br Results br Discussion The nitric oxide
Discussion The nitric oxide-cyclic guanosine monophosphate pathway plays an important role in normal EF, and oral PDE-5Is were developed in the late 90s after the discovery that ED occurs when there is a problem with this pathway. Since then, several PDF-5Is with different pharmacokinetics and dynamics, including sildenafil, vardenafil, and tadalafil, have been marketed and administered for treatment of ED. Udenafil, with a similar mechanism of action, was also developed later and was marketed in Korea in 2005. In accordance with the development of novel PDE-5Is, modification of the administration strategy was introduced in order to maximize efficacy and patient\'s compliance in the treatment of ED, and long-term repeated administration of PDE-5Is has been suggested as a possibility for suppressing the progression of ED or as a treatment for the cause of ED 2, 11, 12. In particular, tadalafil, with a longer half-life of 17.5 hours, has been reported to show persistent action for up to 36 hours with safe doses of 10 mg and 20 mg, compared with other PDE-5Is, and once-daily administration of 2.5 mg or 5 mg of tadalafil has been reported to show effectiveness and safety for treatment of ED . Because udenafil has a maximum half-life of 12.1 hours, followed by tadalafil, this unique pharmacokinetics may allow clinical efficacy in comparison with initially developed, relatively short-acting PDE-5Is. In a recent study of the pharmacodynamics and mechanisms of udenafil, the half-maximal inhibitory concentration (IC50) for PDE5 of udenafil was similar to that of sildenafil . In a previous study using an animal model in diabetes and hyperlipidemia, once-daily administration of udenafil resulted in maintenance of erection by improving the function of endothelial cells, which was achieved by suppression of the reduction in cavernosal endothelial EG00229 synthesis and smooth muscle content 15, 16. Based on this finding, we conducted a clinical trial on low doses of udenafil (25 mg, 50 mg, and 75 mg) once per day for 3 months, reporting significant improvement of EF for doses of udenafil of 50 and 75 mg, in comparison with placebo . Thereby, udenafil 50 mg once per day was approved for marketing in October 2010, and this study was designed for further evaluation of the safety and efficacy of udenafil 50 mg and udenafil 75 mg for the longer term of 24 weeks. In this trial, the change from baseline of the IIEF-EF domain showed an increase of 7.9 points for udenafil 50 mg and 8.83 points for udenafil 75 mg 6 months after administration of the drug compared with before administration of the drug. These data re-confirmed the therapeutic effects for treatment of ED when udenafil was taken once per day at low doses (50 mg, 75 mg) for 24 weeks, even when compared with the results of an increase of 6.59 points for udenafil 50 mg and 8.34 points for udenafil 75 mg in the previous trial for 12 weeks . One peculiar finding from this study was a slight difference observed between the two dosages of udenafil. In evaluation of the severity of ED according to the baseline IIEF-EF domain score, significant improvement was observed only with udenafil 75 mg, regardless of the severity of baseline ED. In contrast, in patients with mild baseline ED, udenafil 50 mg did not increase IIEF-EF score at both 12 and 24 weeks. In the same context, in this particular group with mild ED, a significant difference in the proportion of patients with return of normal EF was found between the udenafil 50 mg (50%) and 75 mg (100%) group.
Statement of Authorship
Introduction Udenafil is a selective phosphodiesterase type 5 inhibitor (PDE5-I) and an “on-demand” form of oral medication indicated for men with erectile dysfunction (ED). Recent clinical tests have reported that daily dosing of PDE5-I shows some advantage in treatment effect at a comparatively lower dose than on-demand dosing.2, 3, 4, 5 This is theoretically based on the treatment of refractory ED accompanied by conditions such as diabetes, prostatectomy, and spinal injury, achieving a more natural erection, and maintaining consistent sexual function rather than the limited erection induced by the on-demand administration of drugs. In fact, many recent clinical studies have reported that once-daily treatment with PDE5-Is significantly improves erectile function (EF) in men with mild and mild to moderate impairments in EF after on-demand PDE5-I treatment.2, 3, 4, 5 Long-term administration of PDE5-Is inhibits the decrease of vascular endothelial cell function, thus accelerating vascular relaxation, inhibits the decrease in endothelial cell and smooth muscle contents, and prevents their fibrosis within the penile corpus cavernosum.7, 8, 9, 10