Pharmacokinetic evaluation of continuous intravenous epoprostenol

Expert Opinion on Drug Metabolism and Toxicology

Volumn 6, Issue 12, 2010, Pages 1587-1598

  Chaumais, Marie Camille ^a,b,c   Jobard, Marion ^a,b   Huertas, Alice ^a,b,c   Vignand Courtin, Claire ^a,b   Humbert, Marc ^a,b,c   Sitbon, Olivier ^a,b,c   Rieutord, André ^a,b   Montani, David ^a,b,c  

^a UNIVERSITÉ PARIS SACLAY   (France)

^b HÔPITAL ANTOINE BÉCLÈRE   (France)

^c CENTRE CHIRURGICAL MARIE LANNELONGUE   (France)

Author keywords

Epoprostenol; Pharmacokinetics; Prostacyclin; Pulmonary arterial hypertension

Indexed keywords

AMBRISENTAN; BERAPROST; BOSENTAN; ILOPROST; PROSTACYCLIN; SILDENAFIL; SITAXSENTAN; TADALAFIL; UNIPROST;

ANXIETY; BACTEREMIA; BODY FLUID; CELLULITIS; CLINICAL TRIAL; CONTINUOUS INFUSION; DIARRHEA; DRUG EFFICACY; DRUG FORMULATION; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; ERYTHRODERMA; EXERCISE; FLUSHING; HEADACHE; HUMAN; HYPERGLYCEMIA; HYPERTHYROIDISM; JAW DISEASE; MEDLINE; MUSCULOSKELETAL PAIN; NAUSEA; NONHUMAN; PHARMACODYNAMICS; PHOTOSENSITIVITY; PULMONARY HYPERTENSION; RESTLESSNESS; REVIEW; SEPSIS; SIDE EFFECT; STAPHYLOCOCCUS AUREUS; STEADY STATE; THORAX PAIN; VEIN THROMBOSIS;

EID: 78649261508     PISSN: 17425255     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425255.2010.534458     Document Type: Review

References (105)

1. Bos C, Richel D, Ritsema T, et al. Prostanoids and prostanoid receptors in signal transduction. Int J Biochem Cell Biol 2004;36(7):1187-205
2. Vane J, Corin R. Prostacyclin: a vascular mediator. Eur J Vasc Endovasc Surg 2003;26(6):571-8 •• Description of the main properties of prostacyclin (vasodilator and anti-thrombotic).
3. Vane J, Anggard E, Botting R. Regulatory functions of the vascular endothelium. N Engl J Med 1990;323(1):27-36
4. McLaughlin V, McGoon M. Pulmonary arterial hypertension. Circulation 2006;114(13):1417-31
5. Rubin L. Primary pulmonary hypertension. N Engl J Med 1997;336(2):111-17 • The first article grouping description of the three factors involving in the physiopathology of PAH.
6. Christman B, McPherson C, Newman J, et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med 1992;327(2):70-5 •• The first study showing the prostacyclin diminution in PAH patients.
7. Moncada S, Gryglewski R, Bunting S, et al. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 1976;263(5579):663-5 •• A paper on prostacyclin discovery by of investigators led by Nobel prize winner John Vane.
8. Whittaker N, Bunting S, Salmon J, et al. The chemical structure of prostaglandin X (prostacyclin). Prostaglandins 1976;12(6):915-28
9. Gryglewski R. Prostaglandins, platelets, and atherosclerosis. CRC Crit Rev Biochem 1980;7(4):291-338
10. 2 leading to administered epoprostenol by continuous intravenous route.
11. Gomberg-Maitland M, Olschewski H. Prostacyclin therapies for the treatment of pulmonary arterial hypertension. Eur Respir J 2008;31(4):891-901
12. Vane J, Bakhle Y, Botting R. Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 1998;38:97-120
13. Marcus A, Weksler B, Jaffe E, et al. Synthesis of prostacyclin from platelet-derived endoperoxides by cultured human endothelial cells. J Clin Invest 1980;66(5):979-86 (Pubitemid 11233798)
14. Bunting S, Gryglewski R, Moncada S, et al. Arterial walls generate from prostaglandin endoperoxides a substance (prostaglandin X) which relaxes strips of mesenteric and coeliac ateries and inhibits platelet aggregation. Prostaglandins 1976;12(6):897-913
15. Langleben D, Barst R, Badesch D, et al. Continuous infusion of epoprostenol improves the net balance between pulmonary endothelin-1 clearance and release in primary pulmonary hypertension. Circulation 1999;99(25):3266-71
16. Prins B, Hu R, Nazario B, et al. Prostaglandin E2 and prostacyclin inhibit the production and secretion of endothelin from cultured endothelial cells. J Biol Chem 1994;269(16):11938-44
17. Fetalvero K, Martin K, Hwa J. Cardioprotective prostacyclin signaling in vascular smooth muscle. Prostaglandins Other Lipid Mediat 2007;82(1-4): 109-18 (Pubitemid 44895439)
18. Wharton J, Davie N, Upton P, et al. Prostacyclin analogues differentially inhibit growth of distal and proximal human pulmonary artery smooth muscle cells. Circulation 2000;102(25):3130-6
19. Li R, Cindrova-Davies T, Skepper J, et al. Prostacyclin induces apoptosis of vascular smooth muscle cells by a cAMP-mediated inhibition of extracellular signal-regulated kinase activity and can counteract the mitogenic activity of endothelin-1 or basic fibroblast growth factor. Circ Res 2004;94(6):759-67
20. Moncada S, Vane J. Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2, and prostacyclin. Pharmacol Rev 1978;30(3):293-331
21. Kothapalli D, Stewart S, Smyth E, et al. Prostacylin receptor activation inhibits proliferation of aortic smooth muscle cells by regulating cAMP response element-binding protein-and pocket protein-dependent cyclin a gene expression. Mol Pharmacol 2003;64(2):249-58
22. Clapp L, Finney P, Turcato S, et al. Differential effects of stable prostacyclin analogs on smooth muscle proliferation and cyclic AMP generation in human pulmonary artery. Am J Respir Cell Mol Biol 2002;26(2):194-201
23. Sinzinger H, Fitscha P, Kritz H. Antimitotic actions of vasodilatory prostaglandins - clinical aspects. Agents Actions Suppl 1997;48:92-106
24. Olschewski H, Olschewski A, Rose F, et al. Physiologic basis for the treatment of pulmonary hypertension. J Lab Clin Med 2001;138(5):287-97
25. Zardi E, Zardi D, Cacciapaglia F, et al. Endothelial dysfunction and activation as an expression of disease: role of prostacyclin analogs. Int Immunopharmacol 2005;5(3):437-59
26. Araki H, Lefer A. Role of prostacyclin in the preservation of ischemic myocardial tissue in the perfused cat heart. Circ Res 1980;47(5):757-63 (Pubitemid 11238274)
27. Ogletree M, Lefer A, Smith J, et al. Studies on the protective effect of prostacyclin in acute myocardial ischemia. Eur J Pharmacol 1979;56(1-2): 95-103 (Pubitemid 9202747)
28. Montalescot G, Drobinski G, Meurin P, et al. Effects of prostacyclin on the pulmonary vascular tone and cardiac contractility of patients with pulmonary hypertension secondary to end-stage heart failure. Am J Cardiol 1998;82(6):749-55
29. Rich S, McLaughlin V. The effects of chronic prostacyclin therapy on cardiac output and symptoms in primary pulmonary hypertension. J Am Coll Cardiol 1999;34(4):1184-7
30. Wauthy P, Abdel Kafi S, Mooi W, et al. Inhaled nitric oxide versus prostacyclin in chronic shunt-induced pulmonary hypertension. J Thorac Cardiovasc Surg 2003;126(5):1434-41
31. Rex S, Missant C, Segers P, et al. Epoprostenol treatment of acute pulmonary hypertension is associated with a paradoxical decrease in right ventricular contractility. Intensive Care Med 2008;34(1):179-89
32. Narumiya S, Sugimoto Y, Ushikubi F. Prostanoid receptors: structures, properties, and functions. Physiol Rev 1999;79(4):1193-226
33. Adie E, Mullaney I, McKenzie F, et al. Concurrent down-regulation of IP prostanoid receptors and the alpha-subunit of the stimulatory guanine-nucleotide-binding protein (Gs) during prolonged exposure of neuroblastoma x glioma cells to prostanoid agonists. Quantification and functional implications. Biochem J 1992;285(Pt 2):529-36
34. Hartshorne D, Ito M, Erdodi F. Myosin light chain phosphatase: subunit composition, interactions and regulation. J Muscle Res Cell Motil 1998;19(4):325-41
35. Wise H. Multiple signalling options for prostacyclin. Acta Pharmacol Sin 2003;24(7):625-30
36. Abramovitz M, Adam M, Boie Y, et al. The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim Biophys Acta 2000;1483(2):285-93
37. Hatae T, Wada M, Yokoyama C, et al. Prostacyclin-dependent apoptosis mediated by PPAR delta. J Biol Chem 2001;276(49):46260-7
38. Walch L, Labat C, Gascard J, et al. Prostanoid receptors involved in the relaxation of human pulmonary vessels. Br J Pharmacol 1999;126(4):859-66 (Pubitemid 29103701)
39. Tuder R, Cool C, Geraci M, et al. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med 1999;159(6):1925-32 •• The first study proving diminution of prostacyclin expression in lungs from PAH patients.
40. Geraci M, Gao B, Shepherd D, et al. Pulmonary prostacyclin synthase overexpression in transgenic mice protects against development of hypoxic pulmonary hypertension. J Clin Invest 1999;103(11):1509-15
41. Tahara N, Kai H, Niiyama H, et al. Repeated gene transfer of naked prostacyclin synthase plasmid into skelet al. muscles attenuates monocrotaline-induced pulmonary hypertension and prolongs survival in rats. Hum Gene Ther 2004;15(12):1270-8
42. Friedman R, Mears J, Barst R. Continuous infusion of prostacyclin normalizes plasma markers of endothelial cell injury and platelet aggregation in primary pulmonary hypertension. Circulation 1997;96(9):2782-4
43. Schermuly RT, Pullamsetti SS, Breitenbach SC, et al. Iloprost-induced desensitization of the prostacyclin receptor in isolated rabbit lungs. Respir Res 2007;8:4
44. Smyth E, Austin S, Reilly M, et al. Internalization and sequestration of the human prostacyclin receptor. J Biol Chem 2000;275(41):32037-45
45. McLaughlin V, Genthner D, Panella M, et al. Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension. N Engl J Med 1998;338(5):273-7 (Pubitemid 28065252)
46. Benedict N, Seybert A, Mathier M. Evidence-based pharmacologic management of pulmonary arterial hypertension. Clin Ther 2007;29(10):2134-53 (Pubitemid 350138566)
47. Brash A, Jackson E, Saggese C, et al. Metabolic disposition of prostacyclin in humans. J Pharmacol Exp Ther 1983;226(1):78-87 •• A study contributing to a greater knowledge of pharmacokinetics epoprostenol.
48. Herner S, Mauro L. Epoprostenol in primary pulmonary hypertension. Ann Pharmacother 1999;33(3):340-7 •• A study allowing metabolites activities of epoprostenol.
49. Witchey-Lakshmanan L, Palepu N, Teja BB. A novel formulation of epoprostenol with antimicrobial properties, administered under ambient conditions, for treatment of patients with pulmonary arterial hypertension. Am J Respir Crit Care Med 2010;181: A3364 • An abtract presenting a new formulation of epoprostenol leading to a greater epoprostenol stability and patients's quality of life.
50. Laliberte K, Arneson C, Jeffs R, et al. Pharmacokinetics and steady-state bioequivalence of treprostinil sodium (Remodulin) administered by the intravenous and subcutaneous route to normal volunteers. J Cardiovasc Pharmacol 2004;44(2):209-14
51. Mubarak K. A review of prostaglandin analogs in the management of patients with pulmonary arterial hypertension. Respir Med 2010;104(1):9-21
52. Hoeper M, Schwarze M, Ehlerding S, et al. Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med 2000;342(25):1866-70 (Pubitemid 30419050)
53. Krause W, Krais T. Pharmacokinetics and pharmacodynamics of the prostacyclin analogue iloprost in man. Eur J Clin Pharmacol 1986;30(1):61-8 (Pubitemid 16166985)
54. Galie N, Manes A, Branzi A. The new clinical trials on pharmacological treatment in pulmonary arterial hypertension. Eur Respir J 2002;20(4):1037-49
55. Barst R, McGoon M, McLaughlin V, et al. Beraprost therapy for pulmonary arterial hypertension. J Am Coll Cardiol 2003;41(12):2119-25 (Pubitemid 36724255)
56. Galie N, Humbert M, Vachiery J, et al. Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol 2002;39(9):1496-502
57. Galie N, Hoeper M, Humbert M, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 2009;34(6):1219-63 • Recent guidelines for PAH treatment maintaining epoprostenol as a 'gold-standard' therapy.
58. Galie N, Hoeper M, Humbert M, et al. 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(20):2493-537
59. Montani D, O'Callaghan D, Jais X, et al. Implementing the ESC/ERS pulmonary hypertension guidelines: real-life cases from a national referral centre. Eur Respir Rev 2009;18(114):231-49
60. Badesch D, McLaughlin V, Delcroix M, et al. Prostanoid therapy for pulmonary arterial hypertension. J Am Coll Cardiol 2004;43(12 Suppl S): 56S-61S (Pubitemid 38759718)
61. Higenbottam T, Wheeldon D, Wells F, et al. Long-term treatment of primary pulmonary hypertension with continuous intravenous epoprostenol (prostacyclin). Lancet 1984;1(8385):1046-7 • The first case report using continuous intravenous epoprostenol in a PAH patient.
62. Rubin L, Mendoza J, Hood M, et al. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial. Ann Intern Med 1990;112(7):485-91
63. Barst R, Rubin L, McGoon M, et al. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med 1994;121(6):409-15
64. Barst R, Rubin L, Long W, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. The Primary Pulmonary Hypertension Study Group. N Engl J Med 1996;334(5):296-302 • A pivotal trial leading to FDA acceptation on USA for continuous intravenous epoprostenol in the treatment of PAH.
65. Shapiro S, Oudiz R, Cao T, et al. Primary pulmonary hypertension: improved long-term effects and survival with continuous intravenous epoprostenol infusion. J Am Coll Cardiol 1997;30(2):343-9
66. Sitbon O, Humbert M, Nunes H, et al. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol 2002;40(4):780-8
67. McLaughlin V, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation 2002;106(12):1477-82
68. Badesch D, Tapson V, McGoon M, et al. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann Intern Med 2000;132(6):425-34
69. Humbert M, Sanchez O, Fartoukh M, et al. Short-term and long-term epoprostenol (prostacyclin) therapy in pulmonary hypertension secondary to connective tissue diseases: results of a pilot study. Eur Respir J 1999;13(6):1351-6
70. Klings E, Hill N, Ieong M, et al. Systemic sclerosis-associated pulmonary hypertension: short-and long-term effects of epoprostenol (prostacyclin). Arthritis Rheum 1999;42(12):2638-45
71. McLaughlin V, Genthner D, Panella M, et al. Compassionate use of continuous prostacyclin in the management of secondary pulmonary hypertension: a case series. Ann Intern Med 1999;130(9):740-3
72. Rosenzweig E, Kerstein D, Barst R. Long-term prostacyclin for pulmonary hypertension with associated congenital heart defects. Circulation 1999;99(14):1858-65
73. Kuo P, Johnson L, Plotkin J, et al. Continuous intravenous infusion of epoprostenol for the treatment of portopulmonary hypertension. Transplantation 1997;63(4):604-6
74. Krowka M, Frantz R, McGoon M, et al. Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): a study of 15 patients with moderate to severe portopulmonary hypertension. Hepatology 1999;30(3):641-8
75. Aguilar R, Farber H. Epoprostenol (prostacyclin) therapy in HIV-associated pulmonary hypertension. Am J Respir Crit Care Med 2000;162(5):1846-50
76. Nunes H, Humbert M, Sitbon O, et al. Prognostic factors for survival in human immunodeficiency virus-associated pulmonary arterial hypertension. Am J Respir Crit Care Med 2003;167(10):1433-9
77. Cabrol S, Souza R, Jais X, et al. Intravenous epoprostenol in inoperable chronic thromboembolic pulmonary hypertension. J Heart Lung Transplant 2007;26(4):357-62
78. Higenbottam T, Butt A, McMahon A, et al. Long-term intravenous prostaglandin (epoprostenol or iloprost) for treatment of severe pulmonary hypertension. Heart 1998;80(2):151-5
79. Montani D, Price L, Dorfmuller P, et al. Pulmonary veno-occlusive disease. Eur Respir J 2009;33(1):189-200
80. Montani D, Jais X, Price L, et al. Cautious epoprostenol therapy is a safe bridge to lung transplantation in pulmonary veno-occlusive disease. Eur Respir J 2009;34(6):1348-56
81. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med 2004;351(14):1425-36 •• State-of-art treatment of PAH allowing potential interest of association with epoprostenol and an agent acting on another pathway.
82. Humbert M, Barst RJ, Robbins IM, et al. Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J 2004;24(3):353-9 (Pubitemid 39232254)
83. Simonneau G, Rubin L, Galie N, et al. Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial. Ann Intern Med 2008;149(8):521-30
84. Barst R, Berman-Rosenzweig E, Horn E. Bloodstream infections among patients treated with intravenous eporpostenol or intravenous treprostinil for pulmonary arterial hypertension-seven sites, United States, 2003-2006. Morb Mortal Wkly Rep 2007;56:170-2 •• A study reporting high risk infections with epoprostenol route.
85. Kallen A, Lederman E, Balaji A, et al. Bloodstream infections in patients given treatment with intravenous prostanoids. Infect Control Hosp Epidemiol 2008;29(4):342-9
86. Zaccardelli D, Phares K, Jeffs R, et al. Stability and antimicrobial effectiveness of treprostinil sodium in Sterile Diluent for Flolan. Int J Clin Pract 2010;64(7):885-91
87. Oudiz R, Widlitz A, Beckmann X, et al. Micrococcus-associated central venous catheter infection in patients with pulmonary arterial hypertension. Chest 2004;126(1):90-4
88. O'Callaghan DS, Moutet A, Jais X, et al. Catheter realted-infections in pulmonary hypertension patients treated by continuous intravenous epoprostenol: experience if the French Referral Centre. Am J Respir Crit Care Med 2010;181: A3337
89. Doran A, Ivy D, Barst R, et al. Guidelines for the prevention of central venous catheter-related blood stream infections with prostanoid therapy for pulmonary arterial hypertension. Int J Clin Pract Suppl 2008; (160):5-9
90. Kingman M, Tankersley M, Lombardi S, et al. Prostacyclin administration errors in pulmonary arterial hypertension patients admitted to hospitals in the United States: a national survey. J Heart Lung Transplant 2010;29(8):841-6 •• A recent study underlining difficulties on drug delivery system of epoprostenol administration leading to administration errors.
91. Chin K, Channick R, de Lemos J, et al. Hemodynamics and epoprostenol use are associated with thrombocytopenia in pulmonary arterial hypertension. Chest 2009;135(1):130-6
92. Magnani B, Galie N. Prostacyclin in primary pulmonary hypertension. Eur Heart J 1996;17(1):18-24
93. Ahearn G, Selim M, Tapson V. Severe erythroderma as a complication of continuous epoprostenol therapy. Chest 2002;122(1):378-80
94. Szczeklik A, Pieton R, Sieradzki J, et al. The effects of prostacyclin on glycemia and insulin release in man. Prostaglandins 1980;19(6):959-68
95. Montani D, Achouh L, Dorfmuller P, et al. Pulmonary veno-occlusive disease: clinical, functional, radiologic, and hemodynamic characteristics and outcome of 24 cases confirmed by histology. Medicine (Baltimore) 2008;87(4):220-33
96. Montani D, O'Callaghan DS, Savale L, et al. Pulmonary veno-occlusive disease: recent progress and current challenges. Respir Med 2010;104: S23-32
97. Huang S, DeSantis E. Treatment of pulmonary arterial hypertension in pregnancy. Am J Health Syst Pharm 2007;64(18):1922-6
98. Bedard E, Dimopoulos K, Gatzoulis M. Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension? Eur Heart J 2009;30(3):256-65
99. Bildirici I, Shumway J. Intravenous and inhaled epoprostenol for primary pulmonary hypertension during pregnancy and delivery. Obstet Gynecol 2004;103(5 Pt 2):1102-5
100. Stewart R, Tuazon D, Olson G, et al. Pregnancy and primary pulmonary hypertension: successful outcome with epoprostenol therapy. Chest 2001;119(3):973-5
101. Price L, Montani D, Jais X, et al. Noncardiothoracic nonobstetric surgery in mild-to-moderate pulmonary hypertension. Eur Respir J 2010;35(6):1294-302
102. McLaughlin V, Gaine S, Barst R, et al. Efficacy and safety of treprostinil: an epoprostenol analog for primary pulmonary hypertension. J Cardiovasc Pharmacol 2003;41(2):293-9
103. Oudiz R, Farber H. Dosing considerations in the use of intravenous prostanoids in pulmonary arterial hypertension: an experience-based review. Am Heart J 2009;157(4):625-35
104. Higenbottam T, Butt A, Dinh-Xaun A, et al. Treatment of pulmonary hypertension with the continuous infusion of a prostacyclin analogue, iloprost. Heart 1998;79(2):175-9
105. Jacobs W, Vonk-Noordegraaf A. Epoprostenol in pulmonary arterial hypertension. Expert Opin Drug Metab Toxicol 2009;5(1):83-90