title: Acute effects of the combination of sildenafil and inhaled treprostinil on haemodynamics and gas exchange in pulmonary hypertension.
abstract: BACKGROUND
  Inhaled treprostinil was recently developed for the treatment of pulmonary arterial hypertension (PAH). We investigated the safety and acute haemodynamic effects of the combination oral sildenafil and inhaled treprostinil in an open label study in patients with precapillary pulmonary hypertension.
  
  
  METHODS
  Inhaled nitric oxide (20ppm; n=50), sildenafil (50mg; n=50) and inhaled treprostinil (15microg; n=25 or 30microg; n=25) were applied in subsequent order during right heart catheter investigation to consecutive patients with pulmonary arterial hypertension (PAH; n=28), non-operable chronic thromboembolic pulmonary hypertension (CTEPH; n=17) and pulmonary fibrosis associated pulmonary hypertension (n=5).
  
  
  RESULTS
  Inhaled nitric oxide reduced pulmonary vascular resistance (PVR) to 87.3+/-5.1% of baseline values, reduced mean pulmonary arterial pressure (PAP) to 89.7+/-3.5% and increased cardiac output (CO) to 102.4+/-2.9%. Sildenafil reduced PVR to 80.1+/-5.0%, mPAP to 86.5+/-2.9% and increased CO to 103.8+/-3.2%. Treprostinil, inhaled 1h after sildenafil, reduced PVR to 66.3+/-3.8%, mPAP to 77.8+/-3.3%, and increased CO to 107.1+/-3.3% (mean+/-95% confidence interval). Subgroup analysis showed similar acute haemodynamic effects in PAH and CTEPH patients. Ventilation/perfusion distribution measurement in six patients with pre-existing gas exchange limitations was not changed by sildenafil and treprostinil. Relevant side effects were not observed.
  
  
  CONCLUSIONS
  The combination of sildenafil and inhaled treprostinil was well tolerated and induced additive, pulmonary selective vasodilatation in pulmonary hypertension patients. This could be of relevance also for long-term treatment of PAH and CTEPH patients.
authors.affiliation: Department of Internal Medicine, University of Giessen Lung Center, University Hospital Giessen and Marburg GmbH, Giessen, Germany. robert.voswinckel@innere.med.uni-giessen.de
authors.forename: Robert
authors.initials: R
authors.lastname: Voswinckel
authors.forename: Frank
authors.initials: F
authors.lastname: Reichenberger
authors.forename: Beate
authors.initials: B
authors.lastname: Enke
authors.forename: Andre
authors.initials: A
authors.lastname: Kreckel
authors.forename: Stefanie
authors.initials: S
authors.lastname: Krick
authors.forename: Henning
authors.initials: H
authors.lastname: Gall
authors.forename: Ralph Theo
authors.initials: RT
authors.lastname: Schermuly
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Rubin
authors.forename: Horst
authors.initials: H
authors.lastname: Olschewski
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.forename: Hossein A
authors.initials: HA
authors.lastname: Ghofrani
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D003371:Cough / Q000139:chemically induced; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D010879:Piperazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011658:Pulmonary Fibrosis / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D011687:Purines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D011464:Epoprostenol; C427248:treprostinil