Udenafil, a cyclic guanosine monophosphate-specific phosphodiesterase type 5 inhibitor, has been developed to treat erectile dysfunction. We evaluated the effect of age on the pharmacokinetics and tolerability of udenafil. A single-center, open-label, parallel-group phase 1 study was conducted in healthy adult subjects who took a single oral dose of udenafil (100 mg). The pharmacokinetics and tolerability of udenafil were compared between 12 healthy young men (21-27 years) and 12 healthy elderly men (65-78 years). Serial blood and urine samples were collected for up to 60 and 48 hours after dosing. The plasma concentrations of udenafil and its major metabolite, DA-8164, were analyzed using a validated liquid chromatography-tandem mass spectrometry method. The mean Cmax of udenafil tended to be slightly less (214.0 vs 292.8 μg/L) in the elderly compared with the young (GMR, 68.9; 95% CI, 48.9-97.1); however, the AUC did not differ between the groups (1858.8 vs 2100.6 μg·h/L; GMR, 84.6; 95% CI, 66.1-108.4). The mean t1/2 was prolonged by approximately 5 hours in the elderly (P < .05). The clearance and metabolic AUC ratio did not differ between the elderly and young. In terms of tolerability, all adverse events were mild, and all subjects recovered without additional therapy. The systemic exposure of elderly subjects to udenafil appears to be comparable to or slightly less than that of young healthy subjects. Based on our pharmacokinetic comparisons, udenafil dose adjustment is unlikely to be required in the elderly population.
Keywords: PDE5 inhibitor; age effect; erectile dysfunction; pharmacokinetics and drug metabolism; udenafil.
© 2016, The American College of Clinical Pharmacology.