mirodenafil and Erectile-Dysfunction

To systematically review evidence on the efficacy and safety of mirodenafil treatment in erectile dysfunction (ED) from randomised controlled trials.. We searched PubMed, Embase and the Cochrane Library database up to March 2013. Two authors independently assessed study quality and extracted data. All data were analyzed using RevMan 5.0. Outcome measures assessed were the International Index of Erectile Function (IIEF), erectile function domain (EFD) score (primary), the Sexual Encounter Profile questions 2 and 3, and the response to the Global Assessment Questionnaire and adverse effects (secondary).. A total of 374 participants from three randomized controlled trials were identified in this meta-analysis. After 12 weeks treatment, mirodenafil was found to be more effective than placebo, and tolerability was good. The pooled results showed that the IIEF EFD score for 100 mg mirodenafil group was higher than placebo group (MD = 8.13, 95%CI: 6.64-9.61, p < 0.00001) and the mirodenafil group was also higher than placebo group in the changes from baseline for the IIEF EFD score (MD = 7.32, 95%CI: 5.56-9.07, p < 0.00001), respectively. The most common drug-related adverse events were flushing and headache (mirodenafil versus placebo: 15.8% versus 3.2%, 3.1% versus 0%; respectively).. This meta-analysis suggested that mirodenafil is effective and well-tolerated therapy for ED.

Topics: Double-Blind Method; Erectile Dysfunction; Humans; Male; Multicenter Studies as Topic; Penile Erection; Phosphodiesterase 5 Inhibitors; Pyrimidinones; Randomized Controlled Trials as Topic; Severity of Illness Index; Sulfonamides; Treatment Outcome

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

We aimed to evaluate whether changes in urinary and sexual function can influence health-related quality of life.. Out of 54 recruited patients, 36 were enrolled, and data for 30 participants with erectile dysfunction were available. At baseline and after 1 and 2 months, each participant completed the International Index of Erectile Function (IIEF-15), the International Prostate Symptom Score (IPSS) and the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36). Uroflowmetry, post-voiding residual volume and the nocturnal penile tumescence (NPT) test were performed at baseline and at the study's conclusion.. Compared with baseline, the IPSS, IIEF-15, peak urinary flow rate, NPT parameters and mental component of the SF-36 exhibited significant improvement at the study's conclusion. Among the symptomatic parameters, the changes in the storage and erectile function parameters contributed significantly to the change in the mental component score on the SF-36 (p = 0.007, R(2) = 0.502).. The daily administration of low-dose mirodenafil (50 mg) produced improvements in urinary and erectile function with or without sexual stimulation. Furthermore, this therapy enhanced the mental component of health-related quality of life by improving storage and erectile symptoms.

Topics: Adult; Erectile Dysfunction; Humans; Lower Urinary Tract Symptoms; Male; Middle Aged; Penile Erection; Phosphodiesterase 5 Inhibitors; Prospective Studies; Prostate; Pyrimidinones; Quality of Life; Sulfonamides; Surveys and Questionnaires; Treatment Outcome; Urinary Tract; Urodynamics

We evaluated the improvement in erectile dysfunction and lower urinary tract symptoms as well as the safety of once daily administration of 50 mg mirodenafil in men with erectile dysfunction.. A total of 226 patients visited for treatment of erectile dysfunction and were recruited for the study. Of these men 180 met the study inclusion criteria after completing a 2-week screening period (visit [V]1). The patients were randomly allocated into 2 groups. Group 1 (90 patients) received 50 mg mirodenafil once daily and group 2 (90 patients) received a placebo daily. Blood pressure, heart rate, IIEF-5 (5-item version of the International Index of Erectile Function), and SEP (Sexual Encounter Profile) questions 2 and 3 were assessed at 4 (V2), 8 (V3) and 12 weeks after the start of treatment (V4). I-PSS (International Prostate Symptom Score), maximal flow rate and post-void residual volume were also assessed for the evaluation of lower urinary tract symptoms.. Of the 180 patients 71 in group 1 and 63 in group 2 completed the 12-week clinical trial. IIEF-5 and I-PSS significantly improved in group 1 (p <0.001 for both). Facial flushing was the most common adverse effect, followed by headaches. Notably there were no statistically significant differences in either of the variables related to the cardiovascular system.. Once daily administration of 50 mg mirodenafil was efficacious and safe for the treatment of erectile dysfunction and lower urinary tract symptoms.

Topics: Administration, Oral; Adult; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Erectile Dysfunction; Humans; Male; Middle Aged; Penile Erection; Phosphodiesterase 5 Inhibitors; Pyrimidinones; Sulfonamides; Treatment Outcome; Young Adult

A high-sensitivity LC/MS/MS method was developed and validated for the simultaneous determination of mirodenafil and its major metabolite, SK-3541, in human plasma. Mirodenafil, SK-3541, and udenafil as an internal standard were extracted from plasma samples with methyl tert-butyl ether. Chromatographic separation was performed on a Luna phenyl-hexyl column (100 × 2.0 mm) with an isocratic mobile phase consisting of 5 mM ammonium formate and ACN (23:77, v/v) at a flow rate of 0.35 mL/min. Detection and quantification were performed using a mass spectrometer in selected reaction monitoring mode with positive ESI at m/z 532.3 → 296.1 for mirodenafil, m/z 488.1 → 296.1 for SK-3541, and m/z 517.3 → 283.2 for udenafil. The calibration curves were linear over a concentration range of 2-500 pg/mL using 0.5 mL plasma for the microdose of mirodenafil (100 μg). Analytical method validation of the clinical dose (100 mg), with a calibration curve range of 2-500 ng/mL using 0.025-mL plasma, was also conducted. The other LC-MS/MS conditions were similar to those used for the microdosing. Each method was applied successfully to pharmacokinetic studies after a microdose or clinical dose of mirodenafil to six healthy Korean male volunteers.

Topics: Adult; Chromatography, High Pressure Liquid; Drug Dosage Calculations; Erectile Dysfunction; Humans; Male; Pyrimidines; Pyrimidinones; Sensitivity and Specificity; Sulfonamides; Tandem Mass Spectrometry; Young Adult

Mirodenafil is a recently developed oral phosphodiesterase type 5 inhibitor, which was observed to significantly improve erectile function and was well tolerated in men with broad-spectrum erectile dysfunction (ED).. To investigate the efficacy and safety of mirodenafil treatment compared with placebo in men taking at least one antihypertensive medication.. A multicenter, double-blind, placebo-controlled, parallel group, fixed-dose study was conducted with 109 subjects who were randomized to placebo or mirodenafil 100 mg for 12 weeks on an "as needed" basis.. The primary efficacy measures were the changes from baseline in sum of scores on International Index of Erectile Function-erectile function domain (IIEF-EF) questions 1 to 5 and 15 with treatment. The secondary efficacy measures included scores on IIEF question 3 and 4 (Q3 and Q4), all domain scores of IIEF, and Sexual Encounter Profile Question 2 and 3 (SEP2 and SEP3) along with responses to Global Assessment Question (GAQ) and Life Satisfaction Checklist (LSC). The safety assessments included laboratory tests, vital signs, 12-lead electrocardiogram recordings, and patients' reporting of adverse events.. The mirodenafil group showed significantly greater increase in IIEF-EF scores at 12 weeks compared with the placebo group (9.35 ± 6.86 vs. 2.66 ± 6.44, P<0.001). The mirodenafil group also demonstrated significantly greater improvement in scores of IIEF Q3 and Q4, other four domains of IIEF, SEP2, SEP3, and LSC along with percentages of patients responding positively to GAQ compared with the placebo group. During the study, no clinically significant changes were observed regarding blood pressure, heart rate, electrocardiographic findings, or laboratory values. Facial flushing and headache were the most common treatment-associated adverse events, which were mild or moderate in severity, resolving spontaneously.. Mirodenafil was effective and safe in men with ED concomitantly taking antihypertensive medications.

Topics: Antihypertensive Agents; Blood Pressure; Double-Blind Method; Electrocardiography; Erectile Dysfunction; Flushing; Headache; Heart Rate; Humans; Hypertension; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Pyrimidinones; Sulfonamides

Mirodenafil is a newly developed oral phosphodiesterase type 5 inhibitor, currently under investigation as a treatment for erectile dysfunction (ED).. We investigated the efficacy and safety of on demand mirodenafil therapy at fixed doses (50 and 100 mg) in Korean men with a broad range of ED.. A multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study was conducted with 223 subjects who were randomized to placebo or mirodenafil at fixed doses of 50 or 100 mg for 12 weeks on an "as needed" basis.. Primary efficacy measures were scores on the International Index of Erectile Function (IIEF) Question 3 (Q3) and Question 4 (Q4). Secondary efficacy measures included all domain scores of the IIEF, Sexual Encounter Profile Question 2 (SEP2), Sexual Encounter Profile Question 3 (SEP3), the Global Assessment Question (GAQ), and the Life Satisfaction Checklist (LSC). Safety assessments included laboratory tests, vital signs, physical examination, 12-lead electrocardiogram recordings, and patients' reporting of adverse events.. Mirodenafil 50 and 100 mg groups showed a significantly greater increase in IIEF Q3 (P = 0.0001, P < 0.0001, respectively) and Q4 scores (both P < 0.0001) at the end point compared with the placebo group. And mirodenafil in both doses significantly improved the scores of all five domains of the IIEF, SEP2, and SEP3 as well as the percentages of patients responding positively to the GAQ compared with the placebo group. As for LSC scores, the two mirodenafil groups showed significantly greater improvements in items regarding life as a whole, sexual life, and partner relationship than the placebo group. Most treatment-associated adverse events were of mild intensity, resolving spontaneously.. Mirodenafil, in doses of 50 or 100 mg, significantly improved erectile function and were well tolerated in a representative population of Korean men with broad-spectrum ED of various etiologies and severities.

Topics: Administration, Oral; Adult; Aged; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Humans; Korea; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Pyrimidinones; Sulfonamides; Treatment Outcome; Young Adult

Topics: Erectile Dysfunction; Humans; Male; Penile Erection; Pyrimidinones; Sulfonamides

Enhanced RhoA/Rho-kinase pathway plays anti-erectile role and is associated with reduced response to type 5 phosphodiesterase inhibitor (PDE5I) in diabetic animals. We tested whether adjunctive simvastatin to conventional insulin treatment would restore PDE5I-induced as well as basal erectile response in diabetic rat model of erectile dysfunction. Forty 8-week-old male Sprague-Dawley rats were equally divided into four groups, (n=10) i.e. the diabetic group (D), age-matched control (C), conventional insulin treatment (I) and adjunctive simvastatin to conventional insulin treatment (S). Following 10weeks of intraperitoneal injection of streptozotocin (STZ, 35mg/kg), the group I and S received insulin (10U NPH/day) for 4weeks. Concurrently, group S received simvastatin (20mg/kg/day). Following 14weeks of diabetes induction, basal and PDE5I (intravenous mirodenafil 1mg/kg)-elicited erectile response were assessed during cavernous nerve electrostimulation. Then, penile tissues were processed for molecular assessment. Although group I failed to restore basal and PDE5I-induced erectile response, group S showed normalized erectile responses. Furthermore, group I showed improvement of only eNOS-related pathway, whereas group S effectively controlled both eNOS-related and RhoA/Rho-kinase pathway. Conclusively, adjunctive use of simvastatin to conventional insulin treatment showed more effectiveness in restoring erectile responses of diabetic rats by controlling the RhoA/Rho-kinase pathway than conventional insulin treatment alone.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Erectile Dysfunction; Insulin; Male; Nitric Oxide Synthase Type III; Penile Erection; Phosphodiesterase 5 Inhibitors; Pyrimidinones; Rats; Rats, Sprague-Dawley; rho-Associated Kinases; rhoA GTP-Binding Protein; Simvastatin; Sulfonamides

The area under the curve (AUC) of mirodenafil after intravenous administration in diabetes mellitus induced by streptozotocin (DMIS) rats was significantly smaller (by 28.0 %) than the control value, and the AUC(SK3541)/AUC(mirodenafil) ratio was significantly greater (by 130 %) in DMIS rats. This may be explained by the significantly faster hepatic CL(int) of mirodenafil, owing to increased hepatic CYP1A, CYP2B1/2, CYP2D, and CYP3A expression, and a faster hepatic blood flow rate, compared with control values. The AUC of mirodenafil after oral administration was comparable between DMIS and control rats, possibly because of the comparable intestinal CL(int), which may be attributable to increased CYP1A2 expression and decreased CYP2D expression in the intestines of DMIS rats.

Topics: Administration, Oral; Animals; Area Under Curve; Diabetes Complications; Diabetes Mellitus, Experimental; Erectile Dysfunction; Infusions, Intravenous; Male; Pyrimidinones; Rats; Rats, Sprague-Dawley; Streptozocin; Sulfonamides

Mirodenafil (SK3530) is a new potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5). Recent clinical trials have demonstrated that mirodenafil is an effective treatment for erectile dysfunction. Its mechanism of action is enhancement of nitric oxide (NO) induced cGMP formation resulting in significant relaxation of the corpus cavernosum (CC). The aim of this study was to investigate the oral efficacy of mirodenafil in an acute spinal cord-injured rabbit model. Mirodenafil or sildenafil citrate was given orally to male rabbits with a surgical transection of the spinal cord at the L2-L4 lumbar vertebra or ischemic-reperfusion spinal cord injury (SCI). Erections were evaluated in a time-course manner by measuring the length of the uncovered penile mucosa. In the transection SCI model, penile erections were induced at 0.3, 1 and 3 mg/kg of mirodenafil but sildenafil only showed an erectile response at 3 mg/kg. The effects of 1 and 3 mg/kg of mirodenafil were significantly increased by intravenous injection of sodium nitroprusside (SNP), a nitric oxide donor. In the ischemic-reperfusion injury model, 3 mg/kg of either mirodenafil or sildenafil produced a penile erection response. After injection of SNP, the lengths of immediate penile erections were significantly increased in the 1 and 3 mg/kg mirodenafil and 3 mg/kg sildenafil groups. The onset of erectile activity was faster with mirodenafil than with sildenafil citrate. These results demonstrate that mirodenafil may be useful for treating erectile dysfunction in patients with a spinal cord injury.

Topics: Administration, Oral; Animals; Erectile Dysfunction; Male; Mucous Membrane; Penile Erection; Phosphodiesterase 5 Inhibitors; Pyrimidinones; Rabbits; Spinal Cord Injuries; Sulfonamides

The purpose of this paper is to characterize the cytochrome P450 (CYP) enzymes involved in the metabolism of a new oral erectogenic, mirodenafil, to a major circulating active metabolite, N-dehydroxyethyl-mirodenafil, and to investigate the inhibitory potential of mirodenafil on seven CYP enzymes in human liver microsomes. CYP3A4 was identified as the major enzyme and CYP2C8 as a minor enzyme responsible for mirodenafil N-dealkylation based on correlation analysis, inhibition studies, and cDNA-expressed CYP enzyme activities. Plasma concentrations of mirodenafil and its N-dealkylated metabolite could therefore change with co-administration of known CYP3A4 inducers or inhibitors. Mirodenafil inhibited CYP3A4, CYP2C19 and CYP2D6 activities with IC50 values of 15.6, 38.2 and 77.0 microM, respectively, in human liver microsomes. However, it is very unlikely that mirodenafil will significantly alter the clearance of other compounds metabolized by CYPs 1A2, 2A6, 2C8, 2C9, 2C19, 2D6 and 3A4 because the maximum plasma concentration of mirodenafil is 0.55 microM after oral dosing of mirodenafil (100 mg) in male volunteers.

Topics: Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Dealkylation; Dose-Response Relationship, Drug; Enzyme Inhibitors; Erectile Dysfunction; Humans; Kinetics; Male; Microsomes, Liver; Pyrimidinones; Substrate Specificity; Sulfonamides