J Clin Pharmacol. 2018 Jul;58(7):905-912. doi: 10.1002/jcph.1095. Epub 2018 Mar 14.

Effects of Renal Impairment on the Pharmacokinetics and Safety of Udenafil.

Cho YS, Noh YH, Lim HS, Cho SH, Ghim JL, Choe S, Kim SB, Park JS, Lee SK, Yang WS, Chang JW, Bahng MY, Bae KS.

Abstract

Udenafil is a phosphodiesterase-5 inhibitor used to treat erectile dysfunction. Although udenafil is not predominantly eliminated by the kidney, renal impairment can alter its secretion/transport pathways. Drug pharmacokinetics and safety must therefore be assessed in subjects with a renal impairment. We investigated the effects of impaired renal function on the pharmacokinetics  and safety of a single 100-mg oral dose of udenafil in a single-dose, open-label, parallel-group study of 31 subjects. Cockcroft-Gault creatinine clearance was used to stratify these subjects into healthy controls (>80 mL·min-1 ) and individuals with mild (50 to ≤80 mL·min-1 ), moderate (30 to ≤50 mL·min-1 ), and severe (<30 mL·min-1 ) renal impairment. Pharmacokinetic measurements and safety assessments indicated that the geometric mean of the area under the concentration-time curve to the last measurement in mildly, moderately, and severely renally impaired subjects was 1.30- (90% CI 1.05-1.60), 1.62- (90% CI 1.28-2.06), and 1.60- (90% CI 1.28-2.01) fold higher, respectively, than the healthy controls. The geometric mean of the maximum observed concentration was 1.41- (90% CI 1.05-1.88), 2.02- (90% CI 1.47-2.79), and 1.65- (90% CI: 1.21-2.24) fold higher, respectively. Significant correlations were observed among the creatinine clearance, oral clearance, and maximum concentration of udenafil (P < .01). All adverse events were mild, and no subject discontinued the study. Udenafil administration was well tolerated in all groups. In view of the clinical relevance of drug exposure, our findings indicate that a dose adjustment of udenafil is warranted in subjects with moderate or severe renal impairment.

KEYWORDS: Pharmacokinetics; Phosphodiesterase-5; Renal impairment; Safety; Udenafil

PMID:

29537612 

DOI:

10.1002/jcph.1095