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 12.5mg/day, 25mg/day, 50mg/day, 75 mg/day (n = 5, each), or 100mg/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 100mg/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 100mg/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 t1/2 = 25 h. CONCLUSIONS: Oral application of 75-100mg of the phosphodiesterase-5-inhibitor udenafil lowers portal pressure in the acute setting by about 20% without relevant systemic cardiovascular side effects.
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 cirrhosisChild A/B and hepatic venous pressure-gradient ≥ 12 mmHg received 12.5mg/day, 25mg/day, 50mg/day, 75 mg/day (n = 5, each), or 100mg/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 100mg/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 100mg/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 t1/2 = 25 h. CONCLUSIONS: Oral application of 75-100mg of the phosphodiesterase-5-inhibitor udenafil lowers portal pressure in the acute setting by about 20% without relevant systemic cardiovascular side effects.
Authors: Ksenia Brusilovskaya; Philipp Königshofer; Daniel Lampach; Adrian Szodl; Paul Supper; David Bauer; Andrea Beer; Judith Stift; Gerald Timelthaler; Georg Oberhuber; Bruno Karl Podesser; Martha Seif; Kerstin Zinober; Nataliya Rohr-Udilova; Michael Trauner; Thomas Reiberger; Philipp Schwabl Journal: United European Gastroenterol J Date: 2020-09-02 Impact factor: 4.623
Authors: Philipp Schwabl; Ksenia Brusilovskaya; Paul Supper; David Bauer; Philipp Königshofer; Florian Riedl; Hubert Hayden; Claudia Daniela Fuchs; Judith Stift; Georg Oberhuber; Stefan Aschauer; Diana Bonderman; Thorsten Gnad; Alexander Pfeifer; Frank Erhard Uschner; Jonel Trebicka; Nataliya Rohr-Udilova; Bruno Karl Podesser; Markus Peck-Radosavljevic; Michael Trauner; Thomas Reiberger Journal: Sci Rep Date: 2018-06-19 Impact factor: 4.379
Authors: Denise Schaffner; Adhara Lazaro; Peter Deibert; Peter Hasselblatt; Patrick Stoll; Lisa Fauth; Manfred W Baumstark; Irmgard Merfort; Annette Schmitt-Graeff; Wolfgang Kreisel Journal: World J Gastroenterol Date: 2018-10-14 Impact factor: 5.742