Safety, tolerability and pharmacokinetics of udenafil, a novel PDE‐5 inhibitor, in healthy young Korean subjects

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The phosphodiesterase (PDE) type 5 inhibitor is a widely used agent that facilitates penile erection. • Udenafil is newly developed as a PDE‐5 inhibitor. WHAT THIS STUDY ADDS • This is the first study to determine the safety, tolerability and pharmacokinetics of udenafil in healthy subjects. • Udenafil was safe and well tolerated in healthy Korean subjects. • The AUC and Cmax of udenafil increased supraproportionally with increasing dose upon single administration, but there was no significant drug accumulation upon multiple administrations. AIM To evaluate the safety, tolerability and pharmacokinetics (PK) of udenafil, a novel phosphodiesterase type 5 inhibitor. METHODS A double‐blind, randomized, placebo‐controlled, dose‐rising, parallel‐group, single‐ and multiple‐dose study was conducted in healthy Korean subjects. The subjects were allocated to single‐dose groups of 25, 50, 100, 200 or 300 mg (eight subjects in each dose group, including two placebos), or to multiple‐dose groups of 100 or 200 mg (once‐daily dosing for 7 days; nine subjects in each dose group, including three placebos). Serial samples of blood and urine were collected after oral administration and the drug concentrations in plasma and urine were determined by high‐performance liquid chromatography. Safety and tolerability were evaluated by monitoring clinical laboratory parameters and adverse events. RESULTS Udenafil reached peak plasma concentrations at 0.8–1.3 h, and then declined mono‐exponentially with a terminal half‐life of 7.3–12.1 h in the single‐dose study. The area under the time–concentration curves (AUC) and maximum plasma concentrations (Cmax) increased supraproportionally with increasing dose in the single‐dose study. During multiple dosing, a steady state was reached at 5 days and little accumulation occurred after repeated dosing for 7 days. Udenafil was generally well tolerated in these healthy subjects, and no serious adverse events occurred. CONCLUSIONS Udenafil was safe and well tolerated in healthy volunteers. The AUC and Cmax of udenafil increased supraproportionally with increasing dose upon single administration, but there was no significant drug accumulation upon multiple administrations.

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

“…Udenafil is metabolized by CYP3A4, and the systemic exposure of the drug increased significantly when it was administered together with ketoconazole (Shin et al, 2010). In a broad population of Korean men with ED, Paick et al (2008) showed that udenafil was effective. The effect of a 100-mg dose had a duration of at least 12 h (Park et al, 2010b).…”

Safety and efficacy of the simultaneous administration of udenafil and an α-blocker in men with erectile dysfunction concomitant with BPH/LUTS

“…The efficacy and safety of udenafil have been shown to be similar to those of the other PDE-5 inhibitors. 10,15,28 Although udenafil is one of the most popular agents for treating ED in Korea, it is not yet available outside Korea, although phase IIa and III trials have been conducted in the United States since 2006. This is the first report showing that udenafil has similar safety and efficacy to other PDE-5 inhibitors when coadministered with a-blockers.…”

“…The incidence of adverse events was similar to earlier reports on monotherapy using PDE-5 inhibitors in patients with ED, or with monotherapy using a-blockers in patients with BPH/LUTS. 8,28,[30][31][32] Thus, the coadministration of udenafil and a-blockers did not elevate the incidence of such adverse events, so the therapy appears safe.…”

Use of udenafil is not associated with a reduction in post-ERCP pancreatitis: results of a randomized, placebo-controlled, multicenter trial

“…Udenafil (100 mg) reaches maximal plasma concentration within 2 hours and produces time of onset within 1 hour, similar to other PDE-5 inhibitors at equivalent doses, including sildenafil (50 mg) and vardenafil (10 mg). 32,33 Based on this pharmacokinetics, udenafil 100 mg was given 2 hours before ERCP so that maximal plasma concentration was achieved and the anticipated effect on the SO had begun to take place. In patients with suspected SOD, vardenafil 10 mg significantly decreased SO tone.…”