The potential for inhaled treprostinil in the treatment of pulmonary arterial hypertension

Therapeutic Advances in Respiratory Disease

Volumn 5, Issue 3, 2011, Pages 195-206

  Gessler, Tobias ^a   Seeger, Werner ^a   Schmehl, Thomas ^a  

^a JUSTUS LIEBIG UNIVERSITY   (Germany)

Author keywords

aerosol; inhaled treprostinil; prostanoids; pulmonary arterial hypertension; pulmonary selectivity; stable prostacyclin analogue

Indexed keywords

ILOPROST; PLACEBO; PROSTACYCLIN; UNIPROST;

BIOEQUIVALENCE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; EXERCISE; HEADACHE; HUMAN; HYPOTENSION; INHALER; INJECTION SITE PAIN; JAW PAIN; NAUSEA; PRIORITY JOURNAL; PULMONARY HYPERTENSION; REVIEW; RISK ASSESSMENT; VASODILATATION; VOMITING;

ADMINISTRATION, INHALATION; ANTIHYPERTENSIVE AGENTS; DRUG DESIGN; EPOPROSTENOL; HUMANS; HYPERTENSION, PULMONARY; MEDICATION ADHERENCE; QUALITY OF LIFE;

EID: 79957805136     PISSN: 17534658     EISSN: 17534666     Source Type: Journal    
DOI: 10.1177/1753465810397693     Document Type: Review

References (78)

1. Ahearn G.S. Selim M.A. Tapson V.F. (2002) Severe erythroderma as a complication of continuous epoprostenol therapy. Chest 122: 378–380.
2. Badesch D.B. Tapson V.F. McGoon M.D. Brundage B.H. Rubin L.J. Wigley F.M. (2000) Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann Intern Med 132: 425–434.
3. Barst R.J. Galié N. Naeije R. Simonneau G. Jeffs R. Arneson C. (2006) Long-term outcome in pulmonary arterial hypertension patients treated with subcutaneous treprostinil. Eur Respir J 28: 1195–1203.
4. Barst R.J. Rubin L.J. Long W.A. McGoon M.D. Rich S. Badesch D.B. (1996) A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. The Primary Pulmonary Hypertension Study Group. N Engl J Med 334: 296–302.
5. Barst R.J. Rubin L.J. McGoon M.D. Caldwell E.J. Long W.A. Levy P.S. (1994) Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med 121: 409–415.
6. Beck-Broichsitter M. Gauss J. Gessler T. Seeger W. Kissel T. Schmehl T. (2010) Pulmonary targeting with biodegradable salbutamol-loaded nanoparticles. J Aerosol Med Pulm Drug Deliv 23: 47–57.
7. Beck-Broichsitter M. Gauss J. Packhaeuser C.B. Lahnstein K. Schmehl T. Seeger W. (2009) Pulmonary drug delivery with aerosolizable nanoparticles in an ex vivo lung model. Int J Pharm 367: 169–178.
8. Boxer A. Allen J.M. Schmidt N. Yoder M. Baehner R.L. (1980) Inhibition of polymorphonuclear leukocyte adherence by prostacyclin. J Lab Clin Med 95: 672–678.
9. Channick R.N. Olschewski H. Seeger W. Staub T. Voswinckel R. Rubin L.J. (2006) Safety and efficacy of inhaled treprostinil as add-on therapy to bosentan in pulmonary arterial hypertension. J Am Coll Cardiol 48: 1433–1437.
10. Christman B.W. (1998) Lipid mediator dysregulation in primary pulmonary hypertension. Chest 114: 205S–207S.
11. Cremona G. Higenbottam T. (1995) Role of prostacyclin in the treatment of primary pulmonary hypertension. Am J Cardiol 75: 67A–71A.
12. Crutchley D.J. Hirsh M.J. (1991) The stable prostacyclin analog, iloprost, and prostaglandin E1 inhibit monocyte procoagulant activity in vitro. Blood 78: 382–386.
13. Czer G.T. Moser K.M. (1983) Dissociation between hemodynamic and platelet antiaggregant effects of prostacyclin in dogs determined with a rapid platelet isolation technique. J Lab Clin Med 102: 133–139.
14. Dailey L.A. Jekel N. Fink L. Gessler T. Schmehl T. Wittmar M. (2006) Investigation of the proinflammatory potential of biodegradable nanoparticle drug delivery systems in the lung. Toxicol Appl Pharmacol 215: 100–108.
15. Dailey L.A. Kleemann E. Wittmar M. Gessler T. Schmehl T. Roberts C. (2003a) Surfactant-free, biodegradable nanoparticles for aerosol therapy based on the branched polyesters, DEAPA-PVAL-g-PLGA. Pharm Res 20: 2011–2020.
16. Dailey L.A. Schmehl T. Gessler T. Wittmar M. Grimminger F. Seeger W. (2003b) Nebulization of biodegradable nanoparticles: impact of nebulizer technology and nanoparticle characteristics on aerosol features. J Control Release 86: 131–144.
17. D'Alonzo G.E. Barst R.J. Ayres S.M. Bergofsky E.H. Brundage B.H. Detre K.M. (1991) Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 115: 343–349.
18. Fijalkowska A. Kurzyna M. Torbicki A. Szewczyk G. Florczyk M. Pruszczyk P. (2006) Serum N-terminal brain natriuretic peptide as a prognostic parameter in patients with pulmonary hypertension. Chest 129: 1313–1321.
19. Galiè N. Hoeper M.M. Humbert M. Torbicki A. Vachiery J.L. Barbera J.A. (2009a) Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 34: 1219–1263.
20. Galiè N. Hoeper M.M. Humbert M. Torbicki A. Vachiery J.L. Barbera J.A. (2009b) Guidelines for the diagnosis and treatment of pulmonary hypertension: The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 2009 30: 2493–2537.
21. Gessler T. Schmehl T. Hoeper M.M. Rose F. Ghofrani H.A. Olschewski H. (2001) Ultrasonic versus jet nebulization of iloprost in severe pulmonary hypertension. Eur Respir J 17: 14–19.
22. Gessler T. Schmehl T. Olschewski H. Grimminger F. Seeger W. (2002) Aerosolized vasodilators in pulmonary hypertension. J Aerosol Med 15: 117–122.
23. Gessler T. Seeger W. Schmehl T. (2008) Inhaled prostanoids in the therapy of pulmonary hypertension. J Aerosol Med Pulm Drug Deliv 21: 1–12.
24. Gomberg-Maitland M. Tapson V.F. Benza R.L. McLaughlin V.V. Krichman A. Widlitz A.C. (2005) Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension. Am J Respir Crit Care Med 172: 1586–1589.
25. Hara S. Morishita R. Tone Y. Yokoyama C. Inoue H. Kaneda Y. (1995) Overexpression of prostacyclin synthase inhibits growth of vascular smooth muscle cells. Biochem Biophys Res Commun 216: 862–867.
26. Higenbottam T. Butt A.Y. McMahon A. Westerbeck R. Sharples L. (1998) Long-term intravenous prostaglandin (epoprostenol or iloprost) for treatment of severe pulmonary hypertension. Heart 80: 151–155.
27. Higenbottam T. Wheeldon D. Wells F. Wallwork J. (1984) Long-term treatment of primary pulmonary hypertension with continuous intravenous epoprostenol (prostacyclin). Lancet 1: 1046–1047.
28. Higenbottam T.W. Spiegelhalter D. Scott J.P. Fuster V. Dinh-Xuan A.T. Caine N. (1993) Prostacyclin (epoprostenol) and heart-lung transplantation as treatments for severe pulmonary hypertension. Br Heart J 70: 366–370.
29. Hoeper M.M. Olschewski H. Ghofrani H.A. Wilkens H. Winkler J. Borst M.M. (2000a) A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension. J Am Coll Cardiol 35: 176–182.
30. Hoeper M.M. Schwarze M. Ehlerding S. Adler-Schuermeyer A. Spiekerkoetter E. Niedermeyer J. (2000b) Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med 342: 1866–1870.
31. Hsu H.H. Rubin L.J. (2005) Iloprost inhalation solution for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother 6: 1921–1930.
32. Humbert M. Sanchez O. Fartoukh M. Jagot J.L. Le Gall C. Sitbon O. (1999) Short-term and long-term epoprostenol (prostacyclin) therapy in pulmonary hypertension secondary to connective tissue diseases: results of a pilot study. Eur Respir J 13: 1351–1356.
33. Humbert M. Sitbon O. Chaouat A. Bertocchi M. Habib G. Gressin V. (2006) Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med 173: 1023–1030.
34. Humbert M. Sitbon O. Chaouat A. Bertocchi M. Habib G. Gressin V. (2010) Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 122: 156–163.
35. Kleemann E. Schmehl T. Gessler T. Bakowsky U. Kissel T. Seeger W. (2007) Iloprost-containing liposomes for aerosol application in pulmonary arterial hypertension: formulation aspects and stability. Pharm Res 24: 277–287.
36. Laliberte K. Arneson C. Jeffs R. Hunt T. Wade M. (2004) Pharmacokinetics and steady-state bioequivalence of treprostinil sodium (Remodulin) administered by the intravenous and subcutaneous route to normal volunteers. J Cardiovasc Pharmacol 44: 209–214.
37. Lang I. Gomez-Sanchez M. Kneussl M. Naeije R. Escribano P. Skoro-Sajer N. (2006) Efficacy of long-term subcutaneous treprostinil sodium therapy in pulmonary hypertension. Chest 129: 1636–1643.
38. Le J. Ashley E.D. Neuhauser M.M. Brown J. Gentry C. Klepser M.E. (2010) Consensus summary of aerosolized antimicrobial agents: application of guideline criteria. Insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy 30: 562–584.
39. Leuchte H.H. Holzapfel M. Baumgartner R.A. Ding I. Neurohr C. Vogeser M. (2004) Clinical significance of brain natriuretic peptide in primary pulmonary hypertension. J Am Coll Cardiol 43: 764–770.
40. McLaughlin V.V. Benza R.L. Rubin L.J. Channick R.N. Voswinckel R. Tapson V.F. (2010) Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial. J Am Coll Cardiol 55: 1915–1922.
41. McLaughlin V.V. Genthner D.E. Panella M.M. Hess D.M. Rich S. (1999) Compassionate use of continuous prostacyclin in the management of secondary pulmonary hypertension: a case series. Ann Intern Med 130: 740–743.
42. McLaughlin V.V. Genthner D.E. Panella M.M. Rich S. (1998) Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension. N Engl J Med 338: 273–277.
43. McLaughlin V.V. Presberg K.W. Doyle R.L. Abman S.H. McCrory D.C. Fortin T. (2004) Prognosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 126: 78S–92S.
44. McLaughlin V.V. Shillington A. Rich S. (2002) Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation 106: 1477–1482.
45. McSwain C.S. Benza R. Shapiro S. Hill N. Schilz R. Elliott C.G. (2008) Dose proportionality of treprostinil sodium administered by continuous subcutaneous and intravenous infusion. J Clin Pharmacol 48: 19–25.
46. Moncada S. Gryglewski R. Bunting S. Vane J.R. (1976) An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263: 663–665.
47. Nagaya N. Nishikimi T. Uematsu M. Satoh T. Kyotani S. Sakamaki F. (2000) Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension. Circulation 102: 865–870.
48. O–Grady J. Warrington S. Moti M.J. Bunting S. Flower R. Fowle A.S. (1980) Effects of intravenous infusion of prostacyclin (PGI2) in man. Prostaglandins 19: 319–332.
49. Olschewski H. Ghofrani H.A. Schmehl T. Winkler J. Wilkens H. Höper M.M. (2000) Inhaled iloprost to treat severe pulmonary hypertension: an uncontrolled trial. Ann Intern Med 132: 435–443.
50. Olschewski H. Ghofrani H.A. Walmrath D. Schermuly R. Temmesfeld-Wollbrück B. Grimminger F. Seeger W. (1999) Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to lung fibrosis. Am J Respir Crit Care Med 160: 600–607.
51. Olschewski H. Ghofrani H.A. Walmrath D. Temmesfeld-Wollbrück B. Grimminger F. Seeger W. (1998) Recovery from circulatory shock in severe primary pulmonary hypertension (PPH) with aerosolization of iloprost. Intensive Care Med 24: 631–634.
52. Olschewski H. Hoeper M.M. Behr J. Ewert R. Meyer A. Borst M.M. (2010) Long-term therapy with inhaled iloprost in patients with pulmonary hypertension. Respir Med 104: 731–740.
53. Olschewski H. Rohde B. Behr J. Ewert R. Gessler T. Ghofrani H.A. (2003) Pharmacodynamics and pharmacokinetics of inhaled iloprost, aerosolized by three different devices, in severe pulmonary hypertension. Chest 124: 1294–1304.
54. Olschewski H. Simonneau G. Galié N. Higenbottam T. Naeije R. Rubin L.J. (2002) Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 347: 322–329.
55. Olschewski H. Walmrath D. Schermuly R. Ghofrani H.A. Grimminger F. Seeger W. (1996) Aerosolized prostacyclin and iloprost in severe pulmonary hypertension. Ann Intern Med 124: 820–824.
56. Opitz C.F. Wensel R. Winkler J. Halank M. Bruch L. Kleber F.X. (2005) Clinical efficacy and survival with first-line inhaled iloprost therapy in patients with idiopathic pulmonary arterial hypertension. Eur Heart J 26: 1895–1902.
57. Packhaeuser C.B. Lahnstein K. Sitterberg J. Schmehl T. Gessler T. Bakowsky U. (2009) Stabilization of aerosolizable nano-carriers by freeze-drying. Pharm Res 26: 129–138.
58. Peacock A.J. Murphy N.F. McMurray J.J. Caballero L. Stewart S. (2007) An epidemiological study of pulmonary arterial hypertension. Eur Respir J 30: 104–109.
59. Phares K.R. Weiser W.E. Miller S.P. Myers M.A. Wade M. (2003) Stability and preservative effectiveness of treprostinil sodium after dilution in common intravenous diluents. Am J Health Syst Pharm 60: 916–922.
60. Provencher S. Sitbon O. Humbert M. Cabrol S. Jaïs X. Simonneau G. (2006) Long-term outcome with first-line bosentan therapy in idiopathic pulmonary arterial hypertension. Eur Heart J 27: 589–595.
61. Robbins I.M. Christman B.W. Newman J.H. Matlock R. Loyd J.E. (1998) A survey of diagnostic practices and the use of epoprostenol in patients with primary pulmonary hypertension. Chest 114: 1269–1275.
62. Rubin L.J. Mendoza J. Hood M. McGoon M. Barst R. Williams W.B. (1990) Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial. Ann Intern Med 112: 485–491.
63. Sandifer B.L. Brigham K.L. Lawrence E.C. Mottola D. Cuppels C. Parker R.E. (2005) Potent effects of aerosol compared with intravenous treprostinil on the pulmonary circulation. J Appl Physiol 99: 2363–2368.
64. Simonneau G. Barst R.J. Galié N. Naeije R. Rich S. Bourge R.C. (2002) Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 165: 800–804.
65. Simonneau G. Robbins I. Beghetti M. Channick R.N. Delcroix M. Denton C.P. (2009) Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 54: S43's54.
66. Sitbon O. Humbert M. Nunes H. Parent F. Garcia G. Herve P. (2002) Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol 40: 780–788.
67. Sitbon O. Manes A. Jais X. Pallazini M. Humbert M. Presotto L. (2007) Rapid switch from intravenous epoprostenol to intravenous treprostinil in patients with pulmonary arterial hypertension. J Cardiovasc Pharmacol 49: 1–5.
68. Tapson V.F. Gomberg-Maitland M. McLaughlin V.V. Benza R.L. Widlitz A.C. Krichman A. (2006) Safety and efficacy of IV treprostinil for pulmonary arterial hypertension: a prospective, multicenter, open-label, 12-week trial. Chest 129: 683–688.
69. Tuder R.M. Cool C.D. Geraci M.W. Wang J. Abman S.H. Wright L. (1999) Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med 159: 1925–1932.
70. Voswinckel R. Enke B. Reichenberger F. Kohstall M. Kreckel A. Krick S. (2006a) Favorable effects of inhaled treprostinil in severe pulmonary hypertension: results from randomized controlled pilot studies. J Am Coll Cardiol 48: 1672–1681.
71. Voswinckel R. Ghofrani H.A. Grimminger F. Seeger W. Olschewski H. (2006b) Inhaled treprostinil [corrected] for treatment of chronic pulmonary arterial hypertension. Ann Intern Med 144: 149–150.
72. Voswinckel R. Reichenberger F. Enke B. Kreckel A. Krick S. Gall H. (2008) Acute effects of the combination of sildenafil and inhaled treprostinil on haemodynamics and gas exchange in pulmonary hypertension. Pulm Pharmacol Ther 21: 824–832.
73. Voswinckel R. Reichenberger F. Gall H. Schmehl T. Gessler T. Schermuly R.T. (2009) Metered dose inhaler delivery of treprostinil for the treatment of pulmonary hypertension. Pulm Pharmacol Ther 22: 50–56.
74. Whittaker N. Bunting S. Salmon J. Moncada S. Vane J.R. Johnson D.R. (1976) The chemical structure of prostaglandin X (prostacyclin). Prostaglandins 12: 915–928.
75. Walmrath D. Schneider T. Pilch J. Grimminger F. Seeger W. (1993) Aerosolized prostacyclin in adult respiratory distress syndrome. Lancet 342: 961–962.
76. Walmrath D. Schneider T. Pilch J. Schermuly R. Grimminger F. Seeger W. (1995) Effects of aerosolized prostacyclin in severe pneumonia. Impact of fibrosis. Am J Respir Crit Care Med 151: 724–730.
77. Walmrath D. Schneider T. Schermuly R. Olschewski H. Grimminger F. Seeger W. (1996) Direct comparison of inhaled nitric oxide and aerosolized prostacyclin in acute respiratory distress syndrome. Am J Respir Crit Care Med 153: 991–996.
78. Yu H. Gallagher A.M. Garfin P.M. Printz M.P. (1997) Prostacyclin release by rat cardiac fibroblasts: inhibition of collagen expression. Hypertension 30: 1047–1053.