title: Acute haemodynamic response in relation to plasma vardenafil concentrations in patients with pulmonary hypertension.
abstract: OBJECTIVE
  To evaluate the acute haemodynamic effects of a single oral dose of vardenafil and to study the drug concentration in relation to haemodynamic effects in patients with pulmonary hypertension (PH).
  
  
  METHODS
  Sixteen patients with PH (aged 29-85\ years), received one single oral dose of vardenafil (5, 10 or 20 mg). The haemodynamic effect was assessed over a 60 min period. Vardenafil plasma concentrations were measured after 15, 30, 45 and 60 min using liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  At 60 min a reduction in mPAP with a median % decrease of -20.3% (range -48.3 to 3.0; P < 0.001) and an increase in cardiac output and the cardiac index with a median % change of 10.6% (range -25.0 to 88.1; P = 0.015) and 12.1% (range -24.0 to 94.4; P = 0.01) respectively was observed. The pulmonary vascular resistance (PVR) was reduced with a median % decrease of -28.9% (range -61.5 to -5.9; P < 0.001), and pulmonary selectivity was reflected by a median percent reduction of -16.9% (range -49.0 to 16.5; P = 0.002; n = 14) in the PVR/systemic vascular resistance ratio. There was a correlation between the plasma concentrations of vardenafil and change in mPAP (r = -0.579, P = 0.019) and between vardenafil concentrations and change in PVR (r = -0.662, P = 0.005).
  
  
  CONCLUSIONS
  Vardenafil causes rapid changes in cardiopulmonary haemodynamics and there is a correlation between plasma vardenafil drug concentration and the acute changes in mPAP as well as PVR in patients with PH.
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala University Hospital, Uppsala, Sweden. dan_henrohn@hotmail.com
authors.forename: Dan
authors.initials: D
authors.lastname: Henrohn
authors.forename: Anna
authors.initials: A
authors.lastname: Sandqvist
authors.forename: Mikael
authors.initials: M
authors.lastname: Hedeland
authors.forename: Hanna
authors.initials: H
authors.lastname: Egeröd
authors.forename: Ulf
authors.initials: U
authors.lastname: Bondesson
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wikström
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002302:Cardiac Output / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism; D007093:Imidazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011652:Pulmonary Circulation / Q000187:drug effects; D013223:Statistics as Topic; D013450:Sulfones / Q000493:pharmacokinetics / Q000627:therapeutic use; D053719:Tandem Mass Spectrometry; D014227:Triazines / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069058:Vardenafil Dihydrochloride; D014665:Vasodilator Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D007093:Imidazoles; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D014665:Vasodilator Agents; D000069058:Vardenafil Dihydrochloride