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Vardenafil
Selected AbstractsEFFECT OF THE PHOSPHODIESTERASE 5 INHIBITORS SILDENAFIL, TADALAFIL AND VARDENAFIL ON RAT ANOCOCCYGEUS MUSCLE: FUNCTIONAL AND BIOCHEMICAL ASPECTSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2009Haroldo A Toque SUMMARY 1The anococcygeus muscle is part of the erectile machinery in male rodents. Phosphodiesterase (PDE) 5 inhibitors enhance and prolong the effects of cGMP, which has a key role in penile erection. The aim of the present study was to provide a functional and biochemical comparison of the three PDE5 inhibitors, namely sildenafil, tadalafil and vardenafil, in the rat anococcygeus muscle. 2Muscle strips were mounted in 4 mL organ baths and isometric force recorded. Levels of cGMP were measured using an enzyme immunoassay kit. Western blots were used to determine PDE5 protein expression. 3The PDE5 inhibitors concentration-dependently relaxed carbachol-precontracted anococcygeus muscle; however, vardenafil was more potent (pEC50 = 8.11 ± 0.05) than sildenafil (7.72 ± 0.06) or tadalafil (7.69 ± 0.05). Addition of NG -nitro- l -arginine methyl ester (100 µmol/L) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 µmol/L) to the organ baths caused significant rightward shifts in concentration,response curves for all PDE5 inhibitors. 4Sildenafil, tadalafil and vardenafil (all at 0.1 µmol/L) caused leftward shifts in the glyceryl trinitrate (GTN) concentration-response curves (by 4.0-, 3.7- and 5.5-fold, respectively). In addition, all three PDE5 inhibitors significantly potentiated relaxation responses to both GTN (0.01,10 µmol/L) and electrical field stimulation (EFS; 1,32 Hz), with vardenafil having more pronounced effects. 5All three PDE5 inhibitors reduced EFS-evoked contractions in a concentration-dependent manner over the concentration range 0.001,1 µmol/L. There were no significant differences between the effects of the three PDE5 inhibitors. 6Vardenafil (0.01,0.1 µmol/L) was more potent in preventing cGMP degradation in vitro than sildenafil (0.01,0.1 µmol/L) and tadalafil (0.01,0.1 µmol/L). 7Under control conditions, the expression of PDE5 was higher in the anococcygeus muscle than in the corpus cavernosum. 8In conclusion, PDE5 inhibitors enhance exogenous and endogenous nitric oxide-mediated relaxation in the rat anococcygeus muscle. The potency of vardenafil was greater than that of either sildenafil or tadalafil. [source] Improvement in duration of erection following phosphodiesterase type 5 inhibitor therapy with vardenafil in men with erectile dysfunction: the ENDURANCE studyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 1 2009M. T. Rosenberg Summary Objective:, 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. Methods:, 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. Results:, 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. Conclusion:, Vardenafil 10-mg therapy provided a statistically superior duration of erection leading to successful intercourse in men with ED compared with placebo. [source] First-dose success with vardenafil in men with erectile dysfunction and associated comorbidities: RELY-IINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 11 2006L. VALIQUETTE Summary First-dose success of phosphodiesterase type 5 (PDE5) inhibitors may be adversely affected in patients with comorbidities. This article reports first-dose success rates for vardenafil 10 mg in men with erectile dysfunction (ED) and associated comorbidities who participated in the challenge phase of the Reliability , Vardenafil for Erectile Dysfunction I study. This study involved an open-label, single-dose, 1-week challenge period where patients who achieved SEP-2 (penetration) success were randomised to vardenafil 10 mg or placebo for 12 weeks in a double-blind manner. The first-dose success rates for SEP-2 and SEP-3 (maintenance of erection to completion of intercourse) were stratified according to comorbidities. Safety was assessed using adverse events (AEs). Of 600 men who received a single 10 mg dose of vardenafil, 32% had hypertension, 16% had diabetes and 19% had dyslipidaemia. Vardenafil demonstrated overall effectiveness, including first-dose SEP-2 and SEP-3 success rates in patients with and without specific comorbidities. Initial overall success rates for SEP-2 and SEP-3 during the challenge phase were 87% and 74% respectively. First-dose SEP-2 and SEP-3 success rates were 84% and 66% in men with hypertension (n = 191); 84% and 72% in men with dyslipidaemia (n = 116); and 75% and 58% in men with diabetes (n = 95). Vardenafil was well tolerated and most AEs, including the most frequently reported flushing (3.5%), were mild to moderate in intensity. Vardenafil 10 mg is generally well tolerated and efficacious, providing first-dose success with a consistently high rate of reliability of penetration and maintenance of erection in men with ED and associated comorbidities. [source] Vardenafil , PDE5 inhibitor number 3INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 3 2004Graham Jackson Editor [source] Efficacy of Phosphodiesterase Type 5 Inhibitor Treatment in Men with Erectile Dysfunction and Dyslipidemia: A Post Hoc Analysis of the Vardenafil Statin StudyTHE JOURNAL OF SEXUAL MEDICINE, Issue 5 2010Martin M. Miner MD ABSTRACT Introduction., Dyslipidemia occurs often in subjects with erectile dysfunction (ED), but there is little information about how this condition affects ED treatment responses. Aim., To determine whether low-density lipoprotein cholesterol (LDL-C) levels, total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio; or the presence of metabolic syndrome influenced efficacy of vardenafil in men with ED and dyslipidemia. Methods., Post hoc subgroup analysis of a 12-week study of the influence of lipid levels and presence of metabolic syndrome on the efficacy of vardenafil as measured by International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, responses to Sexual Encounter Profile (SEP) SEP2 and SEP3 questions, duration of erection leading to successful intercourse, and erection duration regardless of the answer to SEP3. Lipid values were obtained at study start, after patients had received at least 3 months of therapy with a statin. Main Outcome Measures., Outcomes in subjects with LDL-C <100, ,100 to <130, or ,130 mg/dL [<2.59, ,2.59 to <3.36, or ,3.36 mmol/L]; TC/HDL-C ratio <3.5 vs. ,3.5, and presence or absence of metabolic syndrome. Results., Vardenafil improved all endpoints evaluated compared with placebo in all subgroups, however, nominally significant treatment by subgroup interaction terms did not follow a distinct pattern. Increasing LDL-C (P = 0.033), but not TC/HDL-C ratio or metabolic syndrome, was associated with an increase in treatment response measured by the IIEF-EF domain score. Responses to SEP3 were nominally influenced by LDL-C levels (P = 0.019), but were not significantly influenced by TC/HDL-C ratio, or the metabolic syndrome. Only higher TC/HDL-C ratios (,3.5) were associated with larger treatment differences in duration of erection leading to successful intercourse (P = 0.028). Conclusions., Vardenafil was effective in men with dyslipidemia regardless of LDL-C levels, TC/HDL-C ratio, and/or presence of metabolic syndrome. Despite the known presence of ED and dyslipidemia, other cardiovascular risk factors were apparently not aggressively managed. Miner MM, Barnes A, and Janning S. Efficacy of phosphodiesterase type 5 inhibitor treatment in men with erectile dysfunction and dyslipidemia: A post hoc analysis of the vardenafil statin study. J Sex Med 2010;7:1937,1947. [source] Real-Life Safety and Efficacy of Vardenafil in the Treatment of Erectile Dysfunction,Results from 30,010 U.S. PatientsTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2007Eric Cheng MD ABSTRACT Introduction., 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). Aim., This study was conducted to evaluate real-life efficacy, safety, and acceptance of vardenafil in men with ED. Methods., 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. Main Outcome Measures., 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). Results., 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. Conclusions., 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. Cheng E. Real-life safety and efficacy of vardenafil in the treatment of erectile dysfunction,Results from 30,010 U.S. patients. J Sex Med 2007;4:432,439. [source] Vardenafil Restores Erectile Function to Normal Range in Men with Erectile DysfunctionTHE JOURNAL OF SEXUAL MEDICINE, Issue 1 2007Harin Padma-Nathan MD ABSTRACT Introduction., 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). Aim., To assess the ability of vardenafil to restore normal erectile function in men with general ED. Methods., 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. Main Outcome Measure., In this retrospective analysis, the percentage of patients "returning to normal" erectile function at week 12 (as defined by scores ,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. Results., 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 ,65 years, and 43% of men with ED of ,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 ,26 ranged from 87% to 95%. Conclusion., Vardenafil improves the IIEF-EF domain score to the normal range in a substantial proportion of men with ED. Padma-Nathan H, Montorsi F, Giuliano F, Meuleman E, Auerbach S, Eardley I, McCullough A, Homering M, and Segerson T for the North American and European Vardenafil Study Group. Vardenafil restores erectile function to normal range in men with erectile dysfunction. J Sex Med 2007;4:152,161. [source] Improving the Sexual Quality of Life of Couples Affected by Erectile Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Trial of VardenafilTHE JOURNAL OF SEXUAL MEDICINE, Issue 5 2005William A. Fisher PhD ABSTRACT Introduction., 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. Aim., 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. Methods., This was a randomized, double-blind, multicenter, flexible-dose, parallel-group comparison of vardenafil vs. placebo for 12 weeks in men (,18 years) with ED of ,,6 months duration, and their female partners. Main Outcome Measures., 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. Results., 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. Conclusions., Vardenafil improved erectile function in men with ED and improved the sexual quality of life of the couple. Fisher WA, Rosen RC, Mollen M, Brock G, Karlin G, Pommerville P, Goldstein I, Bangerter K, Bandel T-J, Derogatis LR, and Sand M for the Vardenafil Study Group. Improving the sexual quality of life of couples affected by erectile dysfunction: a double-blind, randomized, placebo-controlled trial of vardenafil. J Sex Med 2005;2:699,708. [source] Safety and efficacy of vardenafil versus sertraline in the treatment of premature ejaculation: a randomised, prospective and crossover studyANDROLOGIA, Issue 3 2009M. J. Mathers Summary 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. [source] Effects of chronic treatment with vardenafil, a phosphodiesterase 5 inhibitor, on female rat bladder in a partial bladder outlet obstruction modelBJU INTERNATIONAL, Issue 7 2009Seiji Matsumoto OBJECTIVES To investigate whether vardenafil, a phosphodiesterase 5 (PDE-5) inhibitor, would protect the bladder from decompensatory changes in a 4-week rat bladder outlet obstruction (BOO) model, as evidence has been accumulating that PDE-5 inhibitors improve lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS In all, 50 12-week-old female Sprague-Dawley rats were divided into five equal groups; group 1, sham operated vehicle control rats; group 2, BOO vehicle rats; group 3,5, BOO rats given oral vardenafil at 5, 20, 80 mg/L, respectively. Vardenafil was given in drinking water from the day of surgery. At 4-weeks after the introduction of BOO, vardenafil was washed-out by giving water for 24,48 h, and then the bladder was excised and dissected into four longitudinal strips for isometric organ-bath assay. Contractile responses of bladder strips to electrical field stimulation (EFS), carbachol and KCl was determined for each group. RESULTS BOO induced a significant increase in bladder weight in group 2 compared with group 1. Bladder weights of groups 3,5 were not significantly different from that of group 2. The contractile forces in response to EFS, carbachol and KCl in group 2 were 30.7,51.7% of those in group 1. Vardenafil treatment in groups 3,5 generally did not block the BOO-induced reduction of contractile force in the bladder strips. However, treatment with a high dose of vardenafil resulted in a significant increase in the contractile response to carbachol (78.4% group 5 vs 51.7% group 2). CONCLUSION Chronic treatment with a high dose of vardenafil protected the rat bladder from BOO-induced contractile dysfunction to carbachol. [source] Effects of long-term vardenafil treatment on the development of fibrotic plaques in a rat model of Peyronie's diseaseBJU INTERNATIONAL, Issue 3 2006MONICA G. FERRINI OBJECTIVES To determine whether the phosphodiesterase-5 (PDE5) inhibitor, vardenafil, given orally and in different regimens, has a similar effect to that of the PDE5 inhibitor sildenafil, which prevented the development of a Peyronie's disease (PD)-like plaque formation induced by injecting transforming growth factor ,1 (TGF-,1) into the tunica albuginea of the rat. MATERIALS AND METHODS Vardenafil was given to male rats (eight per group) either in the drinking water or as an oral instillation once daily, at ,,1 and ,,3 mg/kg/day for 45 days after one injection with TGF-,1 into the tunica albuginea, as an ,early preventive' treatment for TGF-,1-induced formation of a PD-like plaque. Other groups received the two doses of vardenafil only in the drinking water, starting with a well-formed plaque, for 42 days (,late, therapeutic' administration). Sections of penile tissue were stained histochemically or immunohistochemically, followed by quantitative image analysis for collagen/smooth muscle and collagen III/I ratios, myofibroblast content (,-smooth muscle actin), TGF-,1 expression, and apoptotic index. RESULTS Preventative treatment with vardenafil at the higher dose (both continuous and once-daily treatments) reduced the collagen/smooth muscle and collagen III/I ratios, and the numbers of myofibroblasts and TGF-,1-positive cells, and selectively increased the apoptotic index in the PD-like plaque. The lower dose was less effective, When vardenafil was given continuously in the drinking water for 41 days after the PD-like plaque was formed, there was only a partial reduction of the plaque. CONCLUSIONS Long-term oral treatment with vardenafil slows and reverses the early stages of an experimental PD-like plaque in the rat, and might ameliorate a more advanced plaque. [source] Improvement in duration of erection following phosphodiesterase type 5 inhibitor therapy with vardenafil in men with erectile dysfunction: the ENDURANCE studyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 1 2009M. T. Rosenberg Summary Objective:, 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. Methods:, 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. Results:, 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. Conclusion:, Vardenafil 10-mg therapy provided a statistically superior duration of erection leading to successful intercourse in men with ED compared with placebo. [source] First-dose success with vardenafil in men with erectile dysfunction and associated comorbidities: RELY-IINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 11 2006L. VALIQUETTE Summary First-dose success of phosphodiesterase type 5 (PDE5) inhibitors may be adversely affected in patients with comorbidities. This article reports first-dose success rates for vardenafil 10 mg in men with erectile dysfunction (ED) and associated comorbidities who participated in the challenge phase of the Reliability , Vardenafil for Erectile Dysfunction I study. This study involved an open-label, single-dose, 1-week challenge period where patients who achieved SEP-2 (penetration) success were randomised to vardenafil 10 mg or placebo for 12 weeks in a double-blind manner. The first-dose success rates for SEP-2 and SEP-3 (maintenance of erection to completion of intercourse) were stratified according to comorbidities. Safety was assessed using adverse events (AEs). Of 600 men who received a single 10 mg dose of vardenafil, 32% had hypertension, 16% had diabetes and 19% had dyslipidaemia. Vardenafil demonstrated overall effectiveness, including first-dose SEP-2 and SEP-3 success rates in patients with and without specific comorbidities. Initial overall success rates for SEP-2 and SEP-3 during the challenge phase were 87% and 74% respectively. First-dose SEP-2 and SEP-3 success rates were 84% and 66% in men with hypertension (n = 191); 84% and 72% in men with dyslipidaemia (n = 116); and 75% and 58% in men with diabetes (n = 95). Vardenafil was well tolerated and most AEs, including the most frequently reported flushing (3.5%), were mild to moderate in intensity. Vardenafil 10 mg is generally well tolerated and efficacious, providing first-dose success with a consistently high rate of reliability of penetration and maintenance of erection in men with ED and associated comorbidities. [source] Synthesis of [14C]-labelled vardenafil hydrochloride and metabolitesJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 11 2003D. Seidel Abstract For studies of pharmacokinetics and drug metabolism of the new orally active, selective phosphodiesterase type V (PDE V) inhibitor vardenafil (Levitra®), the 14C-labelled version was synthesised. Starting from the cyanation of 2-iodophenol with K14CN, an 8-step synthesis led to two batches with 0.727 g (2.857 GBq) and 2.199 g (5.497 GBq) of [triazinone- 14C]vardenafil hydrochlo-ride with different specific radioactivities. The label was located in position 2 of the imidazotriazinone moiety. Several carbon-14 labelled metabolites were synthesised as reference compounds for metabolism studies. Copyright © 2003 John Wiley & Sons, Ltd. [source] Simultaneous determination of yohimbine, sildenafil, vardenafil and tadalafil in dietary supplements using high-performance liquid chromatography-tandem mass spectrometryJOURNAL OF SEPARATION SCIENCE, JSS, Issue 14 2010Ying Zhang Abstract 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 C18 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. [source] A gas chromatography/mass spectrometry method for the determination of sildenafil, vardenafil and tadalafil and their metabolites in human urineRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 11 2010Sabina Strano-Rossi Sildenafil (SDF), vardenafil (VDF) and tadalafil (TDF) are phosphodiesterase type 5 enzyme inhibitors (PDE5Is), used in the treatment of erectile disorders and to improve breathing efficiency in pulmonary hypertension. The increasing incidence of their use among young athletes has drawn the attention of the anti-doping authorities to the possible abuse of PDE5Is by athletes due to their pharmacological activities. This paper describes a method for the determination in urine of PDE5Is and their metabolites by gas chromatography/mass spectrometry (GC/MS) after liquid/liquid extraction of the analytes from urine and derivatisation to obtain trimethylsilyl derivatives. The metabolic profile was studied on real samples collected from subjects taking PDE5Is (Viagra®, Levitra® or Cialis®); the main urinary metabolites were identified and their MS fragmentation characterized. The sample pre-treatment and GC/MS conditions for the detection of the metabolites have been optimised. A method for their preliminary screening and subsequent confirmation is described that takes into account the general requirements of a routine doping analysis to be used for the screening of large numbers of samples. The main metabolites identified can be included in a general purpose screening method and all the metabolites in a more specific confirmation method. The method developed has been applied for the screening of PDE5Is in 5000 urine samples. Based on the obtained results, the proposed method appears to be of practical use in analytical and forensic toxicology, including doping analysis. Copyright © 2010 John Wiley & Sons, Ltd. [source] Efficacy of Phosphodiesterase Type 5 Inhibitor Treatment in Men with Erectile Dysfunction and Dyslipidemia: A Post Hoc Analysis of the Vardenafil Statin StudyTHE JOURNAL OF SEXUAL MEDICINE, Issue 5 2010Martin M. Miner MD ABSTRACT Introduction., Dyslipidemia occurs often in subjects with erectile dysfunction (ED), but there is little information about how this condition affects ED treatment responses. Aim., To determine whether low-density lipoprotein cholesterol (LDL-C) levels, total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio; or the presence of metabolic syndrome influenced efficacy of vardenafil in men with ED and dyslipidemia. Methods., Post hoc subgroup analysis of a 12-week study of the influence of lipid levels and presence of metabolic syndrome on the efficacy of vardenafil as measured by International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, responses to Sexual Encounter Profile (SEP) SEP2 and SEP3 questions, duration of erection leading to successful intercourse, and erection duration regardless of the answer to SEP3. Lipid values were obtained at study start, after patients had received at least 3 months of therapy with a statin. Main Outcome Measures., Outcomes in subjects with LDL-C <100, ,100 to <130, or ,130 mg/dL [<2.59, ,2.59 to <3.36, or ,3.36 mmol/L]; TC/HDL-C ratio <3.5 vs. ,3.5, and presence or absence of metabolic syndrome. Results., Vardenafil improved all endpoints evaluated compared with placebo in all subgroups, however, nominally significant treatment by subgroup interaction terms did not follow a distinct pattern. Increasing LDL-C (P = 0.033), but not TC/HDL-C ratio or metabolic syndrome, was associated with an increase in treatment response measured by the IIEF-EF domain score. Responses to SEP3 were nominally influenced by LDL-C levels (P = 0.019), but were not significantly influenced by TC/HDL-C ratio, or the metabolic syndrome. Only higher TC/HDL-C ratios (,3.5) were associated with larger treatment differences in duration of erection leading to successful intercourse (P = 0.028). Conclusions., Vardenafil was effective in men with dyslipidemia regardless of LDL-C levels, TC/HDL-C ratio, and/or presence of metabolic syndrome. Despite the known presence of ED and dyslipidemia, other cardiovascular risk factors were apparently not aggressively managed. Miner MM, Barnes A, and Janning S. Efficacy of phosphodiesterase type 5 inhibitor treatment in men with erectile dysfunction and dyslipidemia: A post hoc analysis of the vardenafil statin study. J Sex Med 2010;7:1937,1947. [source] Phosphodiesterase Type 5 Inhibitors and Female Sexual Response: Faulty Protocols or Paradigms?THE JOURNAL OF SEXUAL MEDICINE, Issue 2pt2 2010Meredith L. Chivers PhD ABSTRACT Introduction., Phosphodiesterase type 5 inhibitors (PDE5), such as sildenafil, tadalafil, and vardenafil, have revolutionized the treatment of erectile dysfunction. Few successes, in contrast, have been reported for the use of these agents in treatment of sexual arousal problems in women. Aim., To review research examining efficacy of PDE5 in women, critique the methods and models employed, and integrate the findings within a broader, gender-specific understanding of female sexual response. Methods., A conceptual and methodological review of all published studies examining PDE5 efficacy in female samples. Main Outcome Measures., Study methods, populations, outcome measures, study results. Results., A total of 16 studies were reviewed. Studies using self-reported measures of sexual functioning showed mixed results whereas studies examining physiological effects of PDE5 on genital vasocongestion consistently report significant effects on genital sexual response. Conclusions., The lack of efficacy of PDE5 treatment in women is likely attributable to gender differences in the concordance between physiological and psychological components of sexual response. Discordance between genital and subjective measures of sexual response in women may be augmented by PDE5 effects on genital vasocongestion in some populations, rendering successful treatment unlikely via pharmacological treatment alone. Chivers M, and Rosen RC. PDE5 inhibitors and female sexual response: Faulty protocols or paradigms? J Sex Med 2010;7:858,872. [source] Characterization of Phosphodiesterase Type 5 Expression and Functional Activity in the Human Male Lower Urinary TractTHE JOURNAL OF SEXUAL MEDICINE, Issue 1pt1 2010Benedetta Fibbi MD ABSTRACT Introduction., Phosphodiesterase type 5 (PDE5) inhibitors ameliorate low urinary tract (LUT) symptoms in men with ED and symptomatic benign prostatic hyperplasia (BPH). PDE5 is highly expressed in rat and human bladder, where it regulates cyclic guanosine monophosphate (cGMP) degradation, muscle tone, and proliferation. Aim., To investigate PDE5 tissue distribution and activity in human LUT tissues (urethra, prostate, and bladder). Main Outcome Measures., PDE5 expression and activity were analyzed and compared within the same BPH patient in LUT tissues and in smooth muscle cells (SMCs) cultured from urethra, prostate, and bladder. Methods., In LUT tissues, PDE5 was localized by immunohistochemistry and mRNA expression by quantitative real-time polymerase chain reaction. Proliferation assay was used as readout of PDE5 activity, evaluated as ability of vardenafil to increase the antiproliferative effect of different nitric oxide (NO)/cGMP pathway activators [the PDE5-resistant cGMP analog Sp-8-Br-PET-cGMPS, the NO donor sodium nitroprusside (SNP), and the soluble guanylate cyclase (sGC) stimulator BAY 41-8543]. Results., In all the LUT tissues, PDE5 was immunolocalized in blood vessels and in muscular fibres, but not in epithelium. PDE5 mRNA expression was higher in urethra and bladder than in prostate SMC. The antiproliferative effect of Sp-8-Br-PET-cGMPS was similar in all LUT SMC. In prostatic SMC, SNP and BAY 41-8543 show a dose-dependent antiproliferative effect that resulted marginally enhanced by vardenafil. Conversely, in urethra and bladder SMC the antiproliferative effect of SNP and BAY 41-8543 was lower than in prostatic SMC, but it was significantly enhanced by vardenafil. In urethral and bladder cells vardenafil half-maximal response inhibiting concentration was in the subnanomolar range, whereas in prostate cells it resulted significantly higher. Conclusions., The highest expression and biological activity of PDE5 was found in bladder. However, a consistent PDE5 expression and activity was also found in prostatic urethra. In contrast, the prostate gland showed the lowest PDE5 abundance and cultures derived from this tissue were less sensitive to vardenafil. Fibbi B, Morelli A, Vignozzi L, Filippi S, Chavalmane A, De Vita G, Marini M, Gacci M, Vannelli GB, Sandner P, and Maggi M. Characterization of phosphodiesterase type 5 expression and functional activity in the human male lower urinary tract. J Sex Med 2010;7:59,69. [source] The Influence of Testosterone Combined with a PDE5-inhibitor on Cognitive, Affective, and Physiological Sexual Functioning in Women Suffering from Sexual DysfunctionTHE JOURNAL OF SEXUAL MEDICINE, Issue 3 2009Flip Van Der Made MD ABSTRACT Introduction., Women with female sexual dysfunction have a reduced sensitivity to sexual stimuli. Activation of central mechanisms may open a window for phosphodiesterase type 5 inhibitors (PDE5) to be effective; as a consequence, the combination of testosterone and a PDE5 inhibitor will restore sexual function. Aim., To demonstrate that the combination of testosterone and vardenafil will increase the sensitivity for sexual stimuli and will improve the desire and arousal components of the sexual response. Methods., In a double-blind randomly assigned placebo-controlled crossover design, 28 women with desire and/or arousal disorder underwent four different drug treatments on four separate experimental days. A masked version of the emotional Stroop task with sexual and nonsexual words was used to measure sensitivity for sexual content. Neutral and erotic film fragments were used to determine genital,physiological and subjective reactions. Main Outcome Measures., A masked version of the emotional Stroop task, vaginal pulse amplitude. For subjective measurement, responses were collected continuously with a lever and two self-report measures were used. Results., In two subgroups, which were differentiated on the basis of their initial preconscious attentional bias for sexual cues, a different sexual response profile was found. In an initially low-attention group, preconscious attentional bias for sexual cues increased under the testosterone condition. In these women, the combination of testosterone and vardenafil caused an improvement in genital response and subjective indices of sexual functioning. In the group that had initially a high attention for sexual cues, preconscious attentional bias for sexual cues decreased under the condition of testosterone. In these women, the combination of testosterone and vardenafil had no effect on any of the indices of their sexual functioning. Conclusion., In women suffering from low sexual desire,associated with low attention for sexual cues,the combination of testosterone and vardenafil may be a promising new treatment. van der Made F, Bloemers J, Yassem WE, Kleiverda G, Everaerd W, van Ham D, Olivier B, Koppeschaar H, and Tuiten A. The influence of testosterone combined with a PDE5-inhibitor on cognitive, affective, and physiological sexual functioning in women suffering from sexual dysfunction. J Sex Med 2009;6:777,790. [source] Effect of Testosterone on Potassium Channel Opening in Human Corporal Smooth Muscle CellsTHE JOURNAL OF SEXUAL MEDICINE, Issue 4 2008Deok Hyun Han MD ABSTRACT Introduction., In humans, the role of testosterone in sexual functions, including sexual desire, nocturnal penile erections, and ejaculatory volume, has been relatively well established. However, the effects of testosterone on intrapenile structure in humans remains controversial. Aim., We assessed the direct effects of testosterone on potassium channels in human corporal smooth muscle cells, in an effort to understand the mechanisms inherent to the testosterone-induced relaxation of corporal smooth muscle cells at the cellular and molecular levels. Methods., We conducted electrophysiologic studies using cultured human corporal smooth muscle cells. We evaluated the effects of testosterone on potassium channels,BKCa and KATP channels,by determining the whole-cell currents and single-channel activities. For the electrophysiologic recordings, whole-cell and cell-attached configuration patch-clamp techniques were utilized. Main Outcome Measures., Changes in whole-cell currents and channel activities of BKCa and KATP channels by testosterone. Results., Testosterone (200 nM) significantly increased the single-channel activity of calcium-activated potassium (BKCa) channels and whole-cell K+ currents by 443.4 ± 83.4% (at +60 mV; N = 11, P < 0.05), and this effect was abolished by tetraethylammonium (TEA) (1 mM), a BKCa channel blocker. The whole-cell inward K+ currents of the KATP channels were also increased by 226.5 ± 49.3% (at ,100 mV; N = 7, P < 0.05). In the presence of a combination of vardenafil (10 nM) and testosterone (200 nM), the BKCa channel was activated to a significantly higher degree than was induced by testosterone alone. Conclusions., The results of patch-clamp studies provided direct molecular evidence that testosterone stimulates the activity of BKCa channels and KATP channels. An understanding of the signaling mechanisms that couple testosterone receptor activation to potassium channel stimulation will provide us with an insight into the cellular processes underlying the vasorelaxant effects of testosterone. Han DH, Chae MR, Jung JH, So I, Park JK, and Lee SW. Effect of testosterone on potassium channel opening in human corporal smooth muscle cells. J Sex Med 2008;5:822,832. [source] Real-Life Safety and Efficacy of Vardenafil in the Treatment of Erectile Dysfunction,Results from 30,010 U.S. PatientsTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2007Eric Cheng MD ABSTRACT Introduction., 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). Aim., This study was conducted to evaluate real-life efficacy, safety, and acceptance of vardenafil in men with ED. Methods., 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. Main Outcome Measures., 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). Results., 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. Conclusions., 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. Cheng E. Real-life safety and efficacy of vardenafil in the treatment of erectile dysfunction,Results from 30,010 U.S. patients. J Sex Med 2007;4:432,439. [source] Vardenafil Restores Erectile Function to Normal Range in Men with Erectile DysfunctionTHE JOURNAL OF SEXUAL MEDICINE, Issue 1 2007Harin Padma-Nathan MD ABSTRACT Introduction., 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). Aim., To assess the ability of vardenafil to restore normal erectile function in men with general ED. Methods., 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. Main Outcome Measure., In this retrospective analysis, the percentage of patients "returning to normal" erectile function at week 12 (as defined by scores ,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. Results., 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 ,65 years, and 43% of men with ED of ,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 ,26 ranged from 87% to 95%. Conclusion., Vardenafil improves the IIEF-EF domain score to the normal range in a substantial proportion of men with ED. Padma-Nathan H, Montorsi F, Giuliano F, Meuleman E, Auerbach S, Eardley I, McCullough A, Homering M, and Segerson T for the North American and European Vardenafil Study Group. Vardenafil restores erectile function to normal range in men with erectile dysfunction. J Sex Med 2007;4:152,161. [source] The Effect of Ovariectomy on Rat Vaginal Tissue Contractility and HistomorphologyTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2006F. Fatih Önol MD ABSTRACT Introduction., Ovarian hormones have an important role in age-related genital arousal disorders; however, our knowledge regarding possible vaginal wall morphology and contractility changes in low-hormonal states is limited. Aims., To investigate morphological and functional alterations in the vaginal tissue in a rat ovariectomy model and to show the differences between proximal and distal vagina. Methods., Six weeks following ovariectomy, vaginal tissues were examined under light and electron microscopy. Circularly cut distal and proximal tissues were studied in the organ bath under isometric tension and compared with age-matched controls. Contractile responses to electrical field stimulation (EFS), phenylephrine, carbachol, and the effects of alpha-1 and alpha-2 blockade on EFS-induced contractility were investigated. Relaxation responses to EFS and vardenafil were investigated in precontracted strips. Main Outcome Measures., Differences between control and ovariectomy groups in terms of vaginal tissue contractility and histomorphological properties. Results., Distal vagina showed different epithelial characteristics and a better-developed muscularis compared with proximal vagina. Ovariectomy caused thinning of the epithelium, severe degeneration in epithelial architecture, and smooth muscle atrophy. Contraction and relaxation responses of distal strips were significantly lower in ovariectomized rats. Contractile responses to neuropharmacological stimulation were insignificant in proximal strips of both groups. EFS-induced contractions in distal strips diminished significantly after alpha-1 and alpha-2 adrenergic blockade. EFS caused frequency-dependent relaxation responses in precontracted distal strips, which were significantly decreased after nitric oxide synthase inhibition. Conclusions., Ovariectomy causes significant alteration in rat vaginal tissue morphology and contractility. Contraction and relaxation responses of distal vagina are significantly greater compared with morphologically distinct proximal vagina. Alpha-1 and alpha-2 receptors are the main mediators of contraction in distal rat vaginal tissue whereas nitric oxide pathway may have at least a partial role in relaxation. Main mediators of the rat vaginal tissue relaxation and the effect of ovariectomy on this regulation are yet to be defined. Önol FF, Ercan F, and Tarcan T. The effect of ovariectomy on rat vaginal tissue contractility and histomorphology. J Sex Med 2006;3:233,241. [source] Improving the Sexual Quality of Life of Couples Affected by Erectile Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Trial of VardenafilTHE JOURNAL OF SEXUAL MEDICINE, Issue 5 2005William A. Fisher PhD ABSTRACT Introduction., 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. Aim., 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. Methods., This was a randomized, double-blind, multicenter, flexible-dose, parallel-group comparison of vardenafil vs. placebo for 12 weeks in men (,18 years) with ED of ,,6 months duration, and their female partners. Main Outcome Measures., 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. Results., 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. Conclusions., Vardenafil improved erectile function in men with ED and improved the sexual quality of life of the couple. Fisher WA, Rosen RC, Mollen M, Brock G, Karlin G, Pommerville P, Goldstein I, Bangerter K, Bandel T-J, Derogatis LR, and Sand M for the Vardenafil Study Group. Improving the sexual quality of life of couples affected by erectile dysfunction: a double-blind, randomized, placebo-controlled trial of vardenafil. J Sex Med 2005;2:699,708. [source] Safety and efficacy of vardenafil versus sertraline in the treatment of premature ejaculation: a randomised, prospective and crossover studyANDROLOGIA, Issue 3 2009M. J. Mathers Summary 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. [source] Sexual functions of men with obstructive sleep apnoea syndrome and hypogonadism may improve upon testosterone administration: a pilot studyANDROLOGIA, Issue 3 2009V. N. Zhuravlev Summary 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. [source] Effects of chronic treatment with vardenafil, a phosphodiesterase 5 inhibitor, on female rat bladder in a partial bladder outlet obstruction modelBJU INTERNATIONAL, Issue 7 2009Seiji Matsumoto OBJECTIVES To investigate whether vardenafil, a phosphodiesterase 5 (PDE-5) inhibitor, would protect the bladder from decompensatory changes in a 4-week rat bladder outlet obstruction (BOO) model, as evidence has been accumulating that PDE-5 inhibitors improve lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS In all, 50 12-week-old female Sprague-Dawley rats were divided into five equal groups; group 1, sham operated vehicle control rats; group 2, BOO vehicle rats; group 3,5, BOO rats given oral vardenafil at 5, 20, 80 mg/L, respectively. Vardenafil was given in drinking water from the day of surgery. At 4-weeks after the introduction of BOO, vardenafil was washed-out by giving water for 24,48 h, and then the bladder was excised and dissected into four longitudinal strips for isometric organ-bath assay. Contractile responses of bladder strips to electrical field stimulation (EFS), carbachol and KCl was determined for each group. RESULTS BOO induced a significant increase in bladder weight in group 2 compared with group 1. Bladder weights of groups 3,5 were not significantly different from that of group 2. The contractile forces in response to EFS, carbachol and KCl in group 2 were 30.7,51.7% of those in group 1. Vardenafil treatment in groups 3,5 generally did not block the BOO-induced reduction of contractile force in the bladder strips. However, treatment with a high dose of vardenafil resulted in a significant increase in the contractile response to carbachol (78.4% group 5 vs 51.7% group 2). CONCLUSION Chronic treatment with a high dose of vardenafil protected the rat bladder from BOO-induced contractile dysfunction to carbachol. [source] Factors that predict changing the type of phosphodiesterase type 5 inhibitor medication among men in the UKBJU INTERNATIONAL, Issue 4 2007Philip D. Kell OBJECTIVE 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 AND METHODS 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). RESULTS 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). CONCLUSION Initiating ED therapy with sildenafil was associated with the lowest rate of PDE5 inhibitor switching, which might reflect treatment satisfaction and patient preference. [source] Effects of long-term vardenafil treatment on the development of fibrotic plaques in a rat model of Peyronie's diseaseBJU INTERNATIONAL, Issue 3 2006MONICA G. FERRINI OBJECTIVES To determine whether the phosphodiesterase-5 (PDE5) inhibitor, vardenafil, given orally and in different regimens, has a similar effect to that of the PDE5 inhibitor sildenafil, which prevented the development of a Peyronie's disease (PD)-like plaque formation induced by injecting transforming growth factor ,1 (TGF-,1) into the tunica albuginea of the rat. MATERIALS AND METHODS Vardenafil was given to male rats (eight per group) either in the drinking water or as an oral instillation once daily, at ,,1 and ,,3 mg/kg/day for 45 days after one injection with TGF-,1 into the tunica albuginea, as an ,early preventive' treatment for TGF-,1-induced formation of a PD-like plaque. Other groups received the two doses of vardenafil only in the drinking water, starting with a well-formed plaque, for 42 days (,late, therapeutic' administration). Sections of penile tissue were stained histochemically or immunohistochemically, followed by quantitative image analysis for collagen/smooth muscle and collagen III/I ratios, myofibroblast content (,-smooth muscle actin), TGF-,1 expression, and apoptotic index. RESULTS Preventative treatment with vardenafil at the higher dose (both continuous and once-daily treatments) reduced the collagen/smooth muscle and collagen III/I ratios, and the numbers of myofibroblasts and TGF-,1-positive cells, and selectively increased the apoptotic index in the PD-like plaque. The lower dose was less effective, When vardenafil was given continuously in the drinking water for 41 days after the PD-like plaque was formed, there was only a partial reduction of the plaque. CONCLUSIONS Long-term oral treatment with vardenafil slows and reverses the early stages of an experimental PD-like plaque in the rat, and might ameliorate a more advanced plaque. [source] | |||||||||||||