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

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver

PubMedID: 25483910

Kreisel W, Deibert P, Kupcinskas L, Sumskiene J, Appenrodt B, Roth S, Neagu M, Rössle M, Zipprich A, Caca K, Ferlitsch A, Dilger K, Mohrbacher R, Greinwald R, Sauerbruch T. The phosphodiesterase-5-inhibitor udenafil lowers portal pressure in compensated preascitic liver cirrhosis. A dose-finding phase-II-study. Dig Liver Dis. 2014;.
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 =12mmHg received 12.5mg/day, 25mg/day, 50mg/day, 75mg/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 <12mmHg. In the 100mg/day group, mean arterial pressure decreased from 98.9mmHg by 6.2mmHg (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=25h.

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.