Safety, tolerability and pharmacokinetics of udenafil, a novel PDE-5 inhibitor, in healthy young Korean subjects.
BACKGROUND
The phosphodiesterase (PDE) type 5 inhibitor is a widely used agent that facilitates penile erection. Udenafil is newly developed as a PDE-5 inhibitor.


CONCLUSIONS
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 C(max) of udenafil increased supraproportionally with increasing dose upon single administration, but there was no significant drug accumulation upon multiple administrations.


OBJECTIVE
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 (C(max)) 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 C(max) of udenafil increased supraproportionally with increasing dose upon single administration, but there was no significant drug accumulation upon multiple administrations.
Kim
Bo-Hyung
BH
Departments of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, Seoul, Korea.
Lim
Hyeong-Seok
HS
Chung
Jae-Yong
JY
Kim
Jung-Ryul
JR
Lim
Kyoung Soo
KS
Sohn
Dong-Ryul
DR
Cho
Joo-Youn
JY
Yu
Kyung-Sang
KS
Shin
Sang-Goo
SG
Paick
Jae-Seung
JS
Jang
In-Jin
IJ
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006801:Humans; D007723:Korea; D008297:Male; D010410:Penile Erection / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D013449:Sulfonamides; D000096926:Benzenesulfonamides
D010726:Phosphodiesterase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C419664:udenafil; D000096926:Benzenesulfonamides