mirodenafil and Hypertension

Mirodenafil is a recently developed oral phosphodiesterase type 5 inhibitor, which was observed to significantly improve erectile function and was well tolerated in men with broad-spectrum erectile dysfunction (ED).. To investigate the efficacy and safety of mirodenafil treatment compared with placebo in men taking at least one antihypertensive medication.. A multicenter, double-blind, placebo-controlled, parallel group, fixed-dose study was conducted with 109 subjects who were randomized to placebo or mirodenafil 100 mg for 12 weeks on an "as needed" basis.. The primary efficacy measures were the changes from baseline in sum of scores on International Index of Erectile Function-erectile function domain (IIEF-EF) questions 1 to 5 and 15 with treatment. The secondary efficacy measures included scores on IIEF question 3 and 4 (Q3 and Q4), all domain scores of IIEF, and Sexual Encounter Profile Question 2 and 3 (SEP2 and SEP3) along with responses to Global Assessment Question (GAQ) and Life Satisfaction Checklist (LSC). The safety assessments included laboratory tests, vital signs, 12-lead electrocardiogram recordings, and patients' reporting of adverse events.. The mirodenafil group showed significantly greater increase in IIEF-EF scores at 12 weeks compared with the placebo group (9.35 ± 6.86 vs. 2.66 ± 6.44, P<0.001). The mirodenafil group also demonstrated significantly greater improvement in scores of IIEF Q3 and Q4, other four domains of IIEF, SEP2, SEP3, and LSC along with percentages of patients responding positively to GAQ compared with the placebo group. During the study, no clinically significant changes were observed regarding blood pressure, heart rate, electrocardiographic findings, or laboratory values. Facial flushing and headache were the most common treatment-associated adverse events, which were mild or moderate in severity, resolving spontaneously.. Mirodenafil was effective and safe in men with ED concomitantly taking antihypertensive medications.

Topics: Antihypertensive Agents; Blood Pressure; Double-Blind Method; Electrocardiography; Erectile Dysfunction; Flushing; Headache; Heart Rate; Humans; Hypertension; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Pyrimidinones; Sulfonamides

Hypertension is the most common comorbidity and major risk factor in patients with erectile dysfunction. The pharmacokinetics of mirodenafil, used for the treatment of erectile dysfunction, after the intravenous and oral administration (20 mg/kg) to 6-week-old rats (with blood pressure within the normotensive range) and 16-week-old spontaneously hypertensive rats (SHRs) and their age-matched control normotensive Kyoto-Wistar (KW) rats, and 16-week-old deoxycorticosterone acetate-salt-induced hypertensive rats (DOCA-salt rats) and their age-matched control Sprague-Dawley (SD) rats were compared. It was found that time-averaged renal clearance (Cl(r)) was of minor importance and that time-averaged non-renal clearance (Cl(nr)) was dominant. In both 6- and 16-week-old SHRs, the Cl(nr)s and areas under the curve (AUCs) of intravenous mirodenafil were significantly smaller and greater than those of the controls, but in 16-week-old DOCA-salt rats, they were comparable to the controls. Although the AUC of oral mirodenafil in 16-week-old SHRs was comparable to the controls, the Cl(nr)s (or total body clearances, Cls) of intravenous mirodenafil and intestinal intrinsic clearances were significantly smaller than the controls and comparable to the controls for both 6- and 16-week-old SHRs, unlike in the 16-week-old DOCA-salt rats. The above data suggest that the significantly smaller Cl(nr) and greater AUC of intravenous mirodenafil and comparable AUC of oral mirodenafil in 16-week-old SHR could be due to the hereditary characteristics of SHRs, and not due to the hypertensive state itself.

Topics: Animals; Desoxycorticosterone; Disease Models, Animal; Hypertension; Male; Pyrimidinones; Random Allocation; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Sprague-Dawley; Sulfonamides