title: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: University Hospital Freiburg, Freiburg, Germany. Electronic address: wolfgang.kreisel@uniklinik-freiburg.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kreisel
authors.affiliation: University Hospital Freiburg, Freiburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Deibert
authors.affiliation: Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Limas
authors.initials: L
authors.lastname: Kupcinskas
authors.affiliation: Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Sumskiene
authors.affiliation: University Hospital, Homburg, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Appenrodt
authors.affiliation: University Hospital Freiburg, Freiburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Roth
authors.affiliation: University Hospital Freiburg, Freiburg, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Neagu
authors.affiliation: Gastroenterology Centre, Freiburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Rössle
authors.affiliation: University Hospital, Halle, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zipprich
authors.affiliation: Klinikum Ludwigsburg, Ludwigsburg, Germany.
authors.forename: Karel
authors.initials: K
authors.lastname: Caca
authors.affiliation: Medical University, Wien, Austria.
authors.forename: Arnulf
authors.initials: A
authors.lastname: Ferlitsch
authors.affiliation: Dr. Falk Pharma GmbH, Freiburg, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Dilger
authors.affiliation: Dr. Falk Pharma GmbH, Freiburg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Mohrbacher
authors.affiliation: Dr. Falk Pharma GmbH, Freiburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Greinwald
authors.affiliation: University Hospital, Bonn, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Sauerbruch
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000209:etiology; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome; D000096926:Benzenesulfonamides
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C419664:udenafil; D000096926:Benzenesulfonamides
keywords: Liver cirrhosis; Phosphodiesterase-5-inhibitors; Portal hypertension; Portal pressure; Udenafil