Abstract
The purpose of this study was to investigate the therapeutic efficacy of udenafil (CAS 268203-93-6), a phosphodiesterase type 5 (PDE5) inhibitor, on bile duct ligation (BDL)-induced portal hypertension. Udenafil was given orally to rats at dose levels of 1, 5 or 25 mg/kg/day for 3 weeks in order to examine the chronic effect on portal venous pressure (PVP). Udenafil was also given orally to investigate the sequential change of PVP in BDL animals. The effect of udenafil on hepatic stellate cell activation and fibrotic change-related protein mRNA expression were examined. In a pharmacokinetic study, the pharmacokinetic parameters in sham-operated rats and BDL rats were compared. Three-week udenafil treatment decreased PVP by approximately 30% compared to the vehicle group. In a single oral administration study, the PVP of the udenafil treated group was lower than that of the control group throughout the experimental period. Compared to control, udenafil suppressed the expression of procollagen type I and alpha-smooth muscle actin mRNA. In the pharmacokinetic study, the AUC of udenafil in BDL rats was approximately 5 times higher than that in sham-operated rats. The results of this study suggest that udenafil has beneficial effects on portal hypertension and the effect may well be attributed to its anti-fibrogenic activity.
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