The phosphodiesterase-5-inhibitor udenafil lowers portal pressure in compensated preascitic liver cirrhosis. A dose-finding phase-II-study.

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 12.5mg/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.