In the United States, most men who use PDE5 inhibitors (i.e., avanafil, sildenafil, tadalafil, vardenafil) for restoration of sexual function use them on a PRN basis. One of the reasons for PRN use is that the short half-life of all currently FDA-approved PDE5 inhibitors, except tadalafil, is too short to provide sustained 24-hour enhancement of cyclic GMP, the chemical messenger responsible for corpora cavernosa vascular dilation. Because of its 18-hour half-life, tadalafil is well suited to low-dose daily administration, but the time to onset of efficacy may be somewhat slower than the other PDE5 inhibitors.
In Korea, another PDE5 inhibitor — udenafil — is approved for the treatment of erectile dysfunction (ED). Similar to tadalafil, udenafil has a long half-life (11-13 hours), making it suitable for once-daily administration. In contrast to tadalafil, it has a more rapid onset of action (time to maximum plasma concentration = 0.8-1.3 hours) than tadalafil (2 hours). Shim et al performed a 2-month, placebo-controlled trial of once-daily udenafil among men (n = 49) with ED. The outcomes included not only erectile function but also assessments of depression (PHQ-9), somatization (PHQ-15), and cognitive function (Korean MMSE and Seoul Neuropsychological Screening Battery).
As has been shown with other PDE5 inhibitors, there was a substantial improvement in erectile function. In addition, treatment with udenafil improved measurements of cognition, depression, and somatization compared to placebo. Improved erectile function has previously been shown to improve depression and quality of life, but Shim et al suggest that there may also be direct central nervous system, vascular, and nitrergic pathways that could lead to the outcomes improvement they detected.
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