. The prevalence of this problem in back pain populations and the relative importance of several risk factors are unknown.. We examined electronic pharmacy and medical records for males with back pain in a large group model health maintenance organization during 2004. Relevant prescriptions were considered for 6 months before and after the index visit.. There were 11,327 males with a diagnosis of back pain. Males who received medications for erectile dysfunction or testosterone replacement (n = 909) were significantly older than those who did not and had greater comorbidity, depression, smoking, and use of sedative-hypnotics. In logistic regressions, the long-term use of opioids was associated with greater use of medications for erectile dysfunction or testosterone replacement compared with no opioid use (odds ratio, 1.45; 95% confidence interval, 1.12-1.87, P < 0.01). Age, comorbidity, depression, and use of sedative-hypnotics were also independently associated with the use of medications for erectile dysfunction or testosterone replacement. Patients prescribed daily opioid doses of 120 mg of morphine-equivalents or more had greater use of medication for erectile dysfunction or testosterone replacement than patients without opioid use (odds ratio, 1.58; 95% confidence interval, 1.03-2.43), even with adjustment for the duration of opioid therapy.. Dose and duration of opioid use, as well as age, comorbidity, depression, and use of sedative-hypnotics, were associated with evidence of erectile dysfunction. These findings may be important in the process of decision making for the long-term use of opioids.. 4.

Topics: Adult; Age Factors; Aged; Analgesics, Opioid; Androgens; Back Pain; Carbolines; Comorbidity; Cross-Sectional Studies; Depression; Drug Prescriptions; Erectile Dysfunction; Hormone Replacement Therapy; Humans; Imidazoles; Insurance, Health; Logistic Models; Male; Middle Aged; Piperazines; Prevalence; Purines; Sildenafil Citrate; Smoking; Sulfones; Tadalafil; Testosterone; Triazines; United States; Urological Agents; Vardenafil Dihydrochloride

To assess persistence/adherence rates of phosphodiesterase type-5 inhibitor (PDE5I) on-demand dosing in Latin American men with erectile dysfunction (ED), and explore patient characteristics and treatment factors that may be predictive for PDE5I persistence and adherence.. Men from Brazil, Mexico, and Venezuela with ED who were naïve to PDE5Is were prescribed sildenafil, tadalafil, vardenafil, or lodenafil on-demand dosing and asked to provide information about PDE5I use at baseline and at 1, 3, and 6 months. Patients were persistent if they used ≥1 dose during the 4 week period prior to each evaluation. Patients were adherent if they complied with dosing instructions during most recent dose. Main outcome measures included Persistence and Adherence Questionnaire (PAQ), Partner Relationship Questionnaire (PRQ), Self-Esteem and Relationship (SEAR) Questionnaire, and International Index of Erectile Function (IIEF). Multivariate logistic regression was used to identify factors associated with persistence and adherence.. A total of 511 men were enrolled; most had mild to moderate ED (77.1%); 317 patients (62.0%) were prescribed tadalafil, 116 (22.7%) sildenafil, 75 (14.7%) vardenafil, and 3 (0.6%) lodenafil (not further analyzed). A total of 340 patients (66.5%) were 'persistent' at 6 months; 345 (67.5%) were 'adherent'. Persistence and adherence were associated with age, education level, and ED duration. Reasons for non-persistence included medication cost and lack of efficacy. Study limitations included its design, brief observation period, its bias observed toward tadalafil selection; its dependence on patient self-reporting, limited number of factors that were analyzed for persistence/adherence association, its small number of participating patients and Latin American countries, and inherent differences in PDE5I preference and medical practices.. Approximately two-thirds of PDE5I-naïve, Latin American men with ED were persistent and adherent after 6 months of therapy. Factors like education level, ED severity, and ED duration were associated with persistence and adherence; additional study is warranted to investigate the predictive value of these factors.

Topics: Carbolines; Carbonates; Erectile Dysfunction; Humans; Imidazoles; Latin America; Male; Medication Adherence; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Prospective Studies; Purines; Pyrimidines; Self Concept; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) negatively impacts quality of life. Phosphodiesterase type 5 inhibitors (PDE5Is) are effective in treating ED; however, rates of discontinuation remain high.. To assess on-demand PDE5I treatment persistence and adherence through 6 months in Middle Eastern and North African (MENA) men with ED in a prospective, non-interventional, observational trial.. Enrolled men were ≥18 years old from Saudi Arabia, Egypt, and the United Arab Emirates, PDE5I naïve, and sexually active. PDE5Is were selected per routine clinical practice. Persistence was defined as use of ≥1 dose during the prior 4 weeks, adherence as compliance with dosing instructions during the most recent dose. Logistic regression models were used to identify factors associated with persistence and adherence.. Persistence and Adherence Questionnaire; Partner Relationship Questionnaire; Self-Esteem and Relationship Questionnaire; International Index of Erectile Function (IIEF); Erectile Dysfunction Inventory of Treatment Satisfaction.. Patients' (n = 493) mean age was 49.8 years, mean BMI was 29.3, and the majority (n = 354, 71.8%) were from Saudi Arabia. Tadalafil was the most prescribed PDE5I (69.6%), versus sildenafil (15.4%), or vardenafil (15.0%). Patients' mean IIEF-Erectile Function scores improved from moderate to mild and Erection Hardness Scores (SD) improved from 1.8 (1.0) at baseline to 3.5 (0.7) at 6 months. At 6 months, 64.9% of patients were treatment persistent (tadalafil, 68.8%, sildenafil, 65.8%, and vardenafil, 45.9%) and 59.6% were adherent. Factors significantly predictive (p < 0.05) of persistence at 6 months included age, employment status, and ED severity. Factors significantly predictive of adherence were age, employment status, and duration of ED. Interpretation of differences between drugs was limited by substantial differences in prescription rates between countries.. At 6 months, 64.9% of men were treatment persistent. In this study, age, employment status, ED severity, and duration of ED were associated with persistence and/or adherence.

Topics: Carbolines; Egypt; Erectile Dysfunction; Humans; Imidazoles; Male; Medication Adherence; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Prospective Studies; Purines; Saudi Arabia; Self Concept; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Tadalafil; Treatment Outcome; Triazines; United Arab Emirates; Vardenafil Dihydrochloride

The purpose of this study was to explore attitudes about condoms that may affect condom use by heterosexual men ages 50 and older who were sexually active and currently using prescribed oral phosphodiesterase type 5 inhibitor medications (Viagra(®), Cialis(®), or Levitra(®)) for treatment of erectile dysfunction. The study was part of a larger study that explored the need for safer-sex health promotion and education for these men. Fifty men completed factor subscales of the Condom Attitude Scale. Subscales were scored and analyzed. Positive factors were found with regard to the Interpersonal Impact, Inhibition, Perceived Risk, Perceived Seriousness, and Global Attitudes subscales. Factors with negative or neutral responses included the Effect on Sexual Experience, Relationship Safety, and Promiscuity subscales. Independent t tests revealed no differences between married and nonmarried men for the mean score on any of the subscales, but there was a difference on the Global Attitude Scale, with younger men having a more positive global attitude than older men. Study findings can be used in the development of health promotion educational activities on condom use as a safer-sex practice.

Topics: Carbolines; Condoms; Erectile Dysfunction; Female; Health Behavior; Health Promotion; Heterosexuality; Humans; Imidazoles; Male; Middle Aged; Piperazines; Purines; Safe Sex; Sexual Partners; Sexually Transmitted Diseases; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Great attention has been paid to the clinical significance of phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, tadalafil, and vardenafil widely used for erectile dysfunction. However, sildenafil causes side effects on visual functions since it shows similar potencies to inhibit PDE5 and PDE6, whereas tadalafil gives a high selectivity of 1020-fold against PDE6. Till now, their molecular mechanisms of selectivity of PDE5 versus PDE6 have remained unknown in the absence of the crystal structure of PDE6. In order to elucidate its isoform-selective inhibitory mechanism, a 3D model of PDE6 was constructed by homology modeling, and its interaction patterns with tadalafil plus sildenafil were exploited by molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations. The present work reveals that tadalafil exhibits a less negative predicted binding free energy of -35.21 kcal/mol with PDE6 compared with the value of -41.12 kcal/mol for PDE5, which suggests that tadalafil prefers PDE5 rather than PDE6 and confers a high selectivity for PDE5 versus PDE6. The binding free energy results for tadalafil were consistent with external bioassay studies (IC50 = 5100 and 5 nM toward PDE6 and PDE5, respectively). Two important residues from the Q2 pockets (Val782 and Leu804 in PDE5 and their corresponding Val738 and Met760 in PDE6) were further identified to account for the high selectivity of tadalafil for PDE5 versus PDE6. These findings have shed light on the continuous puzzle of why sildenafil (IC50 = 74 and 6 nM toward PDE6 and PDE5, respectively) causes visual disorders because of its poor selectivity but tadalafil does not. In addition, the homology model of PDE6 can be used to design more potent and selective second-generation PDE5 inhibitors with less inhibitory potency against PDE6.

Topics: Binding Sites; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Cyclic Nucleotide Phosphodiesterases, Type 6; Erectile Dysfunction; Humans; Imidazoles; Ligands; Male; Molecular Docking Simulation; Molecular Dynamics Simulation; Phosphodiesterase 5 Inhibitors; Piperazines; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Purines; Sildenafil Citrate; Structural Homology, Protein; Sulfones; Tadalafil; Thermodynamics; Triazines; Urological Agents; Vardenafil Dihydrochloride

To evaluate phosphodiesterase type 5 (PDE5) inhibitors in the management of temporary penile erectile dysfunction (ED) in patients undergoing assisted reproductive technology (ART).. This study included 75 male patients that experienced ejaculation failure due to temporary ED during ART treatment. We treated the patients with PDE5 inhibitors sildenafil, tadanafil and vardenafil, and then evaluated the hardness of penile erection using Erection Hardness Score (EHS) and analyzed the end-point efficacy.. Sildenafil was administered to 28 of the patients, tadanafil to 25, and vardenafil to 22. Of the total number of patients, 61 (81.3%) achieved effective erection, but no significant differences were observed in the rate of effectiveness among the sildenafil (24 cases, 85.7%), tadanafil (20 cases, 80.0%) and vardenafil (17 cases, 77.3%) groups (P > 0.05). After medication, 53 (70.7%) of the patients successfully ejaculated, but there were no remarkable differences in the success rate among the sildenafil (21 cases, 75.0%), tadanafil (17 cases, 68.0%) and vardenafil (15 cases, 68.2%) groups (P > 0.05). Of the 75 patients, 37 received the recommended initial dose and 38 the maximum recommended dose of PDE5 inhibitors, but no significant differences were found in the rate of successful sperm retrieval between the former (28 cases, 75.7%) and the latter group (25 cases, 65.8%) (P > 0.05). Mild adverse events, including transient flush and dizziness, occurred in 5 cases (6.7%).. PDE5 inhibitors can help temporary ED patients to achieve penile erection and ejaculation during ART treatment.

Topics: Ejaculation; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Reproductive Techniques, Assisted; Sildenafil Citrate; Sulfonamides; Sulfones; Triazines; Vardenafil Dihydrochloride

We investigated the effect angiotensin II (Ang II), a corpus cavernosal smooth muscle (CCSM) constrictor peptide, has on tissue taken from rabbits following chronic partial bladder outlet obstruction (PBOO), as this model is characterized by an increase in corpus cavernosal collagen deposition and a marked reduction and impaired relaxation of CCSM cells.. To determine the interaction between Ang II and nitric oxide (NO) and the development of oxidative stress (OS) in a rabbit model of chronic PBOO.. Corpus cavernosal tissue was obtained from 12 sham-operated and 20 PBOO rabbits. Organ bath studies determined Ang II/NO interaction on CCSM function using losartan (AT1 receptor antagonist), sodium nitroprusside (SNP, NO donor), electrical field stimulation (EFS), and vardenafil (phosphodiesterase type 5 inhibitor). The role of OS in the Ang II response was also determined using diphenylene iodonium chloride (DPI), the nicotinamide adenine dinucleotide phosphate oxidase inhibitor, which inhibits superoxide production and superoxide dismutase (SOD, the enzyme that accelerates the breakdown of superoxide).. Action of Ang II and AT1 receptor antagonist, as well as SOD and DPI on CCSM function.. Ang II caused a dose-dependent contraction of CCSM strips that was enhanced in PBOO rabbits and inhibited by losartan, DPI, and SOD. CCSM relaxation induced by SNP/EFS was impaired in this model and improved by vardenafil and losartan.. These findings imply that the increased Ang II contractile response is a pathological consequence of PBOO and that AT1 receptor inhibition may be a therapeutic approach to treat ED associated with PBOO.

Topics: Angiotensin II; Animals; Disease Models, Animal; Electric Stimulation; Erectile Dysfunction; Imidazoles; Male; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Nitric Oxide; Nitric Oxide Donors; Nitroprusside; Oxidative Stress; Penis; Phosphodiesterase 5 Inhibitors; Piperazines; Rabbits; Sulfones; Triazines; Urinary Bladder Neck Obstruction; Vardenafil Dihydrochloride

Utility of phosphodiesterase inhibitors (PDEi's) for the treatment of erectile dysfunction (ED) has been the focus of experimental and clinical studies. However, public preferences, attitudes, and experiences with PDEi's are rarely addressed from a population/epidemiology viewpoint. The Global Online Sexuality Survey (GOSS) is a worldwide epidemiologic study of sexuality and sexual disorders, first launched in the Middle East in 2010, followed by the United States in 2011.. To describe the utilization rates, trends, and attitudes toward PDEi's in the United States in the year 2011.. GOSS was randomly deployed to English-speaking male Web surfers in the United States via paid advertising on Facebook®, comprising 146 questions.. Utilization rates and preferences for PDEi's by brand.. Six hundred three subjects participated; mean age 53.43 years ± 13.9. Twenty-three point seven percent used PDEi's on more consistent basis, 37.5% of those with ED vs. 15.6% of those without ED (recreational users). Unrealistic safety concerns including habituation were pronounced. Seventy-nine point six percent of utilization was on prescription basis. PDEi's were purchased through pharmacies (5.3% without prescription) and in 16.5% over the Internet (68% without prescription). Nine point six percent nonprescription users suffered coronary heart disease. Prescription use was inclined toward sildenafil, generally, and particularly in severe cases, and shifted toward tadalafil in moderate ED and for recreational use, followed by vardenafil. Nonprescription utilization trends were similar, except in recreational use where sildenafil came first.. In the United States unrealistic safety concerns over PDEi's utility exist and should be addressed. Preference for particular PDEi's over the others is primarily dictated by health-care providers, despite lack of guidelines that govern physician choice. Online and over-the-counter sales of PDEi's are common, and can expose a subset of users to health risks. Recreational use of PDEi's is common, and could be driven by undiagnosed premature ejaculation.

Topics: Adult; Aged; Carbolines; Comorbidity; Coronary Artery Disease; Cross-Sectional Studies; Drug Administration Schedule; Drug Utilization; Erectile Dysfunction; Health Surveys; Humans; Illicit Drugs; Imidazoles; Internet; Male; Middle Aged; Nonprescription Drugs; Phosphodiesterase Inhibitors; Piperazines; Prescription Drugs; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; United States; Vardenafil Dihydrochloride

To ensure public safety all Food and Drug Administration (FDA)-approved medications undergo postapproval safety analysis. Phosphodiesterase type-5 inhibitors (PDE5-i) are generally regarded as safe and effective.. We performed a nonindustry-sponsored analysis of FDA reports for sildenafil, tadalafil, and vardenafil to evaluate the reported cardiovascular and mortality events over the past 10 years.. Summarized reports of adverse events (AEs) for each PDE5-i were requested from the Center for Drug Evaluation and Research within the FDA. These data are available under the Freedom of Information Act and document industry and nonindustry reports of AEs entered into the computerized system maintained by the Office of Surveillance and Epidemiology.. The data were analyzed for the number of AE reports, number of objective cardiovascular events, and reported deaths.. Overall, 14,818 AEs were reported for sildenafil. There were 1,824 (12.3%) reported deaths, and reports of cardiovascular AEs numbered 2,406 (16.2%). Tadalafil was associated with 5,548 AEs and 236 deaths were reported. Vardenafil was associated with 6,085 AEs and 121 reports of deaths. The percentage of reported severe cardiovascular disorders has stabilized at 10% to 15% of all AE reports for sildenafil and tadalafil and 5% to 10% for vardenafil. Only 10% of AE reports sent to the FDA for PDE5-i were from pharmaceutical manufacturers.. Reports of deaths associated with PDE5-i remain around 5% of total reported events. Despite inherent limitations from evaluating FDA reports of AEs, it is important that these reports be reviewed outside pharmaceutical industry support in order to provide due diligence and transparency. Lowe G and Costabile RA. 10-year analysis of adverse event reports to the Food and Drug Administration for phosphodiesterase type-5 inhibitors. J Sex Med 2012;9:265-270.

Topics: Carbolines; Cardiovascular Diseases; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Product Surveillance, Postmarketing; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; United States; United States Food and Drug Administration; Vardenafil Dihydrochloride

Rare cases of central serous chorioretinopathy (CSC) associated with the intake of sildenafil citrate have been reported, although CSC is not included in the list of phosphodiesterase 5 (PDE5) inhibitor side effects.. We present a review of the literature and 2 cases of CSC in 2 men taking PDE5 inhibitors (vardenafil and tadalafil) for erectile dysfunction. In both cases chorioretinopathy appeared after intake of the inhibitor, resolved once the latter was discontinued, reappeared when the inhibitor was restarted and resolved once again after the inhibitor had been discontinued for the second time.. PDE5 inhibitors used for male erectile dysfunction have been associated with ocular side effects including lid edema, hyposphagma, photophobia, mydriasis, dyschromatopsia, and nonarteritic anterior ischemic optic neuropathy. CSC was previously described in patients taking sildenafil citrate. Very recently, a case of CSC after tadalafil intake was reported. The relevant literature is reviewed and possible pathophysiologic mechanisms are discussed.. The 2 presented cases of CSC after intake of vardenafil or tadalafil with positive dechallenge, rechallenge and second dechallenge reactions provide important arguments for considering CSC as a rare PDE5 inhibitor class-specific side effect.

Topics: Aged; Carbolines; Central Serous Chorioretinopathy; Erectile Dysfunction; Fluorescein Angiography; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Sulfones; Tadalafil; Tomography, Optical Coherence; Triazines; Vardenafil Dihydrochloride; Vision Disorders

Several methods have been so far proposed to compare the effectiveness of the three available phosphodiesterase type 5 inhibitors (PDE5Is).. Two urologists (E.C. and G.B.B.), together with the Controversy's Editor (E.A.J.), with expertise in the area of medical treatment of erectile dysfunction (ED) present the various perspectives on the evaluation of PDE5Is in ED. The use of the most popular psychometric tool, the International Index of Erectile Function, is presented by an expert psychologist (L.R.D.).. Expert opinion supported by the critical review of the currently available literature.. Trials have demonstrated that the PDE5Is are excellent drugs with a great specificity of action and an almost perfect tolerance profile. Some instruments for comparison of clinical efficacy have to be considered subjective (psychometry, patient's preference, changes in quality of general, or sexual life). Some others are more objective (hardness, hormonal levels, and local circulation). An evidence-based comparison of the three PDE5Is should in the future be rooted in both subjective and objective methods. This will be of paramount importance in the drug trial design of new, forthcoming PDE5Is.. Comparison between PDE5Is using both subjective and objective parameters will permit to individuate, on the basis of the evidence, the subset of couples where one drug, or one dose, or dose regimen, is to be considered of first choice.

Topics: Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Penile Erection; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

There is a high prevalence of erectile dysfunction (ED) in men with epilepsy; however, few studies have been conducted concerning the treatment of ED in this neurological group.. The main purpose of this review is to highlight the influence of phosphodiesterase type 5 inhibitor (PDEI-5) for ED on seizure susceptibility.. All available online articles with information pertaining to PDEI-5 and seizure susceptibility were included in this review.. The main outcome assessed demonstrated the intriguing role of PDEI-5 and its metabolites on seizure susceptibility.. Case reports in men without epilepsy described seizure occurrence and electrophysiological changes following sildenafil, tadalafil, or vardenafil treatment. Consistent with these findings, preclinical studies suggested a proconvulsant effect of PDEI-5 on models of seizure induction.. Evidence suggests an influence of PDEI-5 on seizure susceptibility in humans. In addition, preclinical studies have demonstrated the role of nitric oxide metabolites in the facilitation of paroxysmal phenomenon. Although there are many causes of seizures, medical professionals should be aware of the possible influence of PDEI-5 on seizure susceptibility. Further investigation by physicians and scientists is required to improve our understanding of this important topic.

Topics: Aged; Animals; Carbolines; Disease Susceptibility; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Prevalence; Purines; Rats; Seizures; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

We investigated the in vitro inhibitory effects of avanafil, a novel, potent inhibitor of phosphodiesterase-5, on 11 phosphodiesterases. We also studied its potentiation of penile tumescence in dogs.. Phosphodiesterase assay was done with the 4 phosphodiesterase-5 inhibitors avanafil, sildenafil, vardenafil and tadalafil using 11 phosphodiesterase isozymes. In anesthetized dogs the pelvic nerve was repeatedly stimulated to evoke tumescence. Intracavernous pressure was measured after avanafil or sildenafil administration.. Avanafil specifically inhibited phosphodiesterase-5 activity at a 50% inhibitory concentration of 5.2 nM. Avanafil showed higher selectivity (121-fold) against phosphodiesterase-6 than sildenafil and vardenafil (16 to 21-fold) and showed excellent selectivity (greater than 10,000-fold) against phosphodiesterase-1 compared with sildenafil (375-fold). Avanafil also had higher selectivity against phosphodiesterase-11 than tadalafil (greater than 19,000 vs 25-fold). Avanafil also showed excellent selectivity against all other phosphodiesterases. After intravenous administration in anesthetized dogs the 200% effective dose of avanafil and sildenafil on the penile tumescence was 37.5 and 34.6 μg/kg, respectively. After intraduodenal administration the 200% effective dose of avanafil and sildenafil on tumescence was 151.7 and 79.0 μg/kg at the peak time, respectively. Time to peak response with avanafil and sildenafil was 10 and 30 minutes, respectively, indicating a more rapid onset of avanafil.. Avanafil has a favorable phosphodiesterase-5 selectivity profile compared to that of marketed phosphodiesterase-5 inhibitors. Avanafil shows excellent in vitro and in vivo potency, and fast onset of action for penile erection. Cumulative data suggest that avanafil has a promising pharmacological profile for erectile dysfunction.

Topics: Animals; Carbolines; Dogs; Dose-Response Relationship, Drug; Erectile Dysfunction; Humans; Imidazoles; Infusions, Intravenous; Male; Penile Erection; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Pyrimidines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Phosphodiesterase type 5 (PDE5) inhibitors are indicated for the treatment of erectile dysfunction (ED); however, they can also inhibit other PDE isozymes, affecting their target tissues (e.g., PDE1: heart; PDE6: retina; and PDE11: skeletal muscle), which in some cases can cause unwanted side effects and therapy discontinuation. Data from in vitro studies showed that avanafil, a PDE5 inhibitor for the treatment of ED, exhibited strong selectivity toward PDE5 and against all other PDE isozymes.. To review the inhibitory effects of avanafil for PDE isozymes compared with those of sildenafil, tadalafil, and vardenafil and to discuss these results within the context of clinical trial safety observations.. Review of in vitro selectivity data for avanafil (published primary data from a peer-reviewed journal and scientific congress abstracts); PubMed search for pertinent publications on PDE5 inhibitor safety data; and review of published articles and abstracts from avanafil phase 1, 2, and 3 clinical trials.. A low incidence of some PDE-related adverse events may be reflected by the high selectivity of avanafil against non-PDE5 isozymes.. Avanafil is highly selective toward PDE5 and against all other PDE isozymes tested. Lower selectivity against PDE1, PDE6, and PDE11 is consistent with results from randomized, placebo-controlled, phase 3 trials in which musculoskeletal and hemodynamic adverse events were reported in <2% of patients and no color vision-related abnormalities were reported with avanafil doses up to 200 mg once daily.. Data suggest that avanafil may confer a safety benefit, in terms of a lower incidence of specific adverse events, by virtue of its high specificity to PDE5 and its overall selectivity against other PDE isozymes.

Topics: Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Penile Erection; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Pyrimidines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Eruptions from drugs are among the most frequently reported adverse events. The most frequent etiologic agents include antibiotics and nonsteroidal anti-inflammatory agents. These eruptions are also a frequent source of visits to dermatology of!ces. Many of the inciting agents are known and have been well described. Frequently implicated drugs include antibiotics, nonsteroidal antiinflammatory medications, and anticonvulsants. This case report reviews a drug eruption that has not yet been noted, despite years of experience with the class of drug involved in this case, and the literature associated with it.

Topics: Aged; Anti-Infective Agents, Local; Drug Eruptions; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Skin; Steroids; Sulfones; Triazines; Vardenafil Dihydrochloride

MEGATON, a dietary supplement, was analyzed in order to detect PDE-5 inhibitors and their analogues. A new analogue of vardenafil could be detected by high-performance liquid chromatography (HPLC) analysis with a photodiode array detector (PDA). This compound was compared with sildenafil, tadalafil, and vardenafil as well as their structurally modified analogues such as hongdenafil and homosildenafil. The structure of this compound was elucidated by mass spectrometry (MS), infrared (IR) spectroscopy and one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy. When compared with vardenafil to verify the structural difference, this compound had an acetyl group instead of a sulfonyl group in the pyrazolopyrimidine portion without any substitution in the piperazine ring of the molecule. This compound was identified as 2-(2-ethoxy-5-(2-(4-ethylpiperazin-1-yl)acetyl)phenyl)-5-methyl-7-propyl-imidazo(5,1-f)-(1,2,4)triazin-4(3H)-one, which is also called acetylvardenafil.

Topics: Carbolines; Chromatography, Liquid; Dietary Supplements; Drug Contamination; Erectile Dysfunction; Humans; Imidazoles; Magnetic Resonance Spectroscopy; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Saccharomyces cerevisiae; Sildenafil Citrate; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Infrared; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

To compare the cost-effectiveness of four, six, and eight doses per month of vardenafil in the context of pharmacy benefit decision making.. A Markov model was used to estimate the incremental cost-effectiveness of zero, four, six, or eight doses of vardenafil per month in hypothetical cohorts of 60-year-old male veterans with erectile dysfunction. Efficacy values for vardenafil were obtained from the literature, and vardenafil costs were obtained from Veterans Affairs pharmacy data. The analysis was conducted from a third-party payer perspective with a lifetime horizon, and the effect of parameter uncertainty was explored in one-way and probabilistic sensitivity analyses.. In the base case analysis, the cost per quality-adjusted life-year gained for four doses of vardenafil per month compared with no therapy was $576. Six doses per month compared with four cost $2585/quality-adjusted life-year gained, and eight doses per month compared with six cost $5169/quality-adjusted life-year gained. In one-way sensitivity analyses of six doses per month compared with four, variation of two parameters caused the incremental cost-effectiveness ratio to cross a willingness-to-pay threshold of $20,000: when the increased utility associated with giving two additional doses/month was less than 0.001 (baseline 0.01) and when the cost per dose increased to $15.00 (baseline $1.69).. Although four doses per month of vardenafil was the most cost-effective strategy, the use of six or eight doses per month also compares favorably with other accepted medical treatments. The results were stable across a range of inputs and help to support the current Veterans Affairs policy on the number of vardenafil doses provided per month for erectile dysfunction.

Topics: Adult; Aged; Aged, 80 and over; Cost-Benefit Analysis; Drug Administration Schedule; Drug Costs; Erectile Dysfunction; Humans; Imidazoles; Male; Markov Chains; Middle Aged; Models, Econometric; Phosphodiesterase 5 Inhibitors; Piperazines; Quality of Life; Quality-Adjusted Life Years; Sulfones; Triazines; Vardenafil Dihydrochloride; Veterans

Phosphodiesterase type 5 (PDE5) inhibitors are very effective agents for erectile dysfunction; however, specific patient populations are hard to treat. The efficacy of PDE5 inhibitors is limited because a minimum amount of nitric oxide (NO) is necessary. Resveratrol, a plant polyphenol, is reported to activate endothelial NO synthase (eNOS) through activation of sirtuin 1. We previously reported that human corpus cavernosal smooth muscle cells (CCSMCs) express eNOS and synthesize cyclic guanosine monophosphate (cGMP) via the NO/cGMP pathway.. To investigate the ability of resveratrol and/or vardenafil to increase cGMP in an in vitro model using CCSMCs and to improve erectile function in an in vivo rat model of streptozotocin (STZ)-induced diabetes.. CCSMCs were treated with resveratrol and/or vardenafil. Twenty male Sprague-Dawley rats were randomly divided into five groups (N = 4 in each group): age-matched controls, diabetic controls, and diabetic rats treated with resveratrol, vardenafil, or both in combination for the last 4 weeks of an 8-week period of diabetes induction.. Intracellular cGMP measurement, intracovernous pressure (ICP)/mean arterial pressure (MAP) ratio, and smooth muscle/collagen ratio.. Intracellular cGMP level was elevated by resveratrol treatment in CCSMCs. The combination treatment of resveratrol and vardenafil had a synergistic effect. Diabetic rats showed impairment of erectile function. Treatment with either resveratrol or vardenafil improved ICP/MAP ratio, and combination therapy with resveratrol and vardenafil had a synergistic effect in improvement of ICP/MAP.. Treatment with either resveratrol or vardenafil elevated cGMP level in CCSMCs and improved erectile function in STZ-induced diabetic rats. Furthermore, a synergistic effect was observed in vitro and in vivo. Resveratrol or combination therapy of resveratrol and vardenafil can improve erectile function in which NO release is impaired, although further study is needed to confirm the results.

Topics: Animals; Antioxidants; Cyclic GMP; Diabetes Mellitus, Experimental; Erectile Dysfunction; Imidazoles; Male; Muscle, Smooth; Nitric Oxide; Nitric Oxide Synthase Type III; Penis; Phosphodiesterase 5 Inhibitors; Piperazines; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Sulfones; Triazines; Vardenafil Dihydrochloride

Radical prostatectomy (RP) is frequently responsible for erectile dysfunction (ED). Post-RP patients often show a failure to respond to phosphodiesterase type 5 (PDE5) inhibitors.. The acute effect of BAY 60-4552, the soluble guanylate cyclase (sGC) stimulator, and vardenafil were evaluated alone or in combination on erectile responses to electrical stimulation of the cavernous nerve (ES CN) in rats with cavernous nerve (CN) crush injury-induced ED.. Male adult Sprague-Dawley rats underwent laparotomy (sham, n=10) or bilateral CN crush injury (n=56). After 3 wk of recovery, erectile function was evaluated under urethane anaesthesia following ES CN at different frequencies.. The acute effects of intravenous (IV) injection of vehicle, vardenafil 0.03 mg/kg, BAY 60-4552 0.03 mg/kg or 0.3 mg/kg, or a BAY 60-4552 0.03 mg/kg plus vardenafil 0.03 mg/kg combination were evaluated in CN-crushed rats.. Bilateral CN crush injury followed by a 3-wk recovery period decreased erectile responses to ES CN by about 50%. In CN-crushed rats, IV vardenafil 0.03 mg/kg and BAY 60-4552 (0.03 or 0.3 mg/kg) increased erectile responses to ES CN to the same extent: Δ intracavernosal pressure/mean arterial pressure (ICP/MAP) at 10 Hz ES CN was 21±1% after vehicle, 25±3% (p<0.001) after vardenafil, and 26±5% and 27±5% after BAY 60-4552 0.03 mg/kg (p<0.01) and 0.3 mg/kg (p<0.001), respectively. The combination of vardenafil with BAY 60-4552 in CN-crushed rats totally restored erectile responses to ES CN equivalent to sham rats (ΔICP/MAP at 10 Hz ES CN: 34±4% after BAY 60-4552/vardenafil combination vs 39±4% in sham rats; not significant).. The present study supports the concept that the combined administration of a sGC stimulator, BAY 60-4552, and vardenafil provides synergistic beneficial effects and might therefore salvage patients who experience treatment failures with PDE5 inhibitors after RP.

Topics: Animals; Blood Pressure; Cyclic Nucleotide Phosphodiesterases, Type 5; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Electric Stimulation; Enzyme Activation; Enzyme Activators; Erectile Dysfunction; Guanylate Cyclase; Imidazoles; Male; Nerve Crush; Penis; Phosphodiesterase 5 Inhibitors; Piperazines; Pyrazoles; Pyrimidines; Rats; Rats, Sprague-Dawley; Receptors, Cytoplasmic and Nuclear; Soluble Guanylyl Cyclase; Sulfones; Time Factors; Treatment Failure; Triazines; Vardenafil Dihydrochloride

Topics: Animals; Enzyme Activators; Erectile Dysfunction; Imidazoles; Male; Penis; Phosphodiesterase 5 Inhibitors; Piperazines; Pyrazoles; Pyrimidines; Sulfones; Triazines; Vardenafil Dihydrochloride

To evaluate the efficacy and safety of long-term on-demand use of vardenafil in the treatment of erectile dysfunction (ED).. We conducted a questionnaire investigation among 891 ED patients treated by on-demand use of oral vardenafil at 20 mg every 3 days from March 2007 to January 2010, covering the general information of the patients, their need for and attitudes towards the treatment, clinical efficacy and adverse events of the drug, and satisfaction of the patients and their partners after 12 weeks of treatment.. Treatment and follow-up were completed in 700 patients, of whom 504 (72%) achieved sufficient hardness and duration of penile erection and overall sexual satisfaction, 84 (12%) admitted to improvement of erectile hardness and duration but not adequate satisfaction, and the other 112 (16%) experienced no significant changes. Significant differences were found in IIEF-5 scores, Rigiscan test results and partners TSS scores before and after the treatment (P < 0.05). Most frequent adverse events included flushing (15%), dizziness and headache (10%), dyspepsia (3%), and nasal congestion (1%).. Long-term on-demand use of oral vardenafil, in addition to its safety and good tolerance, can effectively improve the erectile function of ED patients, their success rate of sexual intercourse, and overall quality of sexual life.

Topics: Adult; Erectile Dysfunction; Follow-Up Studies; Humans; Imidazoles; Male; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents; Young Adult

The purpose of this study was to determine if there is an increased risk of central serous chorioretinopathy (CSC) associated with prescription exposure to phosphodiesterase-5 (PDE-5) inhibitors.. A case-control study linking 2 National Veterans Health Administration databases (clinical and pharmacy) for fiscal years 2004 to 2005. The likelihood of past exposure to PDE-5 inhibitors among newly diagnosed patients with CSC, identified through International Classification of Diseases, 9th Edition, Clinical Modification codes, was compared with 2 age-matched control groups after excluding subjects with risk factors for CSC.. Among 577 men, aged 59 years and younger with newly diagnosed CSC during the study year, 111 were prescribed a PDE-5 inhibitor (19.2%). The proportions of age-matched controls prescribed a PDE-5 inhibitor in the 2 groups were 18.5% and 21.5%. The odds ratio of exposure was 1.05 (95% confidence limit: 0.74-1.22) and 0.87 (95% confidence limit: 0.68-1.12).. Patients with CSC had no increase in prescription exposure to PDE-5 inhibitors than did age-matched control subjects. Although the findings in this study do not support an association between CSC and PDE-5 inhibitors, postmarketing surveillance methods for drug-related side effects have acknowledged limitations.

Topics: Adolescent; Adult; Carbolines; Case-Control Studies; Central Serous Chorioretinopathy; Databases, Factual; Drug Prescriptions; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Product Surveillance, Postmarketing; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; United States; United States Department of Veterans Affairs; Vardenafil Dihydrochloride; Young Adult

The phosphodiesterase type 5 (PDE-5) inhibitors-sildenafil, vardenafil, and tadalafil-are used primarily in erectile dysfunction, but sildenafil is also indicated for pulmonary hypertension. Common adverse effects of vardenafil include headache, flushing, nasal congestion, dyspepsia, and nausea. Recently, PDE-5 inhibitors have been associated with adverse vision effects, and emerging evidence now indicates that they may also be responsible for hearing changes and hearing loss. We describe a patient who developed unilateral sudden sensorineural hearing loss possibly related to the use of vardenafil for erectile dysfunction. To our knowledge, only one other case of hearing loss related to this drug class has been published. Our patient was a 57-year-old man who came to the emergency department with right-sided mild-to-moderate hearing loss in the 500-3000-Hz range, confirmed by audiogram, that occurred after ingestion of vardenafil. The patient was hospitalized 2 days later for administration of intravenous dexamethasone, followed by oral prednisone. He reported that his hearing had improved on the fourth hospital day and was discharged 3 days later, continuing to taper the prednisone on an outpatient basis. A repeat audiogram after 10 days of corticosteroid therapy confirmed that his hearing in the 500-3000-Hz range was within normal limits. Use of the Naranjo adverse drug reaction probability scale indicated a possible (score of 3) adverse reaction of sudden sensorineural hearing loss associated with vardenafil consumption. We also performed an analysis of hearing loss cases related to PDE-5 inhibitors in the United States Food and Drug Administration's Adverse Event Reporting System database to compare the characteristics of our patient with those of other reported adverse event cases. Based on the temporal relation of the sudden sensorineural hearing loss to this patient's drug consumption, we propose that the vardenafil is a likely cause of the hearing loss. This case provides further evidence that PDE-5 inhibitor consumption should be considered as a possible cause in patients presenting with sudden sensorineural hearing loss.

Topics: Erectile Dysfunction; Hearing Loss, Sudden; Hearing Loss, Unilateral; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

Topics: Blood Glucose; Carbolines; Cardiovascular Diseases; Cholesterol; Erectile Dysfunction; Humans; Imidazoles; Impotence, Vasculogenic; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Purines; Severity of Illness Index; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Tadalafil; Triazines; Vardenafil Dihydrochloride

Topics: Adrenergic alpha-Antagonists; Androgens; Carbolines; Diagnosis, Differential; Erectile Dysfunction; Humans; Imidazoles; Injections; Male; Penile Implantation; Penis; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vacuum; Vardenafil Dihydrochloride; Vasodilator Agents

The appearance of counterfeit medicines in supply chains is a global public health problem that may seriously affect patients. Counterfeit drugs do not meet quality standards and do not declare their real composition and/or source for the purposes of fraud. They may be generic or innovative, they may contain genuine constituents in a fake packaging, or wrong ingredients, or inactive ingredients, or an incorrect quantity of the active substance. In Croatia, no cases of counterfeit medicines have been detected so far, but the Agency for Medicinal Products and Medical Devices has received 34 samples of medicines and other products for testing from Zagreb City Police. The samples included medicines for erectile dysfunction: sildenafil, tadalafil, and vardenafil. Twenty-three samples of tablets without marketing authorisation in Croatia were tested with high-performance liquid chromatography (HPLC) for the declared sildenafil and tadalafil content. Samples labelled 1 (batch T/33), 3 (batch T/33), 5 (batch 4), 6 (batch M0016J), 10 (batch T-070235), 12 (batch T-070544), 15 (batch 314833201), 16 (batch 832718474), and 17 (batch 504830028) containing sildenafil and samples labelled 20 (batch 070356), 21 (batch 05668), and 22 (batch T 378 5) containing tadalafil did not contain the active substance within the acceptable 95 % to 105 % margin of deviation from the declared content. While most samples cannot be described as fake with a reasonable amount of certainty, there is still a suspicion of counterfeit. A correct conclusion can be drawn only with the assistance of the manufacturers and by conducting additional laboratory tests.

Topics: Carbolines; Chromatography, High Pressure Liquid; Croatia; Erectile Dysfunction; Fraud; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Estimate the proportion of phosphodiesterase type-5 inhibitor (PDE5-I) patients who co-possess nitrates and compare the proportion of tadalafil patients dispensed nitrates to a matched control group. Secondarily, examine the percentage of co-possession of PDE5-Is and nitrates where the products were dispensed on the same day or written by the same prescriber.. Male patients aged 18+ years filling PDE5-I prescriptions between December 2003 and March 2006 were identified using a U.S. longitudinal prescription database (IMS Health LRx). Similar patients not dispensed a PDE5-I during this period were matched to the tadalafil-dispensed cohort using a propensity score approach. Co-possession, as a proxy for concurrent use, was defined as an overlap in time on therapy for a PDE5-I and nitrate and was compared for the three PDE5-Is and for tadalafil to the matched control group.. Among 601,063 tadalafil patients, 3.31% were dispensed a nitrate during the study period, compared to 6.18% in control patients (n = 601,063). When co-possessed prescriptions were defined by overlapping exposure periods, the proportion of PDE5-I patients with co-possessed nitrates ranged from 1.44% (tadalafil) to 1.72% (vardenafil) and 2.13% (sildenafil). Co-possession percentages of PDE5-I prescriptions were 0.83% for tadalafil and 1.07% for sildenafil and vardenafil. The majority (54.29%) of co-possessed PDE5-I and nitrate prescriptions had the nitrate dispensed prior to the PDE5-I prescription identified in the study cohort.. Keeping in mind the limitations of observational studies, these results suggest that co-dispensing of nitrates and PDE5-Is is low. Compared to control patients, the proportion of nitrate co-possession was lowest for patients filling tadalafil. Tadalafil patients also had the lowest co-possessed proportion among the three PDE5-I cohorts. While the majority of co-possessed drug pairs were prescribed by different providers, the highest percentage of co-prescribing from the same physician was among cardiologists. These results suggest that physicians adhere to contraindications and are careful about co-prescribing of nitrates with PDE-5Is.

Topics: Adolescent; Adult; Aged; Carbolines; Databases, Factual; Drug Therapy, Combination; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Nitrates; Pharmaceutical Services; Phosphodiesterase Inhibitors; Piperazines; Practice Patterns, Physicians'; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Young Adult

A simple and sensitive method was developed for determination of illegal adulterants (yohimbine, sildenafil, vardenafil and tadalafil) in dietary supplements by HPLC-MS/MS. The separation was achieved on a C(18) column with the mobile phase consisting of acetonitrile and 0.1% acetic acid aqueous solution with a gradient elution at a flow rate of 0.5 mL/min. The analytes were quantified and identified by two characteristic transitions using the multiple-reaction monitoring mode. The recoveries of the analytes ranged from 77.5 to 109.3% with the RSD less than 8.1% (n=6). The method has been successfully applied to screen illegal adulterations of natural dietary supplements.

Topics: Adrenergic alpha-Antagonists; Carbolines; Chromatography, High Pressure Liquid; Dietary Supplements; Erectile Dysfunction; Humans; Imidazoles; Male; Molecular Structure; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Tandem Mass Spectrometry; Triazines; Vardenafil Dihydrochloride; Yohimbine

Sociopsychological factors play a critical role in the pathogenesis of erectile dysfunction (ED). An optimal therapeutic regimen is supposed to bring sociopsychological benefits to both the patients and their partners. Psychological and Interpersonal Relationship Scales (PAIRS) is an effective measure for evaluating the impact of ED on the psychological aspects and interpersonal relationship of the patients and their partners, as well as for predicting the satisfaction of ED patients with the treatment. PAIRS scores on the effects of phosphodiesterase type 5 inhibitors on ED show a significant decrease in sexual activity-related time concerns of the patients treated with tadalafil, as compared with those medicated with sildenafil or vardenafil. This also underlies the preference of the patients and their partners for tadalafil in clinical practice. The drug attribute associated with the decreased time concerns is the long and outstanding efficacy of tadalafil for up to 36 hours.

Topics: Carbolines; Erectile Dysfunction; Female; Humans; Imidazoles; Interpersonal Relations; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Time Factors; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

The Real-Life Safety and Efficacy of vardenafil study is an international, open-label, prospective, noncomparative, noninterventional study in men with erectile dysfunction (ED).. To determine the safety and efficacy of vardenafil in a large international pool of men with ED (aged ≥ 18 years) and associated underlying conditions (N=73,946), in a real-life setting.. Patients attended an initial physician visit and one to two follow-up visits. Data were acquired by physician interviews and patient diaries and recorded in case report forms (CRFs). Data were pooled from 47 countries in Europe, Asia-Pacific, Latin America, and the rest of the world (excluding the United States and Japan for methodological reasons). Results were stratified by baseline ED severity, body mass index (BMI), and the presence of hypertension, diabetes, lipid metabolism disorder, or cardiovascular disease (CVD).. CRFs and patient questionnaires containing questions on overall improvement of erection, satisfaction with efficacy, and desire to continue vardenafil use.. Many participants had hypertension (32.0%), diabetes (22.1%), lipid metabolism disorder (14.6%), or CVD (42.2%). High percentages of patients reported improvements in erectile function, irrespective of baseline ED severity (mild, 97.0%; moderate, 96.2%; severe, 85.5%), BMI (<25, 94.1%; ≥ 25 and <30, 94.6%; ≥ 30, 92.9%), or the presence of hypertension (93.6%), diabetes (92.6%), lipid metabolism disorder (94.7%), or CVD (93.3%). Over 90% of patients, including those with underlying conditions, reported being "satisfied" or "very satisfied" with vardenafil efficacy, and stated their intention to continue vardenafil use after the end of the study period. The incidence of adverse events was low, and 97.0% of patients were either "satisfied" or "very satisfied" with vardenafil tolerability.. These data from a worldwide population of men with ED and associated underlying conditions show that vardenafil is effective and well-tolerated for the treatment of ED in a real-life setting, supporting its use as a first-line ED therapy.

Topics: Cardiovascular Diseases; Diabetes Mellitus; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Lipid Metabolism Disorders; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase 5 Inhibitors; Piperazines; Product Surveillance, Postmarketing; Prospective Studies; Severity of Illness Index; Sulfones; Triazines; Vardenafil Dihydrochloride

Topics: Administration, Oral; Aged; Circadian Rhythm; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Erectile Dysfunction; Follow-Up Studies; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Piperazines; Prostate; Prostatectomy; Risk Assessment; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Following a report of sudden hearing loss in a patient taking phosphodiesterase type 5 inhibitor, and a Food and Drug Administration announcement concerning this class of drugs, a study was planned to investigate if ototoxicity occurs in patients using phosphodiesterase 5 inhibitor for erectile dysfunction.. Eighteen patients with erectile dysfunction who had been using phosphodiesterase 5 inhibitor were included in the study. Audiometric tests were performed on all patients, between the frequencies 250 and 16,000 Hz, before and 1, 5 and 72 hours after drug ingestion.. Four patients showed a unilateral threshold decrease compatible with ototoxicity criteria; this change was reversible. A statistically significant difference in pre- versus post-drug hearing thresholds was observed in the right ear at 10,000 Hz (p = 0.008). There were no statistically significant hearing threshold differences at any other frequencies (p > 0.05).. Although temporary ototoxicity was noted in four patients, we could not find any permanent, deleterious effect of phosphodiesterase type 5 inhibitor on hearing thresholds.

Topics: Aged; Audiometry; Dose-Response Relationship, Drug; Drug Administration Schedule; Erectile Dysfunction; Hearing Loss, Sudden; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

Phosphodiesterase type 5 (PDE5) inhibitors are widely used as first-line therapy for erectile dysfunction (ED). Their efficacy and safety combined with an increasing understanding of cyclic guanosine monophosphate (cGMP)-regulated mechanisms have triggered a number of attempts to determine their effects on the cardiovascular system and their potential benefits in cardiovascular conditions.. To review and discuss recent findings regarding the cardiovascular effects of PDE5 inhibitors and to highlight current and future clinical applications beyond ED.. Results of preclinical and clinical studies evaluating the cardiovascular effects of PDE5 inhibitors are analyzed and critically put into perspective.. Extensive PubMed literature search reviewing relevant data on effects and mechanisms of PDE5 inhibitors on the cardiovascular system.. In recent years, extensive but very heterogeneous preclinical and clinical evidence has been reported. PDE5 inhibition has proven collateral benefits for a multitude of risk factors or diseases associated with or accompanying ED. However, these agents appear to have the potential of expanding their indications. To date, PDE5 inhibition has been shown to be effective for the treatment of idiopathic pulmonary artery hypertension, and sildenafil is approved for this indication. Importantly, accumulating data show that the therapeutic potential extends to the myocardium, the coronary and peripheral arteries, subliclinical inflammation, oxidative stress, thrombosis, neurological recovery, and pathways of fibrosis. Thus, the spectrum of patients who may benefit has expanded to include, for instance, patients with heart failure or coronary artery disease.. PDE5 inhibitors are an exciting class of drugs with pleiotropic effects. Current or future PDE5 inhibitors are a conceptually attractive therapeutic strategy with potential clinical applications in a variety of cardiovascular conditions.

Topics: Erectile Dysfunction; Humans; Imidazoles; Long QT Syndrome; Male; Muscle Contraction; Myocardium; Nitric Oxide; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Risk Factors; Sulfones; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

In recent years, the availability of effective oral pharmacological treatment for erectile dysfunction (ED) has revolutionized its management; however, it is still unclear how everyday clinical practice has changed in response to this evolving scenario.. The aim of this study is to describe general practitioners' (GPs) beliefs and attitudes toward the management of ED.. Each GP was asked to recruit consecutive men aged >or=18 years and sexually active, with already known erectile problems or with newly diagnosed ED.. A written questionnaire was used to investigate GPs' sociodemographic characteristics and their beliefs toward the management of ED.. Overall, 127 GPs (53.4%) returned the questionnaire and 124 enrolled patients for the study. Only 9.5% of the GPs reported routinely inquiring about ED of patients >40 years of age, whereas 45.7% did it only when the patient raised the problem. GPs' gender and age were associated with their beliefs about ED treatment and referral to specialist care. Overall, 932 patients were enrolled, of whom 38% had newly diagnosed ED. The problem came to light for initiative of patient in 80% of cases, and 84.8% of men were prescribed a treatment. Patients who on their own initiative discussed of their condition had an almost 3-fold increased probability to be treated than those whose GP began the discussion about ED (odds ratio [OR] = 2.6, confidence interval [CI] 95% 1.5-4.5). Patients followed by female physicians were significantly more likely to be referred to a specialist than those followed by male physicians (OR = 3.3, CI 95% 1.4-5.0).. The management of ED has become an integral component of clinical practice in primary care. Nevertheless, barriers in addressing sexual issues still persist. Appropriate training is needed for a proactive approach to ED screening and management in men over 40s.

Topics: Attitude of Health Personnel; Carbolines; Cardiovascular Diseases; Drug Prescriptions; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Physician-Patient Relations; Piperazines; Practice Patterns, Physicians'; Primary Health Care; Purines; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Tadalafil; Triazines; Vardenafil Dihydrochloride

An ion mobility spectrometry (IMS) method was developed to screen for the presence of undeclared synthetic erectile dysfunction (ED) drugs or drug analogues in herbal dietary supplements claiming to enhance male sexual performance. Ion mobility spectra of authenticated reference materials including three FDA approved drugs (sildenafil citrate, tadalafil, vardenafil hydrochloride trihydrate) and five previously identified synthetic analogues (methisosildenafil, homosildenafil, piperidenafil, thiosildenafil, thiomethisosildenafil) were measured to determine their reduced ion mobilities (K(0)). All eight compounds exhibited reduced mobilities between 0.8257 and 1.2876 cm(2)/(Vs). Twenty-six herbal products were then screened for the presence of these compounds, and 15 of the 26 products tested positive for the presence of ED drug or drug analogue adulterants based on their reduced ion mobilities. IMS results were compared against the results obtained from an independent LC/MS reference method for the identical samples. Herbal dietary supplements containing adulterants were classified with 100% accuracy and most of the adulterants were correctly identified by a comparison of the K(0) of the adulterant to the K(0) of the authenticated reference material. The results demonstrate that IMS is a viable method for screening herbal dietary supplements for the presence of ED drug or drug analogue adulterants.

Topics: Adult; Amines; Carbolines; Dietary Supplements; Drug Contamination; Erectile Dysfunction; Humans; Imidazoles; Ions; Male; Piperazines; Plant Preparations; Purines; Reference Standards; Sildenafil Citrate; Spectrum Analysis; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

To assess whether the longer half-life of tadalafil is associated with longer lasting or more severe side-effects than the other phosphodiesterase type 5 inhibitors (PDE-5Is), as clinical trials have shown that the efficacy and safety of the three available are similar, but tadalafil has a half-life four times longer than the other two drugs.. Treatment-naive men beginning PDE5-I therapy were recruited from a specialist clinic. Data on the type and duration of drug-associated side-effects were collected prospectively. Levels of bother were assessed with a visual analogue scale (VAS). Differences in type, duration and bother of side-effect were compared between drugs.. In all, 409 men provided data; there were no differences between drugs in the proportion of men responding, or the overall prevalence of side-effects. The mean duration of side-effects with tadalafil was 14.9 h, compared to 3.9 and 7.7 h for sildenafil and vardenafil. Of men taking tadalafil, 30% had side-effects lasting >12 h. There were no differences in mean VAS scores between the drugs. Individual side-effects caused similar levels of bother, except for facial flushing, which was less bothersome.. Men taking tadalafil are at risk of prolonged side-effects, although levels of bother associated with these side-effects are not significantly greater than those seen with short-acting PDE5-Is.

Topics: Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Purines; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Tadalafil; Time Factors; Triazines; Vardenafil Dihydrochloride

Diabetes mellitus is associated with impaired cavernosal smooth muscle relaxation (CSMR) and the development of erectile dysfunction (ED). Vardenafil, a phosphodiesterase type 5 inhibitor has been used to treat ED. The aim of this study was to assess the in vitro and in vivo effects of vardenafil on diabetic rabbit CSMR.. Organ bath studies were used.. Sodium nitroprusside (SNP)- and electrical field stimulation (EFS)-induced CSMR in diabetic rabbits given the vehicle was significantly impaired when compared with controls. The in vitro addition of vardenafil significantly enhanced SNP-induced CSMR in diabetic animals given the vehicle. SNP-induced CSMR in diabetic animals given in vivo vardenafil was significantly increased when compared with the diabetic untreated group. The in vitro addition of vardenafil significantly enhanced SNP and EFS-induced CSMR in cavernosal tissue taken from diabetic animals given vardenafil in vivo.. The present findings suggest that the combination of in vitro and in vivo vardenafil enhance diabetic CSMR, reinforcing the use of vardenafil for the treatment of diabetes-induced ED.

Topics: Animals; Cyclic Nucleotide Phosphodiesterases, Type 5; Diabetes Mellitus, Experimental; Disease Models, Animal; Dose-Response Relationship, Drug; Electric Stimulation; Erectile Dysfunction; Imidazoles; Male; Muscle Relaxation; Muscle, Smooth; Nitroprusside; Penis; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Rabbits; Sulfones; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Topics: Drug Administration Schedule; Erectile Dysfunction; Humans; Imidazoles; Long-Term Care; Male; Middle Aged; Penile Erection; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Randomized Controlled Trials as Topic; Sulfones; Triazines; Vardenafil Dihydrochloride

This study examined 72 patients with obstructive sleep apnoea syndrome (OSAS), confirmed by polysomnography. Thirty-two patients were suffering from erectile dysfunction (ED) assessed by IIEF-5 questionnaires and confirmed by nocturnal penile tumescence examination. Their testosterone levels were measured. Eight patients had normal testosterone levels and were treated with a PDE-5 inhibitor (vardenafil) only; after 6 months of treatment, 6 of these patients (75%) showed significant improvement in erectile function. The remaining 24 patients with OSAS, ED and hypogonadism (total testosterone <12 nmol l(-1)), were divided into two groups based on the indication for continuous positive airway pressure (CPAP) therapy: five patients received CPAP therapy (group 1) and 19 patients did not (group 2). The patients of group 2 received only a PDE-5 inhibitor (vardenafil 20 mg) for ED; and eight patients (42%) showed an improvement after 3 months of treatment. The five patients receiving CPAP therapy were treated with a combination of parenteral testosterone undecanoate and a PDE-5 inhibitor (vardenafil) and all had normal erectile function after 3 months of therapy. The results suggest positive effects of addition of testosterone to treatment with PDE-5 inhibitors in hypogonadal men with OSAS, which should be confirmed in larger controlled studies.

Topics: Adult; Continuous Positive Airway Pressure; Erectile Dysfunction; Humans; Hypogonadism; Imidazoles; Male; Middle Aged; Penile Erection; Phosphodiesterase Inhibitors; Pilot Projects; Piperazines; Sleep Apnea, Obstructive; Sulfones; Testosterone; Triazines; Vardenafil Dihydrochloride

The Erectile Dysfunction Observational Study (EDOS) is a 6-months observational prospective multicentric study enrolling men with erectile dysfunction (ED) who asked, to be started on a treatment or to change a previous treatment. Aims of the study were to analyse the pattern of treatment and compare the efficacy of treatments used. Patients were enrolled during a normal hospital visit and were prescribed a treatment for ED. They were asked at baseline and after 3 and 6 months, to answer a set of questions from the International Index of Erectile Function, Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) and Short Form of the Psychological and Interpersonal Relationships Scale questionnaires (SF-PAIRS). Clinicians were free to prescribe any therapy for ED available in the market, and to change therapy at any time during the study. Out of 1 338 patients, available for analysis at 6 months, 624 (47%) changed their treatment during the study and 714 (53%) continued with the drug prescribed at baseline. Patients assuming tadalafil had a significantly higher probability of maintaining the same treatment compared to sildenafil or vardenafil. There was no clinically significant difference in terms of efficacy, patient satisfaction, self-confidence and spontaneity between the different inhibitors of PDE5. The 'time concerns' domain score of SF-PAIRS, was statistically better in patients assuming tadalafil. In conclusion sildenafil, vardenafil and tadalafil show similar efficacy in the clinical practice. However, patients receiving tadalafil display a lower risk to discontinue or change the treatment.

Topics: Adult; Aged; Aged, 80 and over; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Practice Patterns, Physicians'; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction has usually been treated by a phosphodiesterase 5 inhibitor in men, especially in the past decade. Although sildenafil and vardenafil are widely used, there is a high percentage of people who do not respond to these drugs. This study was performed in order to evaluate the efficacy of the lastly presented phosphodiesterase 5 inhibitor, tadalafil, in nonresponder group of patients to sildenafil and vardenafil.. Forty married men with erectile dysfunction who had taken sildenafil or vardenafil at the maximum recommended doses and had not responded to the treatment were included. They were treated with tadalafil, 20 mg, at least 4 doses at different days. The effectiveness of the treatment was reviewed by different questionnaires, including the International Index of Erectile Function-5 (IIEF-5), Sexual Encounter Profile (SEP) questions 2 and 3, and the Global Assessment Question (GAQ), at the end of the 12th week.. The IIEF-5 scores were 11.90 +/- 4.78 and 12.67+/-6.70, before and after at least 4 doses of tadalafil, respectively (P = .30). The rate of positive responses to SEP2, SEP3, and GAQ questions were also insignificantly different after the treatment. During this period, flushing was seen in 10 and headache was seen in 5 patients.. The recommended maximum dose for tadalafil insignificantly improved the IIEF5, SEP2, SEP3, and GAQ scores in patients with erectile dysfunction who had not responded to sildenafil and vardenafil. The other treatment alternatives should be in mind after getting no response to the optimum doses and enough trials of sildenafil or vardenafil before trying a tadalafil regimen.

Topics: Aged; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Failure; Triazines; Vardenafil Dihydrochloride

All three phosphodiesterase-5 (PDE5) inhibitors for the treatment of the erectile dysfunction have similar efficacy and toxicity profiles. Sildenafil and vardenafil have similar molecular structures, but tadalafil is structurally different, which is reflected in its pharmacokinetic profile. These pharmacokinetic differences among the PDE5 inhibitors may underlie patient preference, an important and emerging aspect of ED therapy.. The study is conducted to show and compare efficacy and safety of the three PDE-5 inhibitors and to assess patient's preference in the treatment of erectile dysfunction. It's still unknown which of the three PDE-5 inhibitors is used the most.. Study is conducted during two years on 53 patients with erectile dysfunction. Evaluation is done after 8 weeks of initial treatment followed by a 1-week washout period and then continued the therapy with the second and third medicine by the same protocol.. After three months of the treatment, patients' preference was as follows: 33 patients (62%) choose tadalafil, 13 patients (24%) choose sildenafil and 7 patients (14%) choose vardenafil. Choice of PDE-5 for initial treatment was a significant predictor for substitution from one drug to another.. Frequency of sexual intercourse (occasional use or regular therapy) and personal experience will determine the medicine of choice. When choosing medicine, attention should be paid to the beginning of its functioning, duration and possible interaction with food.

Topics: Adolescent; Adult; Aged; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Preference; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Young Adult

To explore the drug treatment for temporary ejaculation failure in couple undergoing assisted reproductive technologies (ART).. Case report.. Andrology unit, center for reproductive medicine.. Five patients suffering from temporary ejaculation failure during ART.. Assisted reproductive technology. Semen samples were collected by masturbation. The combined use of phosphodiesterase-5 inhibitor (PDE5-I; vardenafil, 10 mg) and selective serotonin reuptake inhibitor (SSRI; sertraline, 50 mg) to treat patients who failed to collect semen on the day of egg retrieval.. Five patients with unexpected ejaculation failure during ART treatments were identified; two patients could not produce spermatozoa 3 h after taking PDE5-I (sildenafil, 50 mg), However, the use of PDE5-I (vardenafil, 10 mg) plus SSRI (sertraline, 50 mg) enabled them to provide spermatozoa successfully. It suggested that the combined protocol could be more efficient for temporary ejaculation failure than sildenafil alone. On the day of the egg retrieval, we directly prescribed vardenafil and sertraline for the other three patients and got sperm samples without difficulty 2 h later.. The results indicate that the combined protocol of vardenafil plus sertraline could resolve the unpredictable ejaculation failure during ART. We presume that it might be helpful for attenuating the patients' stress and anxiety.

Topics: Adult; Ejaculation; Erectile Dysfunction; Fertilization in Vitro; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Selective Serotonin Reuptake Inhibitors; Sertraline; Sulfones; Triazines; Vardenafil Dihydrochloride

Topics: Adrenergic alpha-Antagonists; Benzhydryl Compounds; Cresols; Doxazosin; Drug Therapy, Combination; Enzyme Inhibitors; Erectile Dysfunction; Finasteride; Humans; Imidazoles; Male; Muscarinic Antagonists; Phenylpropanolamine; Piperazines; Prostatic Hyperplasia; Sulfonamides; Sulfones; Tamsulosin; Tolterodine Tartrate; Triazines; Urination Disorders; Vardenafil Dihydrochloride

The medicalisation of life problems has been occurring for well over a century and has increased over the past 30 years, with the engines of medicalisation shifting to biotechnology, managed care, and consumers. This paper examines one strand of medicalisation during the last century: direct-to-consumer advertising (DTCA) of pharmaceuticals. In particular, it examines the roles that physicians and the Food and Drug Administration (FDA) have played in regulating DTCA in the US. Two advertising exemplars, the late 19(th) century Lydia E. Pinkham's Vegetable Compound (for 'women's complaints') and contemporary Levitra (for erectile dysfunction) are used to examine the parallels between the patent medicine era and the DTCA era. DTCA re-establishes the direct and independent relationship between drug companies and consumers that existed in the late 19(th) century, encouraging self-diagnosis and requests for specific drugs. The extravagant claims of Lydia Pinkham's day are constrained by laws, but modern-day advertising is more subtle and sophisticated. DTCA has facilitated the impact of the pharmaceutical industry and consumers in becoming more important forces in medicalisation.

Topics: Advertising; Commerce; Community Participation; Drug Industry; Erectile Dysfunction; Female; History, 20th Century; History, 21st Century; Humans; Imidazoles; Male; Piperazines; Sociology, Medical; Sulfones; Triazines; Vardenafil Dihydrochloride

The objective of this study was to identify the use of phosphodiesterase type 5 inhibitors among university students from the city of Sao Paulo (SP) in Brazil. Male students (n=350) replied to a questionnaire about diagnosis of erectile dysfunction, the frequency and reason for the use of phosphodiesterase type 5 inhibitors, the specific medication used, whether their use was accompanied by a medical prescription and any reported side-effects. The results shows that a total of 53 (14.7%) students had already used this kind of medication without a prescription or medical diagnosis for erectile dysfunction, of which 53% reported using sildenafil, 37% tadalafil and 10% vardenafil. The main adverse side-effects reported were headache (23%) and flushing (10%) and the main reasons for using the inhibitor were curiosity (70%) and erectile improvement (12%).

Topics: Adolescent; Adult; Brazil; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Self Medication; Sildenafil Citrate; Students; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents; Young Adult

To observe the efficacy and safety of vardenafil in the treatment of erectile dysfunction (ED) in aged men with diabetes mellitus (DM).. One hundred outpatients with diagnosed ED (40 diabetic and 60 non-diabetic) received vardenafil at the initial dose of 20 mg and sustained dose of 10 mg once a week for 8 weeks, and their erectile functions were evaluated by IIEF and EQS.. The scores on IIEF and EQS in the diabetic ED group were 18.9 +/- 0.2 and 25.1 +/- 1.4 after the vardenafil treatment, significantly higher than 8.1 +/- 0.5 and 9.1 +/- 1.3 before the treatment (P < 0.01), and the non-diabetic group scored 21.1 +/- 0.2 and 34.2 +/- 1.2 on IIEF and EQS after the treatment, as compared with the statistically lower scores of 10.1 +/- 0.3 and 10.1 +/- 1.7 before it (P < 0.01). The total rate of effectiveness was 65% in the diabetic and 73.30% in the non-diabetic group, with statistical differences (P < 0. 05).. Vardenafil can significantly improve erectile function and is well tolerated in the aged males with diabetic ED.

Topics: Aged; Aging; Diabetes Mellitus, Type 2; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

We report our initial experience with salvage therapy for low responders to PDE-5 inhibitors by adding vitamin E. Of 89 patients with ED who visited our clinic between January 2004 to August 2006, 9 were unable to obtain a full response to a PDE-5 inhibitor and included in the present study. After providing informed consent, each was given 300 mg per day of alpha-tocophenol at least 1 month and completed IIEF-5 questionnaires to assess its efficacy while also taking a PDE-5 inhibitor. With alpha-tocophenol administration, the average IIEF-5 score increased from 13.8 +/- 3.2 to 17.1 +/- 3.6. Four of seven patients who completed the questionnaire each time showed improved IIEF-5 scores, with a maximum elevation of 9 points. Further, eight of the nine patients experienced favourable subjective changes, the majority being increased penile rigidity. The present clinical trial results are, to our knowledge, the first known to show the effects of vitamin E for enhancing the efficacy of a PDE-5 inhibitor.

Topics: Aged; Drug Therapy, Combination; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Oxidative Stress; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Purines; Salvage Therapy; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Vitamin E

Assess acceptance of and discontinuation rate from erectile dysfunction (ED) treatment in patients after bilateral nerve-sparing radical retropubic prostatectomy (BNSRRP).. We analyzed acceptance and discontinuation data of 100 consecutive, age-comparable, preoperatively self-reported potent BNSRRP patients who at the discharge from the hospital received a phosphodiesterase type 5 inhibitor (PDE5-I) prescription. Patients were informed of the pharmacokinetic properties of the available compounds and the option of on-demand versus rehabilitative therapy. Thereafter, patients did not receive any specific counseling throughout the entire follow-up period and freely decided to use or not use any ED therapy. Complete preoperative data were obtained on hospital admission and included a medical and sexual history and the International Index of Erectile Function (IIEF). The IIEF was completed every 6 mo postoperatively, and patients participated in a semi-structured interview about the treatment adherence at the 18-mo follow-up.. Forty-nine (49%) patients freely decided not to start any ED therapy (group 1). Of the remaining patients, 36 (36%) opted for an as-needed PDE5-I (group 2), whereas 15 (15%) decided to use a daily PDE5-I (group 3). At the 18-mo follow-up, the overall discontinuation rate from both treatment modalities was 72.6% (eg, 72.2% vs. 73.3% in group 2 vs. group 3; p=0.79). Treatment effect below expectations was the main reason for treatment discontinuation, followed by loss of interest in sex due to partner's causes.. Almost 50% of BNSRRP patients freely decided not to start any ED treatment postoperatively. Roughly 73% of patients who started therapy eventually discontinued it.

Topics: Carbolines; Erectile Dysfunction; Follow-Up Studies; Humans; Imidazoles; Male; Middle Aged; Patient Compliance; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Postoperative Complications; Prostate; Prostatectomy; Prostatic Neoplasms; Purines; Quality of Life; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Tadalafil; Time Factors; Treatment Outcome; Treatment Refusal; Triazines; Vardenafil Dihydrochloride

There are three phosphodiesterase type 5 (PDE5) inhibitors marketed, sildenafil, Vardenafil, and tadalafil for oral treatment of erectile dysfunction (ED). Although the treatment is simple and mostly effective, around 50% has ceased to use the medication within 2 years. One recently described way to improve the compliance is to let the patient try all the three PDE5 inhibitors and to prescribe the drug(s) he and his partner desires.. To study long-term compliance among patients who were treated according to this "three-drug regime.". Compliance and reasons for discontinuation after >2 years.. The men who, during 2003, were enrolled in a treatment regime, where they had the opportunity to test all the three drugs and to chose the one(s) they preferred, were interviewed in 2006 by telephone concerning their ongoing ED treatment and the reason for discontinuation.. Of the 138 men, mean age 60 years (36-79 years), who had been enrolled and successfully treated with the three-drug regime, 127 (92%) could be reached. The mean follow-up time was 27 months (23-34 months). Of the 127 men, as many as 109 (86%) were still using PDE5 inhibitors. A few (8%) used more than two tablets per week. The majority (44%) used one to two tablets per week or one to two per month (43%), the others (5%) less often. The causes for discontinuation were varying. The most common reason (N = 7) was return of a satisfactory non-assisted erection. Seventy-five percent of the men used only one drug; the others switched between a short- and long-acting drug depending on the situation. It was not uncommon (25%) that the preference had changed during the 3 years of PDE5 inhibitor use.. To let patients with ED test the three available PDE5 inhibitors results in an unusually high compliance even under an extended period of time (>2 years).

Topics: Adult; Aged; Carbolines; Erectile Dysfunction; Follow-Up Studies; Humans; Imidazoles; Longitudinal Studies; Male; Middle Aged; Patient Compliance; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Topics: Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Diabetic men generally have reduced efficacy with PDE-5 inhibitors (PDE5i) for the treatment of erectile dysfunction (ED).. To determine whether chronic vardenafil exposure alters cavernous protein expression predicting improved erectile function in diabetes.. 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.. Vehicle or vardenafil 0.5mg/kg/day by oral gavage for 6 wk.. Erectile function, penile tissue morphology, protein expression and surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI) protein profiling were determined.. 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.. 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.

Topics: Animals; Diabetes Mellitus, Experimental; Disease Models, Animal; Drug Administration Schedule; Endothelium; Erectile Dysfunction; Imidazoles; Male; Penile Erection; Penis; Phosphodiesterase Inhibitors; Piperazines; Protein Biosynthesis; Rats; Rats, Sprague-Dawley; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Sulfones; Triazines; Vardenafil Dihydrochloride

Topics: Drug Administration Schedule; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

To evaluate the levels of circulating progenitor cells (PCs) and the effect of a single dose of vardenafil 20mg on the number of these cells in men with erectile dysfunction (ED) and various degree of vascular injury at the carotid artery level.. Sixty-eight patients with ED and various degree of carotid damage, and 25 controls were enrolled. Patients were divided into three groups according to their intima media thickness (IMT) status (normal, mild increase, or plaque). All subjects received vardenafil 20mg, and evaluation of the number of circulating PCs was performed at baseline and 4h after vardenafil administration. An RNA expression analysis of phosphodiesterase type 5 (PDE5) on bone marrow was also performed.. We found a significant reduction of circulating PCs in ED patients with respect to controls and a reduction in PC counts in patients with mild IMT increase or plaque, but not in those with normal IMT. Four hours after vardenafil administration we observed an increase in the number of PCs in all patients and controls. Reverse transcriptase-polymerase chain reaction analysis showed that human bone marrow expresses PDE5 messenger RNA.. Patients with ED and a low number of circulating PCs may be considered at increased risk for an endothelial dysfunction. An impaired response to vardenafil stimulus may be proposed as a surrogate marker of a patient's endothelial regenerative ability.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Blood Cell Count; Bone Marrow Cells; Carotid Artery Diseases; Cyclic Nucleotide Phosphodiesterases, Type 5; Endothelial Cells; Endothelium, Vascular; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Stem Cells; Sulfones; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Nitrergic neurons are important for erectile responses in the corpus cavernosum and impaired signalling results in erectile dysfunction, today treated successfully by oral administration of the selective phosphodiesterase 5 (PDE 5) inhibitors sildenafil, tadalafil and vardenafil. Although the importance of nitrergic neurons in urogenital function has become evident, it has not been investigated if the PDE 5 inhibitors affect the nerve-induced release of nitric oxide (NO). In a previous study we found that the soluble guanylate cyclase (sGC)/cyclic guanosine 3',5'-monophosphate (cGMP) pathway might modulate nerve-induced release of NO in isolated cavernous tissue.. Electrical field stimulation (EFS 5 Hz, 40 V, 0.3 ms pulse duration, 25 pulses at intervals of 2 min) of rabbit isolated cavernous tissue elicited reproducible, nerve-mediated relaxations in the presence of scopolamine (10(-5) M), guanethidine (10(-5) M) and phenylephrine (3 x 10(-6) M). In superfusion experiments, nerve stimulation (20 Hz, 40 V, 1 ms) of the cavernous tissue evoked release of NO/NO2-, measured by chemiluminescence.. Sildenafil, tadalafil and vardenafil decreased the muscular tone and prolonged the relaxations to nerve stimulation. The evoked release of NO decreased to 72+/-11%, 55+/-16% and 61+/-14% of control, respectively after addition of sildenafil, tadalafil or vardenafil (all 10(-4) M, n=6-8, p<0.05).. Selective PDE 5 inhibitors influence the nerve-induced release of NO, probably via cGMP-mediated negative feedback. This negative feedback might explain why priapism is not seen during monotherapy with the PDE inhibitors.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Carbolines; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Imidazoles; In Vitro Techniques; Male; Muscle, Smooth; Nitrergic Neurons; Nitric Oxide; Penis; Phosphodiesterase Inhibitors; Piperazines; Priapism; Purines; Rabbits; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

The ability of oral phosphodiesterase type 5 (PDE5) inhibitor therapy to restore erectile function to normal is an important attribute to men with erectile dysfunction (ED).. To assess the ability of vardenafil to restore normal erectile function in men with general ED.. In two fixed-dose, parallel-group, double-blind, placebo-controlled, pivotal studies, patients received vardenafil (5, 10, or 20 mg) or placebo for 12/26 weeks.. In this retrospective analysis, the percentage of patients "returning to normal" erectile function at week 12 (as defined by scores > or =26 on erectile function domain of International Index of Erectile Function [IIEF-EF]) was determined, with further stratification by baseline ED severity, etiology, age, and duration of ED.. Vardenafil 5, 10, and 20 mg returned 32%, 43%, and 49% of patients, respectively, to normal erectile function after 12 weeks, compared with 10% of patients receiving placebo (P < 0.0001). Return to normal IIEF-EF domain scores was noted irrespective of severity, etiology, age, and duration of ED, and was observed even in challenging-to-treat subgroups. With vardenafil 20 mg, 39% of men with severe ED at baseline, 45-49% of men with ED of mixed or organic etiology, 35% of men aged > or =65 years, and 43% of men with ED of > or =3 years of duration returned to normal erectile function at week 12. Mean per-patient SEP3 (question 3 on the Sexual Encounter Profile) success rates in patients achieving IIEF-EF domain scores > or =26 ranged from 87% to 95%.. Vardenafil improves the IIEF-EF domain score to the normal range in a substantial proportion of men with ED.

Topics: Aged; Coitus; Dose-Response Relationship, Drug; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Randomized Controlled Trials as Topic; Reference Values; Retrospective Studies; Severity of Illness Index; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

During the past 18 years, sildenafil has evolved from a potential anti-angina drug to an on-demand treatment for erectile dysfunction and more recently to a new orally active treatment for pulmonary hypertension. Recent studies suggest that the drug has powerful cardioprotective effect against ischemia/reperfusion injury, doxorubicin-induced cardiomyopathy and anti-hypertensive effect induced by chronic inhibition of nitric oxide synthase in animals. Based on several recent basic and clinical studies, it is clear that sildenafil and other clinically approved type-5 phosphodiesterase-5 inhibitors including vardenafil and tadalafil will eventually be developed for several cardiovascular indications including essential hypertension, endothelial dysfunction, ischemia/reperfusion injury, myocardial infarction, ventricular remodeling and heart failure.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Antihypertensive Agents; Carbolines; Cardiomyopathies; Cardiovascular Agents; Cyclic Nucleotide Phosphodiesterases, Type 5; Disease Models, Animal; Doxorubicin; Endothelium, Vascular; Enzyme Inhibitors; Erectile Dysfunction; Heart Failure; Humans; Hypertension; Hypertension, Pulmonary; Imidazoles; Male; Myocardial Infarction; Myocardial Reperfusion Injury; NG-Nitroarginine Methyl Ester; Nitric Oxide; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents; Ventricular Remodeling

Clinical practice guidelines for management of erectile dysfunction (ED) provide limited direction in defining appropriate treatment goals with phosphodiesterase type 5 (PDE5) inhibitor therapy.. To establish an evidence-based position on treatment goals in ED, including the role of erection hardness, with the potential to improve self-esteem, confidence, and overall sexual and relationship satisfaction.. The target of ED therapy is optimization of a rigid erectile response, as assessed by the 4-point Erection Hardness Score (EHS). Methods. An international panel of experts in urology, psychology, and primary care convened to evaluate retrospective data from worldwide phase 2, 3, and 4 clinical trials, involving over 10,000 men with ED, as well as data from recent prospective studies, concerning the role of erection hardness in defining the response to treatment with PDE5 therapy.. Significant positive correlations were found between EHS and the Quality of Erection Questionnaire and the International Index of Erectile Function (IIEF) erectile function domain score and other IIEF measures. Significant positive correlations were also found between erection hardness and psychosocial measures such as self-esteem, confidence, and relationship satisfaction (assessed by the Self-Esteem And Relationship questionnaire), and satisfaction with medical treatment (assessed by the Erectile Dysfunction Inventory of Treatment Satisfaction). A shift in most frequent erection from EHS 3 (hard enough for penetration but not fully hard) at baseline to EHS 4 (completely hard and fully rigid) at the end of treatment was accompanied by significant improvements in intercourse and relationship satisfaction, psychosocial benefits, and satisfaction with ED treatment.. Support is found for monitoring and treating patients with ED to their full erectile potential. Quantitative assessment of erection hardness in clinical practice will lead to improved outcomes in overall sexual experience and optimal treatment satisfaction.

Topics: Adult; Coitus; Erectile Dysfunction; Evidence-Based Medicine; Humans; Imidazoles; International Cooperation; Male; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Professional-Patient Relations; Quality of Life; Sex Education; Sulfones; Triazines; United Kingdom; Vardenafil Dihydrochloride; Vasodilator Agents

To evaluate predictors of changing the type of phosphodiesterase type 5 (PDE5) inhibitor (switching) among men with erectile dysfunction (ED) in the UK, the largest consumer of PDE5 inhibitors in Europe, as switching medication is often associated with higher resource use, and there are three oral PDE5 inhibitor medications currently available.. Patients were identified from The Health Improvement Network database in the UK; men initiating therapy with sildenafil, tadalafil or vardenafil from May 2003 to August 2004 with >/= 6 months of prescription history before and after their initial PDE5 inhibitor prescription were included. Switching was evaluated as the proportion of second PDE5 inhibitor prescriptions that were for a drug differing from the first. Logistic regression was used to adjust for factors that might be associated with switching (dose, age and the presence of hypertension, dyslipidaemia, diabetes or depression).. Of the 2703 eligible men who initiated PDE5 inhibitor treatment during the study period, 91 (3.4%) switched to a different PDE5 inhibitor at their second prescription. The choice of initial PDE5 inhibitor therapy was a highly significant predictor of switching; men initiated on sildenafil were less likely to switch than those initiated on tadalafil (P < 0.001) or vardenafil (P < 0.003). Age and the presence of comorbidities were not significantly associated with switching (P > 0.05).. Initiating ED therapy with sildenafil was associated with the lowest rate of PDE5 inhibitor switching, which might reflect treatment satisfaction and patient preference.

Topics: Adolescent; Adult; Aged; Carbolines; Cohort Studies; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Purines; Retrospective Studies; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To assess the safety, efficacy and patient acceptability of vardenafil treatment under real-life conditions in patients with erectile dysfunction (ED).. The present publication shows the results of a subgroup analysis of a multinational post-marketing surveillance study, including 2824 Middle East patients with ED whose attending physician chose vardenafil as the most appropriate therapy. Patients were assessed at an initial visit for demographic and baseline characteristics. At one or two follow-up visits, covering a period of approximately 2 months or eight vardenafil intakes, patients were interviewed about overall treatment success (general improvement of erection, number of tablets taken until improvement, patient's satisfaction with overall efficacy and tolerability, comparison with last ED treatment). All adverse events were recorded and assessed for a possible relationship to treatment, and for severity.. An overall improvement in erections was reported in 94.3% of patients. Most patients achieved treatment success after the first (67.0%) or second (83.6% cumulative) tablet. Diabetic patients had a similar improvement rate (92.2%) and 73.5% of patients who had undergone radical prostatectomy reported an overall improvement. The rate of adverse drug reactions (ADRs) was low (9.1% of patients). The most common ADRs were headache (5.8%), flushing (1.6%), nasal congestion (1.0%), dyspepsia (0.6%) and nausea (0.5%). In total, 88.9% of patients wanted to continue treatment with vardenafil.. Vardenafil was effective, reliable and well tolerated in patients with ED treated under real-life conditions.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Aged; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Middle East; Phosphodiesterase Inhibitors; Piperazines; Product Surveillance, Postmarketing; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Pharmaceutical counterfeiting and purchasing medicines from illegal distribution channels have become more and more common problem in our country. Different medicines, especially erectile dysfunction drugs are involved. The aim of this study was the qualitative analysis of fake Levitra tablets and the estimation of the risk they bear to potential users. Tablets were secured by the police and delivered to Bayer office in 2006.. Trace amount of sildenafil (the active ingredient of Viagra) and not vardenafil (the active ingredient of Levitra) was found in tablets described as "Levitra" (vardenafil). The presence of this substance was discovered by NIR--and Raman spectroscopy. The appearance of tablets and blisters corresponded to the original product. There were no paper boxes and patient information leaflets attached. As prescription medicines erectile dysfunction drugs should be purchased from a pharmacy only. They need to be used under strict medical control.

Topics: Carbolines; Drug Compounding; Drug Contamination; Drug Industry; Drug Labeling; Drug Packaging; Erectile Dysfunction; Fraud; Humans; Imidazoles; Legislation, Drug; Male; Phosphodiesterase Inhibitors; Piperazines; Poland; Public Health; Purines; Quality Control; Risk Assessment; Sildenafil Citrate; Spectrum Analysis, Raman; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

This report describes patterns of treatment changes with the phosphodiesterase type 5 (PDE5) inhibitors tadalafil, sildenafil and vardenafil, and variables associated with those treatment changes, during the 6-month, prospective, pan-European Erectile Dysfunction Observational Study (EDOS).. EDOS observed 8047 men > or = 18 years old with erectile dysfunction (ED), who began or changed ED therapy as part of their routine healthcare. Patients could change ED treatment at any time during EDOS. Data were collected at baseline and at 3 (+/- 1) and 6 (+/- 1) months. Analyses included ED treatment-naïve patients with complete follow-up who were prescribed a PDE5 inhibitor at baseline (n = 4026).. Most patients, regardless of what PDE5 inhibitor they were prescribed at baseline, continued on that same PDE5 inhibitor throughout the study. Continuation rates were approximately 89% in the tadalafil cohort, vs. 63-64% in the sildenafil and vardenafil cohorts. The variables most strongly associated with increased risk of switching were prescription of sildenafil or vardenafil, vs. tadalafil, at baseline (odds ratios 4.43 and 4.14 respectively; p < 0.0001). Of patients who switched from tadalafil to another treatment, nearly 25% had switched back to tadalafil by study end. In contrast, of patients who switched from sildenafil or vardenafil, < 10% from each cohort had switched back to their original treatment by study end.. The data suggest that tadalafil treatment in treatment-naïve ED patients may increase their likelihood of treatment continuation. These findings should be interpreted conservatively due to the observational nature of the study.

Topics: Adolescent; Adult; Aged; Carbolines; Cohort Studies; Erectile Dysfunction; Follow-Up Studies; Humans; Imidazoles; Male; Middle Aged; Patient Compliance; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Purines; Regression Analysis; Severity of Illness Index; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Tadalafil; Time Factors; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To investigate the problem of drug analogue adulteration in male erectile dysfunction health products.. Survey of over-the-counter male erectile dysfunction health products available in convenience stores and pharmacies in Hong Kong.. Tertiary referral centre for clinical toxicology analysis in Hong Kong.. The pattern and extent of adulteration of male erectile dysfunction health products with sildenafil, tadalafil, and vardenafil as well as their structurally modified analogues.. Of 26 products studied, one (4%) was found to contain undeclared sildenafil, while 14 (54%) contained drug analogues of different kinds. The latter included acetildenafil, hydroxyacetildenafil, hydroxyhomosildenafil, and piperidenafil. The first three were analogues of sildenafil and the last was an analogue of vardenafil. One young patient presented with ataxia after taking an acetildenafil-containing product.. The positive rate of concealed drug analogues in male erectile dysfunction health products is alarmingly high. Such analogues are difficult to detect by ordinary laboratory methods, and might be used in an attempt to evade regulatory inspection. Without going through the stringent drug testing process, the adverse effects of these chemicals remain largely unknown and unpredictable. Effective surveillance system and control measures are needed urgently. The medical profession and the public should be alerted to this under-recognised threat.

Topics: Adult; Ataxia; Carbolines; Data Collection; Drug Contamination; Erectile Dysfunction; Hong Kong; Humans; Imidazoles; Male; Nonprescription Drugs; Phosphodiesterase Inhibitors; Piperazines; Plant Preparations; Purines; Pyrimidinones; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Topics: Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Nursing Assessment; Patient Education as Topic; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Topics: Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Optic Neuropathy, Ischemic; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Topics: Aged; Cerebral Hemorrhage; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride; Vision Disorders; Visual Fields

Topics: Carbolines; Contraindications; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Testosterone; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adverse Drug Reaction Reporting Systems; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Optic Neuropathy, Ischemic; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vision Disorders

In clinical practice, to apply and evaluate outcomes of a treatment regime, in which the patient had the opportunity to try all the available phosphodiesterase 5 (PDE5) inhibitors.. Patients eligible for treatment with PDE5 inhibitors were prescribed 8 tablets with a shorter-acting substance (four tablets sildenafil 100mg and four tablets vardenafil 20mg) and eight tablets with a long-acting substance (tadalafil 20mg). Outcomes of the regime were recorded.. Of the 186 patients, 64 (34%) had not been treated previously (naïve), and 122 (66%) were undergoing treatment for their erectile dysfunction. The overall treatment response was 89% (165 of 186 patients); 78% (n=145 of 186 patients) tested all three substances. No significant difference in choice between long- and shorter-acting medications in the overall material was observed. Two thirds of the naïve patients (n=64) preferred a shorter-acting substance (p<0.01). Every fifth man requested both a shorter- and a long-acting medication to accommodate his need.. If patients are given the opportunity in clinical practice to try all three available PDE5 inhibitors, the overall response rate is very high, almost 90%. No significant difference in patient preference between long- and shorter-acting drugs was observed. Treatment choice was based mainly on efficacy or duration of effect.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Administration, Oral; Adult; Aged; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Prescriptions; Drug Therapy, Combination; Erectile Dysfunction; Feasibility Studies; Follow-Up Studies; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Retrospective Studies; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To develop and test step-wise treatment strategy for erectile dysfunction "non-responders" to tadalafil and vardenafil.. Two groups [tadalafil-treated (TG); vardenafil-treated (VG)] of 100 consecutive patients complaining of non-response to treatments were enrolled in three-phase study. Phase 1: inadequate use was identified and patients were rechallenged, after receiving detailed usage information. Phase 2: true non-responders were given new instructions based on drugs' pharmacologic profiles: TGs were dosed at least 2 h before intercourse; VGs were dosed only in fasted state. Remaining non-responders entered phase 3: continuous administration of 20 mg tadalafil every other day, or 20 mg vardenafil every day for 2 weeks. Efficacy was based on positive (yes) response to two questions: "Were your erections rigid, and did they last long enough to have successful intercourse?" and "Do you want to repeat your prescription?". Tadalafil group: Inappropriate use was recognized in 32 patients; 14 (43.75%) responded after adequate instruction. Phase 2: 32 of 86 (37.2%) had intercourse at least 2 h after dose intake. Phase 3: 6 of 86 (11.1%) responded to continuous administration. Overall salvage rate was 52 of 100 (52%). Vardenafil group: Inappropriate use was recognized in 38 patients; 12 (31.58%) responded after adequate instruction. Phase 2, 22 of 88 (25%) responded to dosing in a fasted state. Phase 3: 12 of 66 (18.2%) responded to daily dosing. Overall salvage rate was 46 of 100 (46%).. Following proposed treatment strategy may maximize response rate to phosphodiesterase 5 inhibitors; appropriate usage instructions may play significant role in response rate.

Topics: Adult; Aged; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

This paper reviewed the efficacy and safety of vardenafil, a highly selective phosphodiesterase type 5 (PDE 5) inhibitor, in men with erectile dysfunction who were difficult to treat. Several large-scale studies indicated vardenafil was effective and safe in the treatment of these difficult-to-treat ED patients, including ED with depression or diabetes, ED after radical retropubic prostatectomy, ED caused by spinal cord injury, and sildenafil nonresponders. Vardenafil provides a rational treatment alternative.

Topics: Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Epileptic seizures complicating treatment with selective inhibitors of phosphodiesterase type 5 are scarcely reported.. A previously non-epileptic 78-year-old patient presented with a partial epileptic seizure following oral intake, for the second time, of 10mg of vardenafil (Levitra). The brain MRI failed to show any preexisting lesion. To our knowledge, only 2 cases of generalized tonic-clonic seizures induced by sildenafil (Viagra) use have been reported. In our patient, the seizure could be due to the epileptogenic potential of the drug or to its vascular complications.. Further studies are needed to elucidate the association of phosphodiesterase inhibitors use and epileptic seizures.

Topics: Aged; Brain; Carbamazepine; Electroencephalography; Epilepsy, Tonic-Clonic; Erectile Dysfunction; Frontal Lobe; Humans; Image Enhancement; Imidazoles; Magnetic Resonance Imaging; Male; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Tomography, X-Ray Computed; Triazines; Vardenafil Dihydrochloride

The role of female partners in the diagnosis and treatment of erectile dysfunction (ED) is being paid more and more attention now. ED has serious adverse effects on the sexual experience of female partners, while the attitudes of female partners to ED will have a direct effect on seeking and continuing treatment behavior of ED patients. So it's necessary for clinicians to consider female partners in the clinical practice of ED. The evidence from a recently published clinical trial has demonstrated that vardenafil not only improved ED men's erectile function, but also improved the sexual quality of life for female partners, which was the ideal solution of ED couples.

Topics: Erectile Dysfunction; Female; Humans; Imidazoles; Male; Piperazines; Sexual Partners; Sulfones; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Atherosclerosis; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Optic Neuropathy, Ischemic; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vision Disorders

Topics: Comorbidity; Depressive Disorder, Major; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Paraphilic Disorders; Phosphodiesterase Inhibitors; Piperazines; Severity of Illness Index; Substance-Related Disorders; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Reliable efficacy is very important to continuing treatment for patients with erectile dysfunction. Vardenafil is a potent, highly selective phosphodiesterase 5 (PDE5) inhibitor. The efficacy and safety of vardenafil has been confirmed in many clinical studies. This paper analyzed the efficacy reliability of vardenafil in clinical trials and real-life practice, concluded that it provided reliable efficacy for key parameters of erection and improved treatment compliance.

Topics: Adult; Aged; Clinical Trials, Phase III as Topic; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Randomized Controlled Trials as Topic; Retrospective Studies; Sulfones; Triazines; Vardenafil Dihydrochloride

Topics: Adult; Aged; Coitus; Erectile Dysfunction; Half-Life; Humans; Imidazoles; Male; Middle Aged; Piperazines; Sulfones; Time Factors; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Topics: Administration, Oral; Epilepsy; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

The prevalence of erectile dysfunction (ED) is higher in hypertension patients than in non-hypertension men. Because doctors worry about the severe adverse events of drug combination, they tend to be reluctant to prescribe ED medicines for patients. Vardenafil, as a novel and highly selective phosphodiesterase 5 inhibitor, has been proved by many clinical trials to be quite safe for the cardiovascular system. A recent large-scale clinical trial showed that vardenafil could improve erectile function in ED men with hypertension, with sure safety and no significant clinical changes in the index of hypertension or heart rate.

Topics: Adult; Aged; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Topics: Carbolines; Contraindications; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Topics: Adult; Aged; Carbolines; Clinical Trials as Topic; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Topics: Carbolines; Contraindications; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphoric Diester Hydrolases; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Topics: Carbolines; Erectile Dysfunction; Formularies as Topic; Humans; Imidazoles; Insurance Coverage; Insurance, Pharmaceutical Services; Male; Managed Care Programs; Medicare; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; United States; Vardenafil Dihydrochloride

Topics: Adult; Age Factors; Aged; Carbolines; Contraindications; Drug Interactions; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones; Tadalafil; Time Factors; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

The remarkable therapeutic success of PDE5 inhibitors in the treatment of male erectile dysfunction has focused the attention of the researchers on better defining the properties of the individual inhibitors and PDE5 that contribute to the high affinity of these inhibitors for interaction with the PDE5 catalytic site. Recent molecular studies have demonstrated that vardenafil has high affinity for PDE5 and low dissociation rate from PDE5, which serves to explain why vardenafil works with low dosage, onsets quickly and has curative action in clinical practice. Moreover, the potency of vardenafil depends on its ring structure that resembles the purine moiety in cGMP.

Topics: Drug Interactions; Erectile Dysfunction; Humans; Imidazoles; Male; Molecular Structure; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

Topics: Adult; Aged; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Multicenter Studies as Topic; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Surveys and Questionnaires; Time Factors; Triazines; Vardenafil Dihydrochloride

Topics: Clinical Competence; Erectile Dysfunction; Humans; Imidazoles; Male; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Safety; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To investigate the effects of hypercholesterolaemia (HC) on rabbit corpus cavernosa in vivo and in vitro, and evaluate the efficacy of vardenafil and sildenafil in normal and HC rabbits, as the phosphodiesterase-5 (PDE-5) inhibitors vardenafil and sildenafil are widely used for treating erectile dysfunction (ED) and most organic causes of ED are associated with vascular risk factors like HC.. Male New Zealand White rabbits were randomly divided into two groups; 11 HC rabbits were fed a 2% cholesterol diet, and 12 age-matched control rabbits received a regular diet. After 12-14 weeks, erectile responses to intravenous sodium nitroprusside (SNP) and PDE-5 inhibitors were evaluated for 2 h in conscious rabbits. Penile length was measured and the area under the curve calculated. Relaxant responses of corpus cavernosal strips to electrical-field stimulation (EFS) were measured before and after exposure to PDE-5 inhibitors and the nitric oxide synthase inhibitor N'-nitro-L-arginine methyl ester.. HC rabbits had a lower erectile response to SNP than controls; in both control and HC rabbits there was a greater erectile response after simultaneous exposure to SNP and vardenafil, or SNP and sildenafil. However, the responses of the HC rabbits were still significantly less than those of the controls. Corpora from control rabbits responded to EFS with greater relaxations at all frequencies, except 1 Hz. Corpora from both HC and control rabbits had greater responses to EFS after exposure to vardenafil and sildenafil; N'-nitro-L-arginine methyl ester diminished the response to EFS.. There was a significantly lower in vivo and in vitro erectile response in HC rabbits than in controls; erectile function measured in conscious rabbits can be used to assess quantitatively the efficacy of different agents, e.g. sildenafil and vardenafil, in pathological animals. In addition, both agents improve in vitro responses of erectile tissue from HC rabbits to EFS.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Area Under Curve; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Hypercholesterolemia; Imidazoles; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth; Penile Erection; Penis; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Rabbits; Sildenafil Citrate; Sulfones; Triazines; Vardenafil Dihydrochloride

There is a close relationship between sexual activity and meals or alcohol consumption. It is of great clinical significance for clinicians to understand the effects of food and alcohol on the pharmacokinetics of phosphodiesterase-5 inhibitor vardenafil so as to give correct instructions to patients. Although a high-fat ( > 55% fat calories) meal modestly reduces C(max) by 18% and prolongs t(max) of vardenafil by approximately 1 hour, no significant effects of a typical moderate-fat meal (30% fat calories) on vardenafil pharmacokinetics were observed in a study carried out in 25 healthy adult males. So the adjustment of vardenafil dosage is not warranted based on a wide therapeutic index and the efficacy observed with vardenafil in Phase III studies, which need not be restricted with respect to food. In another study, the pharmacokinetics and safety profile of vardenafil were not affected if it was taken together with 0.5 g/kg ethanol. The above characteristics of vardenafil make the administration more convenient for patients.

Topics: Adult; Alcohol Drinking; Erectile Dysfunction; Food-Drug Interactions; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

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.. 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.. 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.. 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.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Chromatography, High Pressure Liquid; Drug Contamination; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phytotherapy; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

To evaluate erectile dysfunction, penile color Doppler ultrasound is currently considered the best method. But intracavernous injection is invasive and has adverse effects, such as prolonged erection and risk of priapism. In our study we want to evaluate whether vardenafil can be used instead of papaverine in penile Doppler ultrasonography.. A total of 24 patients with erectile dysfunction underwent color Doppler ultrasound before and after intracavernous injection of 60 mg papaverine with genital and audiovisual sexual stimulation. Peak flow and end diastolic velocity were measured in the recorded waveforms obtained 0, 1, 5, 10 and 20 min after injection. The patients also underwent color Doppler ultrasound after a 10-mg oral dose of vardenafil with genital and audiovisual sexual stimulation and at least 5 days after the prior examination. The same parameters were measured at 30, 45, 60, 75 and 90 min after the drug administration. We compared the results with the values obtained after papaverine injection.. After oral vardenafil mean peak flow velocity significantly increased starting at 30 min and achieving a maximum value at 60 min. There were no significant differences in the 2 methods in mean peak velocity 1, 5, 10 and 20 min after papaverine injection, and 30, 45, 60, 75 and 90 min after oral vardenafil administration. Although papaverine injection is the gold standard for penile color Doppler ultrasound, it has severe adverse effects such as prolonged erection which we observed in 3 patients (12.5%) and required pharmacological detumescence. After vardenafil no severe adverse effects were observed.. Vardenafil administration achieved increased peak flow velocity comparable to that after intracavernous papaverine injection. With no prolonged erection vardenafil is a safer alternative compared to more invasive intracavernous injection and is also an alternative for patients who fear injections.

Topics: Adult; Arteries; Blood Flow Velocity; Drug Administration Routes; Erectile Dysfunction; Follow-Up Studies; Humans; Imidazoles; Male; Middle Aged; Papaverine; Penile Erection; Penis; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Triazines; Ultrasonography, Doppler, Color; Vardenafil Dihydrochloride

Topics: Brachytherapy; Erectile Dysfunction; Humans; Imidazoles; Male; Patient Education as Topic; Phosphodiesterase Inhibitors; Piperazines; Prostatectomy; Prostatic Neoplasms; Sulfones; Triazines; Vardenafil Dihydrochloride

Since fixed-dose vardenafil clinical trails don't fully represent utilization of phosphodiesterase-5 (PDES) inhibitor in general clinical practice. This article reviews flexible-dose and community practice studies, to assess the efficacy and safety of vardenafil in general clinical practice. The results show that vardenafil improves erectile function in most men treated for ED in clinical practice, and well tolerated.

Topics: Adult; Aged; Community Pharmacy Services; Erectile Dysfunction; Europe; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Sulfones; Triazines; Vardenafil Dihydrochloride

The Treatment Satisfaction Scale (TSS) has been developed to assess various concepts related to erectile dysfunction (ED) treatment satisfaction in patients and their partners. The self-report questionnaire consists of 4 modules: unmedicated patient, medicated patient, unmedicated partner, and medicated partner modules, measuring a range of sexuality concepts considered important by ED patients and their partners including six domains: "Confidence", "Ease with Erection", "Erectile Function Satisfaction", "Pleasure from Sexual Activity", "Satisfaction with Orgasms", and "Satisfaction with Medication". The TSS is an internationally valid, psychometrically sound instrument to assess patient and partner satisfaction with ED therapy. In a recent double-blind, multicenter, parallel arms, flexible dose clinical trial, the TSS was used to compare patient and partner's satisfaction with vardenafil and placebo therapy. The results demonstrated that vardenafil significantly improved not only erectile function, but also confidence, ease of erection, pleasure, and satisfaction with erectile function, orgasm and medication in men ED and their partners. These attributes are considered to be essential in the acceptance and continued use of PDE5 inhibitor therapy for ED.

Topics: Double-Blind Method; Erectile Dysfunction; Female; Humans; Imidazoles; Male; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Sexual Partners; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Vardenafil is a new oral phosphodiesterase inhibitor used for erectile dysfunction. We report a case admitted with a first-detected, symptomatic paroxysmal atrial fibrillation in a healthy patient after self-medication with vardenafil.

Topics: Atrial Fibrillation; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

The efficacy and tolerability of vardenafil hydrochloride in men with erectile dysfunction (ED) and a history of nonresponse to sildenafil citrate have previously been reported.. The aim of this descriptive analysis was to assess the efficacy and tolerability of vardenafil at various times after dosing in men with ED and a history of nonresponse to sildenafil and who chose to attempt sexual intercourse between 0.25 and 6 hours after dosing with vardenafil.. This analysis used data from a previously published 12-week, prospective, randomized, double-blind, flexible-dose, placebo-controlled study conducted at 41 hospitals and outpatient clinics across Australia, Europe, Asia, and North America. In that study, men with ED and sildenafil nonresponse, defined using 6 rigorous criteria (including nonresponse to the highest recommended dose, 100 mg/d) were assigned to receive vardenafil 10 mg or placebo QD. At study weeks 4 and 8, patients in both groups were given the option to maintain the 10-mg/d dose, or have the dose titrated to 5 or 20 mg/d. The present analysis used data from patient diaries completed daily, which included information concerning attempts at sexual intercourse, time from dosing to attempt, penetration, and maintenance of erection sufficient for successful intercourse. At week 12, diary data were categorized into time intervals (in hours) after dosing. For each interval, the per-patient success rate was based on the total number of attempts made in that interval. Comparative statistics were not performed on the time-interval analysis. Tolerability was monitored throughout the study. Data concerning the primary end point were reported previously.. A total of 463 men were enrolled, of whom 457 were included in the safety analysis (vardenafil, n = 231; placebo, n = 226) and 454 in the intent-to-treat analysis (vardenafil, n = 229; placebo, n = 225; mean age, 60.1 vs 59.0 years; mean body mass index, 28.7 vs 28.0 kg/m2). Six patients were excluded from the safety analysis (2 patients did not use study medication [placebo group], postbaseline safety data unavailable in 4 patients [2 in each study group]). Men receiving vardenafil had numerically greater penetration and completion success rates compared with those receiving placebo at all time intervals. Penetration success rates were numerically higher with vardenafil compared with placebo as early as within 0.25 hour after dosing (62% vs 30%); efficacy continued beyond 6 hours after dosing in 77% and 50% of patients, respectively. Similarly, vardenafil-treated patients had numerically greater completion success rates compared with those receiving placebo at 0.25 hour (53% vs 12%) and beyond 6 hours after dosing (70% vs 24%). The most common drug-related adverse events in the vardenafil and placebo groups were flushing (7% vs 1%), headache (6% vs 2%), and nasal congestion (5% vs <1%).. This descriptive analysis suggests that erection sufficient for penetration and intercourse completion was achieved within 0.25 hour and lasted for >6 hours after dosing with vardenafil 10 mg in these men with mostly moderate to severe ED and a history of nonresponse to sildenafil and who chose to make attempts during those intervals. The drug was generally well tolerated.

Topics: Adult; Aged; Aged, 80 and over; Double-Blind Method; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Multicenter Studies as Topic; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Time Factors; Triazines; Vardenafil Dihydrochloride

Topics: Clinical Trials as Topic; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Topics: Advertising; Drug Industry; Erectile Dysfunction; Humans; Imidazoles; Male; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

A number of preference studies have been conducted with phosphodiesterase type 5 (PDE5) inhibitor medications demonstrating inconsistent findings. Additionally, limited information is available regarding real-world utilization patterns of PDE5 inhibitors.. To evaluate treatment patterns using real-world data for patients initiating erectile dysfunction (ED) therapy with Viagra (sildenafil citrate), Levitra (vardenafil), or Cialis (tadalafil).. Patients with an initial prescription claim for sildenafil, vardenafil, or tadalafil were identified in NDCHealth's Intelligent Health Repository. Medication refills, medication switching, and dose titration were analyzed. Logistic regression on the odds of refilling initial PDE5 medications was conducted controlling for patient age, presence of common comorbidities, initial number of tablets, and copay.. A higher percentage of patients receiving sildenafil (52%) refilled their ED medication during the study period than patients receiving vardenafil (30%) or tadalafil (29%) (P<0.001). A smaller percentage of patients in the sildenafil cohort (6.4%) switched medication than in the tadalafil (9.0%) or vardenafil (10.4%) cohorts (P<0.001); the difference between the tadalafil and vardenafil cohorts in switching medications was also significant (P<0.001). There were no statistically significant differences between cohorts in dose titration frequency, which was low in all three treatment cohorts. Using logistic regression, the odds of refilling initial PDE5 therapy was significantly lower for vardenafil (odds ratio [OR]: 0.39, 95% confidence interval [CI]: 0.38-0.40; P<0.0001) and tadalafil (OR: 0.38, 95% CI: 0.37-0.40; P<0.0001) compared with sildenafil.. Patients who were initially prescribed sildenafil were significantly more likely to refill their medication and significantly less likely to switch medications during the study period compared with patients who were initially prescribed vardenafil or tadalafil. These findings may indicate greater treatment satisfaction in patients receiving sildenafil, although future prospective evaluation is required.

Topics: Adult; Carbolines; Drug Prescriptions; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Patient Acceptance of Health Care; Phosphodiesterase Inhibitors; Piperazines; Purines; Self Administration; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Topics: Blindness; Carbolines; Drug Prescriptions; Drug-Related Side Effects and Adverse Reactions; Erectile Dysfunction; Humans; Imidazoles; Incidence; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Assessment; Risk Factors; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; United States; Vardenafil Dihydrochloride; Vasodilator Agents; Video Recording

Topics: Carbolines; Ejaculation; Erectile Dysfunction; Humans; Imidazoles; Male; Nitric Oxide; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Topics: Carbolines; Drug Interactions; Erectile Dysfunction; Humans; Imidazoles; Male; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Topics: Carbolines; Commerce; Drug Industry; Erectile Dysfunction; Humans; Imidazoles; Male; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; United States; Vardenafil Dihydrochloride

Topics: Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Topics: Carbolines; Drug Interactions; Erectile Dysfunction; Food-Drug Interactions; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Approval; Erectile Dysfunction; Forecasting; Humans; Imidazoles; Legislation, Drug; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Enzyme Inhibitors; Erectile Dysfunction; Humans; Imidazoles; Male; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Topics: Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Erectile Dysfunction; Germany; Health Surveys; Humans; Imidazoles; Male; Middle Aged; Penile Erection; Piperazines; Quality of Life; Sulfones; Triazines; Vardenafil Dihydrochloride

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Sulfones; Triazines; Vardenafil Dihydrochloride

Vardenafil is a potent selective and reversible inhibitor of the cGMP phosphodiesterase type 5 that has been shown to improve erectile function in men. Vardenafil is usually well tolerated; the most common adverse events are headache, flushing, rhinitis, sinusitis and dyspepsia. We report a case of a 48-year-old man with an acute episode of widespread urticaria following vardenafil consumption and in absence of other identifiable causative factors. The patient had no previous episodes of urticaria. This appears to be the first report of urticaria associated with vardenafil.

Topics: Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Triazines; Urticaria; Vardenafil Dihydrochloride

Vardenafil is a potent and highly selective phosphodiesterase type 5 (PDE5) inhibitor with a potency about 10-fold higher than sildenafil. Vardenafil can significantly improve erectile function and works rapidly. Vardenafil is a PDE5 inhibitor with the fastest onset of action among its kind so far found and works as early as 10 minutes after oral administration, providing patients with penile erection sufficient to complete an intercourse. The absolute oral bioavailability is about 15%. Vardenafil is rapidly absorbed with a median tmax of 0.7 h and a terminal half-life (t1/2) of more than 4 h. The observed pharmacodynamic properties, pharmacokinetic characteristics and good safety and tolerability profile showed that vardenafil treatment provides an effective and generally well tolerated treatment for ED.

Topics: Adolescent; Adult; Aged; Animals; Erectile Dysfunction; Half-Life; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Rabbits; Sildenafil Citrate; Sulfones; Triazines; Vardenafil Dihydrochloride

A Micellar electrokinetic capillary chromatography method is proposed for the determination of sildenafil, vardenafil and tadalafil, which are employed in oral therapy for erectile dysfunction. Optimum conditions for the separation were investigated. A background electrolyte solution consisting of 10 mM phosphate buffer adjusted to pH 12.0, sodium dodecyl sulfate (SDS) 25 mM, hydrodynamic injection, and 25 kV as separation voltage were used. Relative standard deviations (R.S.D.s) were 1.0, 1.0, 0.4% and 2.9, 2.9, 1.9% for migration time and corrected peak area (CPA) (n = 9) for sildenafil, vardenafil and tadalafil, respectively. Detection limits obtained for the three drugs ranged from 0.19 to 0.61 mg L(-1). A linear concentration range between 1 and 20 mg L(-1) was obtained. A ruggedness test of this method was checked using the fractional factorial model of Plackett-Burman, in which the influence of six factors at three different levels was tested on different electrophoretic results: resolution and corrected peak area. The statistical evaluation of the electrophoretic results was achieved by Youden and Steiner method. The described method is rapid, sensitive and rugged and it was tested in the pharmaceutical formulations analysis obtaining recoveries between 98 and 107% respect to the nominal content.

Topics: Carbolines; Chromatography, Micellar Electrokinetic Capillary; Erectile Dysfunction; Humans; Imidazoles; Male; Piperazines; Purines; Reproducibility of Results; Sensitivity and Specificity; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Topics: Carbolines; Contraceptives, Oral; Erectile Dysfunction; Erotica; Female; Germany; History, 20th Century; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Photography; Piperazines; Purines; Sexual Behavior; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Vardenafil is a new type of PDE5 inhibitor (PDE5I) with great inhibiting potential on PDE5 (IC50: 0.01 nmol/L) for enhancing erectile function. International and domestic clinical studies showed it to be safe and effective in treating ED with mild temporary side effects such as headache, dizziness, flushing and rhinitis. In this paper we reviewed the cardiovascular safety of vardenafil. Studies showed that clinical dosage of vardenafil could decrease the systematic arterial blood pressure mildly (< 10 mmHg) , however, it did not interact in a potentially hazardous way with antihypertensive or antianginal therapy, with the exception of organic nitrates. Vardenafil slightly prolonged the QT interval (QTc) in cardiac repolarization, but with no evidence to prove that it could cause arrhythmia in clinical studies. The rates and categories of cardiovascular adverse events of vardenafil therapy were not significantly different from placebo in 5 clinical trials. Present studies demonstrated that clinical dosage of vardenafil appeared generally well tolerated in most patients with chronic and stable cardiovascular disease and it was an ideal drug for the first line treatment of ED.

Topics: Adult; Blood Pressure; Erectile Dysfunction; Heart; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Safety; Sulfones; Triazines; Vardenafil Dihydrochloride

The prevalence of erectile dysfunction (ED) is higher in diabete patients than in non-diabete men. Moreover, the treatment of ED is more challenging in men with diabetes. Vardenafil, a novel and highly selective phosphodiesterase 5 inhibitor, is the first line therapy for the broad ED population. Recent large-scale clinical trials indicated that vardenafil improved erectile function in ED men with diabetes regardless of the baseline ED severity and plasma HbA1c levels, and it was generally well tolerated.

Topics: Diabetes Complications; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To evaluate the reliability of vardenafil efficacy and tolerability within 12 weeks in a broad population of men with erectile dysfunction (ED).. In a retrospective analysis of two pivotal, Phase III, randomized, double-blind, placebo-controlled trials conducted in 107 centers, 1650 men aged 18 years or older with ED received vardenafil 5 mg, 10 mg, or 20 mg on demand for 12 to 26 weeks. Outcome measures included the first-time and subsequent overall success rate until week 12 for diary entries regarding vaginal penetration (Sexual Encounter Profile [SEP]-2), erection maintenance (SEP-3), satisfaction with erection hardness, and overall satisfaction with the sexual experience. Mean efficacy was calculated for each patient during 12 weeks and then averaged for all patients within each treatment group.. At baseline, the intention-to-treat population had moderate ED (International Index of Erectile Function-Erectile Function domain score of 13). For SEP-2 (penetration), the first-attempt and subsequent success rate was 44% and 74% for placebo, 71% and 81% for vardenafil 5 mg, 76% and 86% for vardenafil 10 mg, and 76% and 91% for vardenafil 20 mg, respectively. For SEP-3 (maintenance), first-attempt and subsequent success rate was 25% and 56% for placebo, 51% and 76% for vardenafil 5 mg, 65% and 76% for vardenafil 10 mg, and 59% and 84% for vardenafil 20 mg, respectively. For overall satisfaction with the sexual experience, the first-attempt and subsequent success rate was 19% and 48% for placebo, 48% and 68% for vardenafil 5 mg, 57% and 72% for vardenafil 10 mg, and 56% and 79% for vardenafil 20 mg, respectively. The reliability of vardenafil was similar or slightly greater in sildenafil-naive subjects compared with prior sildenafil responders. The most common adverse events were mild-to-moderate headache, flushing, and rhinitis.. Vardenafil provides reliable efficacy for key erectile function parameters important to patients when continuing oral treatment for ED.

Topics: Clinical Trials, Phase III as Topic; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Randomized Controlled Trials as Topic; Retrospective Studies; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Selective serotonin reuptake inhibitors (SSRIs) are associated with a high incidence of impotence. Paroxetine is an extensively used SSRI that has been shown to impair erectile function in patients, to induce erectile dysfunction and to inhibit nitric oxide synthase (NOS) activity and NO production in animal models. NO is a key mediator of penile erection. Vardenafil is a type 5 phosphodiesterase inhibitor that potentiates NO-mediated responses in isolated trabecular smooth muscle and penile erection in men in clinical trials. The aim of this study was to evaluate the effects of vardenafil on the impairment of erectile responses produced by paroxetine in the rat model. Application of cavernosal nerve electrical stimulation (CNES) produced frequency-related intracavernosal pressure (ICP) increases, which were inhibited by the NOS inhibitor N(G)-nitro-L-arginine (0.3 mg/kg) and potentiated by vardenafil (0.3 mg/kg). Acute paroxetine treatment (10 mg/kg) significantly reduced ICP-responses to CNES. This inhibition was completely reversed by vardenafil (0.3 mg/kg) administration. The results show that the erectile dysfunction induced by paroxetine in rats can be effectively treated with vardenafil, suggesting that the use of this compound could be a reasonable therapeutic approach to treating erectile dysfunction associated with SSRI administration.

Topics: Animals; Electric Stimulation; Erectile Dysfunction; Imidazoles; Injections, Intravenous; Male; Paroxetine; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Sulfones; Triazines; Vardenafil Dihydrochloride

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; United Kingdom; Vardenafil Dihydrochloride

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Clinical Trials as Topic; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Topics: Advertising; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Clinical Trials as Topic; Cyclic Nucleotide Phosphodiesterases, Type 5; Diabetes Complications; Diabetic Angiopathies; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors; Erectile Dysfunction; Fees, Pharmaceutical; Humans; Imidazoles; Male; Phosphoric Diester Hydrolases; Piperazines; Prostatectomy; Sulfones; Triazines; Vardenafil Dihydrochloride

Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has become a first-line therapy for diabetic patients with erectile dysfunction (ED). The efficacy in this subgroup, based on the Global Efficacy Question, is 56% vs 84% in a selected group of non-diabetic men with ED. Two novel PDE5 inhibitors, tadalafil (Lilly ICOS) and vardenafil (Bayer), have recently completed efficacy and safety clinical trials in 'general' and diabetic study populations and are now candidates for US FDA approval. A summary analysis of the phase three clinical trials of sildenafil, tadalafil and vardenafil in both study populations is presented to provide a foundation on which the evaluation of the role of the individual PDE5 inhibitors for the treatment of patients with ED and DM can be built.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Carbolines; Clinical Trials, Phase III as Topic; Cyclic Nucleotide Phosphodiesterases, Type 5; Diabetes Complications; Erectile Dysfunction; Humans; Imidazoles; Male; Multicenter Studies as Topic; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Diabetes Complications; Erectile Dysfunction; Humans; Imidazoles; Impotence, Vasculogenic; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Risk Factors; Sulfones; Triazines; Vardenafil Dihydrochloride

Topics: Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Placebos; Randomized Controlled Trials as Topic; Sulfones; Triazines; Vardenafil Dihydrochloride

Topics: Erectile Dysfunction; Humans; Imidazoles; Male; Penile Erection; Piperazines; Purines; Sildenafil Citrate; Sulfones; Triazines; Vardenafil Dihydrochloride; Vasodilator Agents

Tadalafil is an inhibitor of phosphodiesterase type 5, and is currently undergoing regulatory review in the US and in Europe. Its chemical structure is significantly different from sildenafil, and in vitro studies confirm significant potency for PDE5 inhibition, with little activity against most of the other isoforms of the enzyme including PDE6, which is the isoform of the enzyme found within the retina. The half-life of tadalafil is 17.5 hours and clinical studies suggest significant activity 24 hours post-dosing. As with sildenafil, efficacy depends upon a normal sexual stimulus, and the drug can taken be as required. Tadalafil is effective in the treatment of men with erectile dysfunction, and it appears to have a relatively mild side-effect profile, with no visual side-effects noted.

Topics: Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Tadalafil; Triazines; Vardenafil Dihydrochloride

Topics: Canada; Carbolines; Diabetes Complications; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Topics: Adult; Aged; Clinical Trials, Phase II as Topic; Coitus; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome; Triazines; Vardenafil Dihydrochloride