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.