The phosphodiesterase-5-inhibitor udenafil lowers portal pressure in compensated preascitic liver cirrhosis. A dose-finding phase-II-study. Issue 2 (February 2015)

• Record Type: Journal Article
• Authors: Kreisel, Wolfgang; Deibert, Peter; Kupcinskas, Limas; Sumskiene, Jolanta; Appenrodt, Beate; Roth, Susanne; Neagu, Michaela; Rössle, Martin; Zipprich, Alexander; Caca, Karel; Ferlitsch, Arnulf; Dilger, Karin; Mohrbacher, Ralf; Greinwald, Roland; Sauerbruch, Tilman
• Is Part Of: Digestive and liver disease. Volume 47:Issue 2(2015)
• Page Start: 144
• Page End: 150
• Publication Date: 2015-02
• Subjects: Liver cirrhosis -- Phosphodiesterase-5-inhibitors -- Portal hypertension -- Portal pressure -- Udenafil; Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; 616.33005
• DOI: 10.1016/j.dld.2014.10.018
• Languages: English
• ISSNs: 1590-8658

Abstract

Abstract: Background: Phosphodiesterase-5-inhibitors may lower portal pressure. Aims: To investigate the effect of the phosphodiesterase-5-inhibitor udenafil on hepatic and systemic haemodynamics in liver cirrhosis. Methods: In an open-label phase-II-study, patients with liver cirrhosis Child A/B and hepatic venous pressure-gradient ≥12 mmHg received 12.5 mg/day, 25 mg/day, 50 mg/day, 75 mg/day ( n = 5, each), or 100 mg/day ( n = 10) udenafil p.o. for one week. On days 0 and 6, hepatic venous pressure-gradient was measured prior to and one hour after drug ingestion. Endpoints were reduction of hepatic venous pressure-gradient from day 0 pre to day 6 post intake and reduction in the acute setting. Pharmacokinetics were measured in the two lowest dosage groups. Results: Combining the 75 and 100 mg/day groups hepatic venous pressure-gradient reduction after drug intake was 19.9% ( p = 0.0006) on day 0. From day 0 pre-dose to day 6 post-dose hepatic venous pressure-gradient decreased by 15.7% ( p = 0.040) and in 5/15 patients by ≥20% or to <12 mmHg. In the 100 mg/day group, mean arterial pressure decreased from 98.9 mmHg by 6.2 mmHg ( p = 0.037) from day 0 pre-dose to day 6 post-dose. Heart rates or electrocardiograms were unchanged. Udenafil was eliminated with t 1/2 = 25 h. Conclusions: Oral application of 75–100 mg of the phosphodiesterase-5-inhibitor udenafil lowers portal pressure in the acute setting by about 20% without relevant systemic cardiovascular side effects.