Material and Methods We reviewed the following databases to
Material and Methods
We reviewed the following databases to obtain relevant studies of udenafil: PubMed, Embase, and the Cochrane Library. The following search terms were used: (“udenafil” OR “Zydena” OR “DA 8159”) AND (“Erectile Dysfunction” OR “Impotence”). We also searched the references of included studies to identify additional potentially relevant studies. Only 1 randomized controlled trial was identified in which patients were randomized to receive either udenafil or placebo for ED. No language restrictions were used. The titles and abstracts were screened independently by 2 reviewers, who discarded the studies that 5,7-dihydroxychromone synthesis were not applicable, and 2 reviewers independently assessed the retrieved titles and abstracts of all identified trials to confirm fulfillment of the inclusion criteria. Data extraction was performed independently by the same investigators using standard data extraction forms. To reduce bias, 1 of the reviewers was unaware of the source of the publication and the authors\' names. Disagreements were resolved in consultation with the third reviewers. The quality of the included randomized trials was assessed using the Cochrane Collaboration tool.
Results The combined search strategies identified 5 randomized controlled trials, including 1109 patients (561 in the udenafil group and 548 in the placebo group), that met the inclusion criteria (Fig. 1). All studies11, 12, 13, 14, 15 were multicenter, double-blind, randomized, placebo-controlled, parallel-group study and came from Korea. Three studies13, 14, 15 used 100 and 200 mg udenafil; one study used 100 mg udenafil; one study used 25, 50, and 75 mg udenafil. The study duration ranged from 4 to 12 weeks. Three studies reported the change from baseline for the IIEF EFD score, the change from baseline for SEP questions 2 and 3, the shift to a normal rate (EFD ≥26), and the response to the GAQ. One study reported the change from baseline for the IIEF EFD score, the change from baseline for SEP questions 2 and 3, and the shift to a normal rate (EFD ≥26). Another study reported the IIEF EFD score, the change from baseline for SEP questions 2 and 3, and the response to the GAQ. The characteristics and quality assessment of the 5 studies are summarized in Table 1, Table 2. Compared with placebo, the results of the meta-analysis for the efficacy of udenafil for ED are summarized in Table 3.
Comment To our knowledge, this is first meta-analysis to evaluate the efficacy and safety of udenafil for ED. As a new oral PDE5-I, udenafil is a pyrazolopyrimidinone derivative with a molecular weight of 516.66. In the Phase I and II study, the results demonstrated that udenafil was efficacious in 55% of patients with ED 8-12 hours after administration, and udenafil treatment produced a highly significant improvement in ejection fraction, with up to a 91% vaginal penetration success rate. Our pooled results demonstrated that udenafil can significantly improve the ED of patients, including the IIEF erectile function domain score, SEP questions 2 and 3, the shift to normal rate (EFD ≥26), and the response to the GAQ, with no serious adverse events during the study period. The most common drug-related adverse events were flushing and headache compared with placebo. Nonadrenergic-noncholinergic nerves in the penis release NO and acetylcholine, which stimulate relaxation of the corpus cavernosum smooth muscle and produce erections. NO is an important regulator of cavernosal smooth muscle relaxation. NO also induces arterial dilation. NO diffuses to smooth muscle cells, where it augments the formation of cGMP, which acts as a second messenger. At this point, the NO/cGMP/cGMP-dependent protein kinase I pathway serves as the principal regulatory basis for penile erection. This pathway offers multiple molecular sites for pharmacologic targeting, including catalytic enzymes, biochemical cofactors and products, and degradative enzymes. The enzyme PDE5 is a selective inactivator of cGMP in the cavernosal smooth muscle.18, 19, 20 Most well known are the commercially available, orally effective PDE5-Is, such as sildenafil, vardenafil, and tadalafil. Similarly, udenafil as a PDE5-I treats ED in the same manner.