Udenafil Group Research Articles

Protective Effect of Udenafil Against Ischemia Reperfusion Injury Due to Testicular Torsion/Detorsion in Rat Model.

Testicular torsion causes migration of neutrophils to the ischemic region and formation of free oxygen radicals that have a critical effect on ischemic reperfusion (I/R) injury. Udenafil is a selective, strong, and reversible inhibitor of phosphodiesterase type enzyme. In our study, we evaluate the protective effect of udenafil against reperfusion injury due to I/R. Twenty-one male, adult, Wistar-Albino rats aged 8 months were randomly divided into three groups; sham, I/R, and I/R+udenafil. One hour before the detorsion operation, the sham and I/R groupssaline, and I/R+udenafil groups were administered 2 mg/kg udenafil intraperitoneally. Blood samples were collected to evaluate the inflammatory mediators. Spermatogenic factors were evaluated according to Johnsen criteria. Histopathological and molecular parameters from all groups were compared. Mean values of TNF-α and IL-1β in venous blood samples were calculated. We observed that TNF-a values were statistically significantly increased in the I/R group than those in sham groups, and these values were decreased with udenafil treatment Furthermore, the glutathione peroxidase (GPx) level was statistically significantly decreased in the I/R group, and treatment with udenafil prevented this decrease. Evaluation of spermatogenesis using the Johnsen scoring system showed no statistically significant difference in mean scores between the groups. We concluded that deterioration of biochemical and histopathological parameters are reversed, and injury due to I/R in testicle tissue may be decreased with udenafil treatment. Results of this experimental study show that efficacy of the udenafil treatment in testis torsion should be investigated.

Stimulating effects of vardenafil, tadalafil, and udenafil on vascular endothelial growth factor, angiogenesis, vitamin D3, bone morphogenic proteins in ovariectomized rats

Objective: This study investigated the effect of vardenafil, tadalafil, and udenafil from phosphodiesterase-5 inhibitors (PDE-5Is) on bone morphogenic-protein (BMP)2 and 4 levels, along with angiogenesis in ovariectomized rat’s kidney.Method: Rats were randomly divided into five groups (n = 10). Sham: abdomen was opened, and closed. OVX: ovaries were removed. OVX + vardenafil, OVX + tadalafil, and OVX + udenafil groups: ovaries were removed and closed, and after 6 months from postoperative, 10 mg/kg of vardenafil, tadalafil, and udenafil were administrated as daily a single-dose for 60 days, respectively. Histopathologic and immunohistochemical examinations were performed for angiogenesis, and biochemical analysis for vascular endothelial growth-factor (VEGF), VitaminD3, BMP2 and 4 levels in rat’s kidney.Results: VEGF, BMP2 and 4, VitaminD3, and angiogenesis were high in the all inhibitor groups compared with the sham and OVX (p < .05). However, BMP4 levels were only high in the OVX + tadalafil group (p < .05).Conclusion: The results indicated that vardenafil, udenafil, and especially tadalafil increased VEGF, BMP2, and VitaminD3 levels.

Effect of udenafil administration on postmicturition dribbling in men: a prospective, multicenter, double-blind, placebo-controlled, randomized clinical study

Purpose Postmicturition dribbling (PMD) is a stressful symptom in middle-aged men characterized by urinary leakage after the completion of normal voiding. Appropriate treatments have not yet been introduced. This study assessed the efficacy of treatment of PMD with 75 mg udenafil daily. Materials and Methods The study included 138 men with regular sexual lifestyles. The Hallym PMD questionnaire (HPMDQ) was used to assess PMD symptoms. After all basic examinations, patients were randomly assigned to either udenafil or placebo. Patients completed the surveys, uroflowmetry (UFM), a bladder scan, and the paper test during the follow-up visit. Results The mean age of the patients was 57.6 years. PMD with one of every three urinations was experienced by 59 patients (42.8%), whereas 45 patients (32.6%) experienced PMD with two of every three urinations. PMD with every urination was experienced by 34 patients (24.6%). More than half of the patients (89 patients, 65.4%) indicated that persistent PMD symptoms would likely result in moderate to severe discomfort in their daily activities. As time passed, the udenafil group showed significant improvement in PMD symptoms (p = 0.001). Conclusion Udenafil 75 mg once daily can be an effective treatment for patients with PMD symptoms.

The mechanism of attenuation of epithelial-mesenchymal transition by a phosphodiesterase 5 inhibitor via renal klotho expression.

SummaryPhosphodiesterase‐5 (PDE‐5) inhibitors induces vasodilation in several organs by blocking cyclic GMP (guanosine monophosphate) degradation. However, the existence of alternative mechanism of action in case of an impaired nitric oxide (NO) system remains controversial. Previous studies suggested that decreased NO bioavailability may result in the downregulation of klotho expression, but the relationship between klotho and NO remains obscure. Therefore, we investigated whether a PDE‐5 inhibitor could preserve epithelial–mesenchymal transition (EMT) and relationship exists between the NO and renal klotho expression. Ten‐week‐old SD rats (N = 24, 200 g, male) were divided (N = 6) into four groups, which received: A LSD, L‐NAME 1 mg/mL in drinking water, Udenafil 5 mg/kg subcutaneously and both for 4 weeks. Urine nitrate/nitrite, NGAL (Neutrophil gelatinase‐associated lipocalin), and cGMP were measured using ELISA. Kidney was subjected to evaluate PCNA (proliferative cell nuclear antigen), α‐SMA (smooth muscle cell antigen), E‐cadherin, and klotho expression. Urine cGMP decreased after treatment of PDE‐5 inhibitor compared with control due to blocking degradation of cGMP (P < .05, control vs Udenafil and L‐NAME with Udenafil groups). Urine NGAL increased after treating of L‐NAME and attenuated after using PDE‐5 inhibitor (P < .05, control vs L‐NAME and L‐NAME with Udenafil). PCNA, α‐SMA, and E‐cadherin (EMT markers) increased after L‐NAME treatment and normalized after using PDE‐5 inhibitor. Klotho expression showed trend to increase in the L‐NAME with PDE‐5 inhibitor group compared with the L‐NAME group, however, eNOS expression did not change after treatment of L‐NAME or PDE‐5 inhibitor compared with control. PDE‐5 inhibitor alleviates EMT in the kidney via klotho modulation independent of the NO system.

The renoprotective effects of mannitol and udenafil in renal ischemia-reperfusion injury model

PurposeThe aim of this study was to investigate and compare the effects of udenafil and mannitol in an experimental renal ischemia-reperfusion (I/R) injury model.Materials and MethodsA total of 64 female Wister Albino rats were used. Right nephrectomy was performed in all groups. In the control group; I/R injury was not performed. In the I/R group; left renal pedicle was clamped for 45 minutes and then underwent 60 minutes and 24 hours of reperfusion. In the mannitol group; 1 mL 20% mannitol was given intravenously 15 minutes before clamping. In the udenafil group; 10-mg/kg udenafil was given orally 1 hour before clamping. Creatinine (Cr), blood urea nitrogen (BUN), Cr clearance, malondialdehyde, neutrophil gelatinase associated lipocalin (NGAL), histological examination and DNA damage (Comet Assay method) levels were compared in tissue, serum and urine samples.ResultsUdenafil had a better protective effect than mannitol according to biochemical parameters (Cr, BUN, Cr clearance, and NGAL levels) and histopathological findings when compared with the I/R group. In the Comet sampling analysis no significant difference was detected.ConclusionsUdenafil has a better renoprotective effect than mannitol against I/R injury and this effect supports more functional improvements. Further clinical trials are needed to demonstrate those effects and clinical utility of udenafil for that purpose in humans.

Therapeutic effects of udenafil on pressure-overload cardiac hypertrophy.

This study was performed to determine whether the newly developed phosphodiesterase type 5 (PDE5) inhibitor udenafil had beneficial effects on pressure-overload cardiac hypertrophy. Pressure overload cardiac hypertrophy was created by using suprarenal aortic constriction (SAC) in male Sprague-Dawley rats. Rats were divided into three groups: sham (n=19), SAC (n=18) and SAC+udenafil (n=14) groups. Three-week periods of SAC provoked significant left ventricular (LV) hypertrophy. Udenafil was administered (20 mg kg(-1) PO, daily) between the 3rd and 20th weeks after SAC in the SAC+udenafil group. Udenafil improved the survival rate (log-rank P=0.012) and exercise capacity (maximal exercise duration at the 20th week after surgery: 448±54 s for the SAC+udenafil group versus 317±73 s for the SAC group, P<0.05) of the rats with SAC. Serial echocardiographic examinations showed that udenafil attenuated LV remodeling processes following SAC (mean LV end-diastolic dimension at the 20th week after surgery: 9.84±0.59 mm for SAC and 9.05±0.58 mm for SAC+udenafil group, P<0.05). Invasive hemodynamic studies showed that udenafil improved the LV performance. Udenafil-attenuated myocardial fibrosis and apoptosis. Udenafil also decreased myocardial matrix metalloproteinase-9 expression and augmented serum interleukin-10 concentration. Long-term udenafil use prevented cardiac remodeling and improved exercise capacity and survival in rats exposed to pressure-overload cardiac hypertrophy.

PDE 5 inhibition with udenafil improves left ventricular systolic/diastolic functions and exercise capacity in patients with chronic heart failure with reduced ejection fraction; A 12-week, randomized, double-blind, placebo-controlled trial

Impaired nitric oxide-mediated pulmonary vascular tone is commonly found in heart failure with reduced ejection fraction (HFrEF), and is associated with derangement of left ventricular (LV) hemodynamics and decreased exercise capacity, which may be reversed by PDE5 inhibitor. This study investigated the effects of a new, long-acting PDE5 inhibitor on LV hemodynamics and exercise capacity in HFrEF. Patients with chronic HFrEF on optimal medical therapy for >30 days before enrollment were randomly assigned to placebo or udenafil at a dose of 50mg 2x/day for the first 4 weeks followed by 100mg 2x/day for the next 8 weeks. All patients underwent cardiopulmonary exercise echocardiography before and after the 12-week treatment. Improvement of subjective functional capacity was more frequently reported in the udenafil group (P = 0.002). Also, a higher increase in peak VO2 (Δpeak VO2, 21.6% (6.9 ~ 106.4%) vs 1.9% (-15.7 ~ 21.0%) in the placebo group, P = 0.04) and a larger decrease in ventilatory efficiency were observed in the udenafil group (Δ-6.4 ± 9.7 vs Δ1.9 ± 12.1 in the placebo group, P = 0.03). Regarding LV systolic function, the extent of increment in LV ejection fraction was significantly greater in the udenafil group (6.6 ± 6.4% vs 2.3 ± 4.8% in the placebo group, P = 0.02). In the udenafil group, an echocardiographic surrogate of LV filling pressure was more prominently decreased (P = 0.006) along with a significant reverse remodeling of left atrial volume index (57 ± 25mL at baseline to 44 ± 23 at 12th week, P = 0.04) and a progressive fall in B-type natriuretic peptide level (589 ± 679pg/mL at baseline to 220 ± 225pg/mL at 12th week, P < 0.001), indicating LV diastolic function improvement. Udenafil was well tolerated without excess of adverse events compared to placebo. Udenafil improves LV systolic/diastolic functions and exercise capacity in conjunction with established conventional pharmacotherapy, without significant adverse events in HFrEF.

Efficacy and safety of udenafil for the treatment of erectile dysfunction after total mesorectal excision of rectal cancer: A randomized, double-blind, placebo-controlled trial

Nerve-preserving surgery has been provided for patients with rectal cancer; however, sexual dysfunction remains a common complication of rectal cancer surgery. This study explored the efficacy of udenafil to treat erectile dysfunction in male patients who underwent total mesorectal excision (TME) for rectal cancer. We conducted a randomized, double-blind, placebo-controlled clinical trial involving 80 male patients who had decreased International Index of Erectile Function-5 (IIEF-5) scores after TME for rectal cancer. Patients received placebo (50 mg) or udenafil (50 mg) for 12 weeks. The primary outcome variable was the change in IIEF-5 scores. The secondary outcome variables were Sexual Encounter Profile (SEP) questions 2 (Q2) and 3 (Q3), and the Global Assessment Question (GAQ). Baseline IIEF-5 scores, SEP Q2 and Q3 responses, and spontaneous erection rates were consistent in both groups. At the end of treatment, the change in IIEF-5 scores from the baseline was significantly higher in the udenafil group than it was in the placebo group (mean IIEF-5 score, 4.8 ± 4.0 vs 2.0 ± 1.7; P < .05). Responses to SEP Q2, SEP Q3, and GAQ were significantly higher in the udenafil group than they were in the placebo group (SEP Q2, P = .025; SEP Q3, P = .044; GAQ, P < .001). Treatment-related adverse events (n = 4) were all mild in severity. Oral udenafil was deemed safe and effective for the treatment of erectile dysfunction in patients who underwent TME for rectal cancer.

Effects of daily low-dose treatment with phosphodiesterase type 5 inhibitor on cognition, depression, somatization and erectile function in patients with erectile dysfunction: a double-blind, placebo-controlled study

Phosphodiesterase type 5 (PDE5) inhibitors have recently been shown to have cognitive-enhancing effects in animal models and in our previous pilot study. To investigate the efficacy of daily low-dose treatment with a PDE5 inhibitor on cognitive function, depression and somatization in patients with erectile dysfunction (ED), 8-week, double-blind, placebo-controlled study enrolled 60 male patients with ED for ≥ 3 months without cognitive impairment. Forty-nine patients completed the study. Patients were randomized to receive either daily low-dose udenafil 50 mg or placebo for 2 months. The International Index of Erectile Function-5 (IIEF-5), the Korean version of the Mini-Mental State Examination (K-MMSE) for general cognitive function and the Seoul Neuropsychological Screening Battery for comprehensive neuropsychological examination, the Physical Health Questionnaire-9 (PHQ-9) for depression and the Physical Health Questionnaire-15 (PHQ-15) for somatization were administered at baseline and at 2 months. The change in the mean IIEF-5 was significantly higher in the udenafil group than the placebo group (6.08 ± 4.72 vs 2.20 ± 3.50, P=0.008). The changes in the PHQ-9 and PHQ-15 were -2.04 ± 3.14 and -2.17 ± 2.87 in the udenafil group, and 1.20 ± 1.63 and 0.56 ± 2.48 in the placebo group (both, P<0.001). The changes in the K-MMSE and Digit Span Forward were 1.25 ± 1.26 and 0.92 ± 1.02 in the udenafil group, and -0.52 ± 1.19 and -0.24 ± 1.13 in the placebo group (both, P<0.001). However, there were no differences in the other neuropsychological tests. Daily dosing with a PDE5 inhibitor seems to improve cognitive function, depression and somatization, as well as erectile function, in patients with ED.

Combined Therapeutic Effect of Udenafil and Adipose-derived Stem Cell (ADSC)/Brain-derived Neurotrophic Factor (BDNF)–Membrane System in a Rat Model of Cavernous Nerve Injury

To prevent cavernous nerve injury and corpus cavernosum apoptosis-induced erectile dysfunction (ED) after prostatectomy surgery, we investigated whether oral administration of udenafil combination with covering adipose-derived stem cells (ADSCs) and brain-derived neurotrophic factor (BDNF) immobilized poly-lactic-co-glycolic (PLGA) membrane on the injured cavernous nerve could further improve erectile dysfunction. Adult Sprague-Dawley rats were divided into 5 groups: normal group (sham-operated group), bilateral cavernous nerve injury (BCNI) group (BCNI group), udenafil group (oral administration of udenafil 20 mg/kg daily), AB group (BCNI group with ADSCs covered with BDNF membrane on cavernous nerve), AB/udenafil group (AB group with udenafil group). After 4 weeks, erectile function was examined before tissue harvest. Penile tissues were evaluated in terms of the expression of smooth muscle actin (SMA), neuronal nitric oxide synthase (nNOS), and vascular endothelial growth factor (VEGF). The cyclic guanosine monophosphate (cGMP) level of the corpus cavernosum was quantified by cGMP assay. AB/udenafil treatment markedly improved erectile function and prevented the architecture damage of the corpus cavernosum, compared with other treated groups. Udenafil had no statistical significance on increasing nNOS expression, but enhanced VEGF expression. On the contrary, the AB group had no statistical significance on enhancing VEGF expression, but increased nNOS expression. AB/udenafil treatment significantly increased nNOS expression, VEGF expression, and elevated cGMP level, compared with the udenafil group and AB group. The orally administered udenafil combination with ADSC/BDNF-membrane system protected cavernous nerve and improved angiogenesis in the corpus cavernosum, which further maintained erectile function in a rat model of postprostatectomy erectile dysfunction.

Efficacy and Safety of Udenafil for Erectile Dysfunction: A Meta-analysis of Randomized Controlled Trials

To systematically review the evidence on the efficacy and safety of udenafil as treatment of erectile dysfunction from randomized controlled trials. We searched PubMed, Embase, and the Cochrane Library database up to October 2011. The outcome measures assessed were the change from baseline for the International Index of Erectile Function erectile function domain score (primary), the change from baseline for Sexual Encounter Profile questions 2 and 3, the shift to normal rate (erectile function domain ≥ 26), the response to the Global Assessment Questionnaire and adverse effects (secondary). Two of us independently assessed the study quality and extracted data. All data were analyzed using Review Manager, version 5.0.2. Five randomized controlled trials totaling 1109 patients were included. At the follow-up endpoints, udenafil was found to be more effective than placebo, and the tolerability was good. The pooled results showed that the udenafil group was significantly greater than the placebo group in the change from baseline for the International Index of Erectile Function erectile function domain score (mean difference 5.65, 95% confidence interval 4.41-6.89, P < .00001). All included studies indicated that most adverse events were mild or moderate in severity, and no serious adverse events were reported during the study period. The most common drug-related adverse events were flushing and headache (udenafil vs placebo, 5.6% vs 1.8% and 3.1% vs 0%, respectively). The results from the current meta-analysis have suggested that udenafil is an effective and well-tolerated therapy for erectile dysfunction. The findings of the present review highlight the need for more efficient performance of higher quality, large-sample, various-race, long-term, randomized controlled trials to verify the efficacy and safety of udenafil.

Effects of a cGMP-Specific Phosphodiesterase Inhibitor on Expression of Endothelial Nitric Oxide Synthase and Vascular Endothelial Growth Factor in Rats with Cyclosporine-Induced Nephrotoxicity

Background The mechanism of cyclosporine (CsA)–induced nephrotoxicity has been suggested to be vasoconstriction due to reduced nitric oxide (NO), providing tissue fibrosis by elevation of transforming growth factor beta and vascular endothelial growth factor (VEGF). In this study using a rat model of CsA-induced nephrotoxicity, we administered a phosphodiesterase-5 inhibitor to ameliorate the renal injury and alter the expression of endothelial No synthase (eNOS) and VEGF. Methods A right nephrectomy was performed in Sprague-Dawley rats (n = 30; 200–250 g, all male). The Ischemia group (n = 6) underwent ligation of the left renal artery for 45 minutes (IR) before observation for 28 days. After IR, the udenafil group (n = 6) was treated with 10 mg/kg drug orally, the CsA group (n = 6) received 15 mg/kg CsA injected subcutaneously and the CsA plus udenafil group (n = 6) received 15 mg/kg CsA injected subcutaneously together with the oral administration of 10 mg/kg udenafil. Results Administration of udenafil significantly decreased serum creatinine either alone (0.21 ± 0.04 mg/dL) or in combination with CsA (1.86 ± 0.35 mg/dL) versus the ischemia (0.85 ± 0.22 mg/dL) and the CsA alone (3. 10 ± 0.77 mg/dL) group. ( P = .002; P = .002). Comparing the Hematoxylin-eosin staining of the ischemia (0.41 ± 0.09) and CsA (0.44 ± 0.08) groups showed a significantly decreased loss of nuclei in proximal tubules after the administration of udenafil (0.27 ± 0.05 [ P = .004] and 0.26 ± 0.02 [ P = .002] respectively). Immunohistochemical staining showed strong eNOS staining in the udenafil and CsA plus udenafil groups. Western blots for eNOS showed decreased expression in the CsA group and increased expression in the udenafil group. Western blots for VEGF revealed reduced expression only in the CsA plus udenafil group. eNOS mRNA was decreased in the CsA (0.017 ± 0.010) compared with the ischemia group (0.048 ± 0.015; P = .000). VEGF mRNA which was decreased in the CsA group (2.026 ± 1.109), showed greater tendency after administration of udenafil (0.440 ± 0.449) ( P = .003). Conclusion The phosphodiesterase inhibitor ameliorated renal injury in a rat model of CsA-induced nephrotoxicity, possibly related to increased eNOS and reduced VEGF expression.

Efficacy of Udenafil for the Treatment of Erectile Dysfunction up to 12 Hours after Dosing: A Randomized Placebo-Controlled Trial

Udenafil is a newly developed selective phosphodiesterase type 5 inhibitor for the treatment of men with erectile dysfunction (ED). To evaluate the efficacy of udenafil in treating ED for up to 12 hours after dosing. This was a randomized, double-blind, placebo-controlled, parallel-group, fixed dose design, multicenter study. Following a 4-week nondrug baseline period, 104 men with ED of broad etiology and severity were randomized to one of two treatment groups: udenafil 100 mg or placebo. Participants were requested to attempt sexual intercourse at 12 hours after udenafil or placebo dosing during a 4-week treatment period. The primary efficacy variable was the response of patients to question 3 of the Sexual Encounter Profile (SEP Q3). The secondary efficacy measures were the response of patients to question 2 of the Sexual Encounter Profile (SEP Q2). Additional secondary efficacy measures included changes from baseline in the erectile function (EF) domain scores of the International Index of Erectile Function (IIEF) questionnaire. Of the 104 patients, 103 (50 in the udenafil group, 53 in the placebo group) completed the study. Udenafil significantly enhanced the rate of maintenance of erection (SEP Q3; placebo, 28.3% vs. udenafil, 54.7%; P < 0.0001). Significant change from baseline in the IIEF-EF domain was observed in the udenafil group (placebo, -0.58 ± 0.67; udenafil, 4.40 ± 0.84; P < 0.0001). For SEP Q2, there was no difference from baseline and no difference between the two groups. The overall adverse events rate was 11.3%. Most adverse events were mild or moderate in severity, and no serious adverse events were reported during the study and the follow-up period. Udenafil at 100 mg was effective for relieving ED for up to 12 hours after dosing. This duration of effectiveness could allow for flexibility and spontaneity in the sexual lives of patients.

ORIGINAL RESEARCH—ED PHARMACOTHERAPY: The Efficacy and Safety of Udenafil [Zydena] for the Treatment of Erectile Dysfunction in Hypertensive Men Taking Concomitant Antihypertensive Agents

Erectile dysfunction (ED) and hypertension are frequent comorbid conditions. The vasodilating properties of type 5 phosphodiesterase inhibitor (PDE5I) are the major concerns for the treatment of ED patients on antihypertensive medications. To evaluate the efficacy and safety of Udenafil [Zydena] (Dong-A, Seoul, Korea), a newly developed PDE5I, for the treatment of ED patients on antihypertensive medication. It was a multicentered, randomized, double-blind, placebo-controlled, fix-dosed clinical trial among 165 ED patients receiving antihypertensive medications. The subjects treated with placebo, 100 mg or 200 mg of Udenafil for 12 weeks were asked to complete the Sexual Encounter Profile (SEP) diary, the International Index of Erectile Function (IIEF), and the Global Assessment Question (GAQ) during the study period. Primary parameter: the change from baseline for IIEF erectile function domain (EFD) score; Secondary parameters: the IIEF Question 3 and 4, SEP Question 2 and 3, the rate of achieving normal erectile function (EFD > or = 26) and the response to GAQ. Compared to placebo, patients receiving both doses of Udenafil showed significantly improved the IIEF-EFD score. The least squares means for the change from baseline in IIEF-EFD scores were 8.4 and 9.8 for 100 mg and 200 mg Udenafil groups, respectively; those values were significantly higher than that of placebo (2.4, P < 0.0001). Similar results were observed in the comparison of Q3 and Q4 of IIEF, SEP diary and GAQ. Headache and flushing were the most common treatment-emergent adverse events, which were transient and mild-to-moderate in nature. No parameters of efficacy and safety were affected among the subsets stratified according to either the number of antihypertensive medication received or the previous experience of PDE5Is treatment. Udenafil significantly improved erectile function among ED patients with hypertensive symptom treated with concomitant antihypertensive medication. The treatment did not increase the frequency or severity of adverse events.