Udenafil

Population pharmacokinetic analysis to recommend the optimal dose of udenafil in patients with mild and moderate hepatic impairment.[Pubmed:27084997]

Br J Clin Pharmacol. 2016 Aug;82(2):389-98.

AIMS: The aim of this study was to develop a population pharmacokinetic (PK) model of Udenafil and its active metabolite, DA-8164, in healthy subjects and patients with hepatic impairment (HI) and to estimate the optimal dosing recommendations for patients with HI. METHODS: An open label, three parallel group, age and weight matched control study was conducted in 18 volunteers, six healthy subjects (n = 6) and patients with mild (Child-Pugh class A, n = 6) and moderate HI (Child-Pugh class B, n = 6). Serial blood samples were collected for up to 72 h after a single administration of Udenafil 100 mg. A population PK model was developed using non-linear mixed effects modelling (nonmem, ver. 7.2). The simulated data from the final PK model and original data of healthy subjects were compared to identify the optimal dose for patients with HI. RESULTS: A two compartment model for both Udenafil and DA-8164 best described the data. Prothrombin time on metabolic clearance of Udenafil to DA-8164 was included in the final model as a covariate. Compared with the AUC(0,tlast ) value after administration of Udenafil 100 mg to healthy subjects, the geometric mean ratios (95% confidence interval) after 100 mg and 75 mg Udenafil administration were 1.21 (1.10, 1.32) and 0.74 (0.67, 0.81) in patients with mild HI, respectively. Meanwhile, those were 1.55 (1.43, 1.67) and 1.02 (0.92, 1.12) in patients with moderate HI, respectively. CONCLUSIONS: This study suggests that the recommended doses of Udenafil are 100 mg and 75 mg in patients with mild and moderate HI, respectively.

A Phase 3 Study to Evaluate the 1-Year Efficacy and Safety of Udenafil 75 mg Once Daily in Patients With Erectile Dysfunction.[Pubmed:27319276]

J Sex Med. 2016 Aug;13(8):1263-9.

INTRODUCTION: Once-daily administration of phosphodiesterase type 5 inhibitors has been shown to correct erectile dysfunction (ED). AIM: To evaluate the long-term efficacy and safety after once-daily oral administration of Udenafil 75 mg in men with ED. METHODS: This clinical trial was an open-label, fixed-dose, 24-week extension study (DA8159_EDDL_III) of a 24-week double-blinded efficacy and safety study of once-daily Udenafil (parent study: DA8159_EDD_III). Subjects received Udenafil 75 mg once daily for 24 weeks during this extension study, and the follow-up visit occurred during the 4-week ED treatment-free period. MAIN OUTCOME MEASURES: Subjects were asked to complete the International Index of Erectile Function questionnaire and the Global Assessment Questionnaire at the 24-week extension and after the 4-week ED treatment-free period, and the development of adverse drug reactions was investigated. RESULTS: In total, 302 subjects were enrolled in this extension study. Improvement was shown with an increased erectile function (EF) domain score compared with baseline (14.60 +/- 4.57) at extension week 48 (23.98 +/- 5.44) and a slight increase in EF domain score compared with the last time point (week 24) of the parent study (P < .001). The Global Assessment Questionnaire showed a high improvement rate of 95.4% at the extension 48-week time point. For shift to normal, almost half the subjects (45.1%) recovered "normal" EF, and 14.2% of subjects reported normal erections after the 4-week ED treatment-free period. The occurrence rate of adverse drug reactions was 8%, which consisted mainly of flushing and headache. CONCLUSION: Once-daily dosing of Udenafil 75 mg showed excellent efficacy and safety with long-term administration and allowed a more spontaneous sexual life.

The Effect of Age on the Pharmacokinetics of Udenafil in Healthy Subjects.[Pubmed:27006150]

J Clin Pharmacol. 2016 Nov;56(11):1372-1377.

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 mug/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 mug.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.