title: Transition from parenteral to oral treprostinil in pulmonary arterial hypertension.
abstract: BACKGROUND
  Parenteral prostanoids are effective treatment for pulmonary arterial hypertension, but long-term pump infusion systems have significant delivery-related safety and convenience limitations.
  
  
  METHODS
  Subjects with a favorable risk profile transitioned from parenteral to oral treprostinil using a protocol-driven titration during 5 days of inpatient observation. Baseline and Week 24 assessments included 6-minute walk distance, echocardiogram, right heart catheterization, pharmacokinetics, treatment satisfaction and quality of life. Thirty-three subjects (76% female, mean age 50 years) enrolled; 85% were using subcutaneous treprostinil with a median dose of 57 (range 25 to 111) ng/kg/min. Participants were using background, approved non-prostanoid therapy, including 9 on 2 oral therapies; baseline right atrial pressure and cardiac output were in the normal range. All 33 subjects transitioned to oral treprostinil therapy within 4 weeks, but 2 transitioned back to parenteral drug before Week 24. At Week 24, subjects were taking a median total daily dose of 44 (15 to 75) mg, with 25 of 31 using a 3-times-daily regimen at 7- to 9-hour intervals.
  
  
  RESULTS
  The 6-minute walk distance was preserved (median +17 m [-98 to 95 m]) at its baseline of 446 m. Hemodynamic variables, including pulmonary vascular resistance, were similar at Week 24 except for mixed venous saturation, which dropped from a median of 71% to 68% (p < 0.001). Overall quality of life and treatment satisfaction measures did not change; however, mood-related symptom and treatment convenience subscores improved. Common adverse effects included headache, nausea, flushing and diarrhea.
  
  
  CONCLUSIONS
  Lower risk patients managed on parenteral treprostinil may be candidates for transition to a more convenient, oral form of the drug.
authors.affiliation: Department of Medicine, Washington University, St. Louis, Missouri, USA.
authors.forename: Murali M
authors.initials: MM
authors.lastname: Chakinala
authors.affiliation: Arizona Pulmonary Specialists, Ltd, Phoenix, Arizona, USA.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Feldman
authors.affiliation: Department of Medicine, University of Arizona, Tuscon, Arizona, USA.
authors.forename: Franz
authors.initials: F
authors.lastname: Rischard
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mathier
authors.affiliation: United Therapeutics Corporation, Research Triangle Park, North Carolina, USA.
authors.forename: Meredith
authors.initials: M
authors.lastname: Broderick
authors.affiliation: United Therapeutics Corporation, Research Triangle Park, North Carolina, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Leedom
authors.affiliation: United Therapeutics Corporation, Research Triangle Park, North Carolina, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Laliberte
authors.affiliation: Division of Pulmonary and Critical Care Medicine and the Mary M. Parkes Center, University of Rochester Medical Center, University of Rochester Medical Center, Rochester, New York, USA. Electronic address: jim_white@urmc.rochester.edu.
authors.forename: R James
authors.initials: RJ
authors.lastname: White
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D011464:Epoprostenol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D065627:Familial Primary Pulmonary Hypertension / Q000175:diagnosis / Q000188:drug therapy; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy*; D007263:Infusions, Parenteral; D055104:Infusions, Subcutaneous; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011453:Prostaglandins / Q000008:administration & dosage* / Q000009:adverse effects; D011788:Quality of Life; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects*; D055815:Young Adult
chemical_list: D011453:Prostaglandins; D011464:Epoprostenol; C427248:treprostinil
keywords: hemodynamics; pharmacokinetics; pharmacology; prostaglandins; pulmonary hypertension