Iloprost inhalation solution for the treatment of pulmonary arterial hypertension

Expert Opinion on Pharmacotherapy

Volumn 6, Issue 11, 2005, Pages 1921-1930

  Hsu, Henry H ^a   Rubin, Lewis J ^b  

^a CoTherix Inc ^*  (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Iloprost; Prostacyclin analogues; Pulmonary arterial hypertension

Indexed keywords

ANTIMITOTIC AGENT; BERAPROST; BOSENTAN; ENDOTHELIN; ENDOTHELIN A RECEPTOR ANTAGONIST; ENDOTHELIN RECEPTOR ANTAGONIST; ILOPROST; MITOGENIC AGENT; NITRIC OXIDE; PLACEBO; PROSTACYCLIN; PROSTACYCLIN DERIVATIVE; SILDENAFIL; UNIPROST; VASODILATOR AGENT;

BACKACHE; BLEEDING; CAUSE OF DEATH; CLINICAL TRIAL; CONGESTIVE HEART FAILURE; COUGHING; DISEASE EXACERBATION; DIZZINESS; DRUG APPROVAL; DRUG BLOOD LEVEL; DRUG DELIVERY SYSTEM; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG ERUPTION; DRUG FATALITY; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG POTENTIATION; DRUG SOLUTION; DRUG STABILITY; DRUG SYNTHESIS; DRUG TARGETING; DYSPNEA; FLU LIKE SYNDROME; FLUSHING; HEART MUSCLE CONDUCTION DISTURBANCE; HEART PALPITATION; HEART RIGHT VENTRICLE FAILURE; HEMATOLOGIC DISEASE; HEMOPTYSIS; HUMAN; HYPOTENSION; INSOMNIA; KIDNEY FAILURE; LUNG ARTERY PRESSURE; LUNG VASCULAR RESISTANCE; METABOLIC DISORDER; MUSCLE CRAMP; MUSCLE WEAKNESS; NAUSEA; PALLOR; PERIPHERAL EDEMA; PNEUMONIA; PULMONARY HYPERTENSION; REBOUND; REVIEW; SMOOTH MUSCLE; SUPRAVENTRICULAR TACHYCARDIA; SYNCOPE; THORAX PAIN; TONGUE DISEASE; TRISMUS; VASCULAR ENDOTHELIUM; VOMITING;

ADMINISTRATION, INHALATION; ANIMALS; FEMALE; HUMANS; HYPERTENSION, PULMONARY; ILOPROST; MALE; MIDDLE AGED; PLATELET AGGREGATION INHIBITORS; PULMONARY CIRCULATION; RANDOMIZED CONTROLLED TRIALS; SOLUTIONS; VASCULAR RESISTANCE; VASODILATOR AGENTS;

EID: 25444498926     PISSN: 14656566     EISSN: None     Source Type: Journal    
DOI: 10.1517/14656566.6.11.1921     Document Type: Review

References (67)

1. RUBIN LJ: Diagnosis and management of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest (2004) 126(1 Suppl.):7S-10S.
2. [NO AUTHORS LISTED]: Proceedings of the 3rd World Symposium on pulmonary arterial hypertension. Venice, Italy June 23-25 2003. J. Am. Coll. Cardiol. (2004) 43(12 Suppl. S):1S-90S.
3. MANDEGAR M, FUNG YC, HUANG W et al.: Cellular and molecular mechanisms of pulmonary vascular remodeling: role in the development of pulmonary hypertension. Microvasc. Res. (2004) 68(2):75-103.
4. HUMBERT M, MORRELL NW, ARCHER SL et al.: Cellular and molecular pathobiology of pulmonary arterial hypertension. J. Am. Coll. Cardiol. (2004) 43(12 Suppl. S):13S-24S.
5. CHRISTMAN BW, MCPHERSON CD, NEWMAN JH et al.: An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N. Engl. J. Med. (1992) 327(2):70-75.
6. HAYWOOD GA, ADAMS KF JR, GHEORGHIADE M, MCKENNA WJ: Is there a role for epoprostenol in the management of heart failure? Am. J. Cardiol. (1995) 75(3):44A-50A.
7. OLSCHEWSKI H, GHOFRANI HA, WALMRATH D et al.: Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to lung fibrosis. Am. J. Respir. Crit. Care Med. (1999) 160(2):600-607.
8. SEREGI A, SCHOBERT A, HERTTING G: The stable prostacyclin-analogue, iloprost, unlike prostanoids and leukotrienes, potently stimulates cyclic adenosine monophosphate synthesis of primary astroglial cell cultures. J. Pharm. Pharmacol. (1988) 40(6):437-438.
9. LEIGH PJ, CRAMP WA, MACDERMOT J: Identification of the prostacyclin receptor by radiation inactivation. J. Biol. Chem. (1984) 259(20):12431-12436.
10. VANE JR, BOTTING RM: Pharmacodynamic profile of prostacyclin. Am. J. Cardiol. (1995) 75(3):3A-10A.
11. SANIABADI AR, BELCH JJ, LOWE GD, BARBENEL JC, FORBES CD: Comparison of inhibitory actions of prostacyclin and a new prostacyclin analogue on the aggregation of human platelet in whole blood. Haemostasis (1987) 17(3):147-153.
12. WHARTON J, DAVIE N, UPTON PD, YACOUB MH, POLAK JM, MORRELL NW: Prostacyclin analogues differentially inhibit growth of distal and proximal human pulmonary artery smooth muscle cells. Circulation (2000) 102(25):3130-3136.
13. CLAPP LH, FINNEY P, TURCATO S, TRAN S, RUBIN LJ, TINKER A: 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.
14. LI RC, CINDROVA-DAVIES T, SKEPPER JN, SELLERS LA: 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):759-767.
15. OLSCHEWSKI H, ROSE F, GRUNIG E, GHOFRANI HA: Cellular pathophysiology and therapy of pulmonary hypertension. J. Lab. Clin. Med. (2001) 138(6):367-377.
16. SCHERMULY RT, KREISSELMEIER KP, GHOFRANI HA et al.: Antiremodeling effects of iloprost and the dual-selective phosphodiesterase 3/4 inhibitor tolafentrine in chronic experimental pulmonary hypertension. Circ. Res. (2004) 94(8):1101-1108.
17. IOANNOU P, TALESNIK J: Platelet antiaggregatory substances inhibit arachidonic acid induced coronary constriction. Can. J. Physiol. Pharmacol. (1986) 64(4):398-405.
18. MULLER B, SCHMIDTKE M, WITT W: Action of the stable prostacyclin analogue iloprost on microvascular tone and permeability in the hamster cheek pouch. Prostaglandins Leukot. Med. (1987) 29(2-3):187-198.
19. SCHULZ BG, MULLER B: Iloprost antagonizes endothelin-induced vasoconstriction in macro- and microcirculation. Eicosanoids (1990) 3(3):135-138.
20. OZAKI H, ABE A, UEHIGASHI Y et al.: Effects of a prostaglandin 12 analog iloprost on cytoplasmic Ca2+ levels and muscle contraction in isolated guinea pig aorta. Jpn. J. Pharmacol (1996) 71(3):231-237.
21. SCHUBERT R, SEREBRYAKOV VN, MEWES H, HOPP HH: Iloprost dilates rat small arteries: role of K(ATP)- and K(Ca)-channel activation by cAMP-dependent protein kinase. Am. J. Physiol. (1997) 272(3 Pt 2):H1147-H1156.
22. COWLEY AJ, HEPTINSTALL S, HAMPTON JR: Effects of prostacyclin and of the stable prostacyclin analogue ZK 36374 on forearm blood flow and blood platelet behaviour in man. Thromb. Haemost. (1985) 53(1):90-94.
23. GROOM TM, GAUTIERI RF: Influence of a stable prostacyclin analogue (iloprost) and cyclooxygenase inhibition on angiotensin-II in the perfused human placenta. Res. Commun. Chem. Pathol. Pharmacol. (1989) 66(1):21-32.
24. GRUNER S, BECKER K, VOLK HD, VON BAEHR R, LANGKOPF B, FORSTER W: Immunomodulatory effects of iloprost in vitro and in vivo comparison with various Prostaglandins. Prog. Clin. Biol. Res. (1987) 242:345-350.
25. MULLER B, SCHMIDTKE M, WITT W: Adherence of leucocytes to electrically damaged venules in vivo. Effects of iloprost PGE1, indomethacin, forskolin BW 755 C, sulotroban, hirudin, and thrombocytopenia. Eicosanoids (1988) 1(1):13-17.
26. NEY P, HECKER G, SCHRODER H, SCHROR K: Potent inhibition of leukotriene (LT) B4 release from human polymorphonuclear leukocytes (PMN) by the PGE1-analogue OP-1206. Biomed. Biochim. Acta (1988) 47(10-11):S186-S189.
27. KORBUT R, TRABKA-JANIK E, GRYGLEWSKI RJ: Cytoprotection of human polymorphonuclear leukocytes by stimulators of adenylate and guanylate cyclases. Eur. J. Pharmacol. (1989) 165(1):171-172.
28. MAZZONE A, MAZZUCCHELLI I, FOSSATI G et al.: Iloprost effects on phagocytes in patients suffering from ischaemic diseases: in vivo evidence for down-regulation of alpha M beta 2 integrin. Eur. J. Clin. Invest. (1996) 26(10):860-866.
29. KAPPA JR, HORN MK III, FISHER CA, COTTRELL ED, ELLISON N, ADDONIZIO VP Jr: Efficacy of iloprost (ZK36374) versus aspirin in preventing heparin-induced platelet activation during cardiac operations. J. Thorac. Cardiovasc. Surg. (1987) 94(3):405-413.
30. WITT W, MULLER B: Antithrombotic profile of iloprost in experimental models of in vivo platelet aggregation and thrombosis. Adv. Prostaglandin Thromboxane Leukot. Res. (1987) 17A:279-284.
31. SHANBERGE JN, KAJIWARA Y, QUATTROCIOCCHI-LONGE T: Effect of aspirin and iloprost on adhesion of platelets to intact endothelium in vivo. J. Lab. Clin. Med. (1995) 125(1):96-101.
32. OLSCHEWSKI H, ROHDE B, BEHR J et al.: Pharmacodynamics and pharmacokinetics of inhaled iloprost, aerosolized by three different devices, in severe pulmonary hypertension. Chest (2003) 124(4):1294-1304.
33. SCHERMULY RT, SCHULZ A, GHOFRANI HA et al.: Pharmacokinetics and metabolism of infused versus inhaled iloprost in isolated rabbit lungs. J. Pharmacol. Exp. Ther. (2002) 303(2):741-745.
34. KRAUSE W, KRAIS T: Pharmacokinetics and pharmacodynamics of radio-labeled iloprost in elderly volunteers. Eur. J. Clin. Pharmacol. (1987) 32(6):597-605.
35. KRAUSE W, HUMPEL M, HOYER BA: Biotransformation of the stable prostacyclin analogue, iloprost, in the rat. Drug Metab. Dispos. (1984) 12(5):645-651.
36. OLSCHEWSKI H, WALMRATH D, SCHERMULY R, GHOFRANI A, GRIMMINGER F, SEEGER W: Aerosolized prostacyclin and iloprost in severe pulmonary hypertension. Ann. Intern. Med. (1996) 124(9):820-824.
37. HOEPER MM, OLSCHEWSKI H, GHOFRANI HA et al.: A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension. German PPH study group. J. Am. Coll. Cardiol. (2000) 35(1):176-182.
38. OLSCHEWSKI H, GHOFRANI HA, SCHMEHL T et al.: Inhaled iloprost to treat severe pulmonary hypertension. An uncontrolled trial. German PPH Study Group. Ann. Intern. Med. (2000) 132(6):435-443.
39. GESSLER T, SCHMEHL T, HOEPER MM et al.: Ultrasonic versus jet nebulization of iloprost in severe pulmonary hypertension. Eur. Respir. J. (2001) 17(1):14-19.
40. OLSCHEWSKI H, SIMONNEAU G, GALIE N et al.: Inhaled iloprost for severe pulmonary hypertension. N. Engl. J. Med. (2002) 347(5):322-329.
41. PETTERSEN E, MORSTOL TH, VEGSUNDVAG JA: Long-term echocardiographic follow-up of a patient with primary pulmonary hypertension receiving iloprost inhalations. Eur. J. Echocardiogr. (2005) 6(1):67-71.
42. LEUCHTE HH, SCHWAIBLMAIR M, BAUMGARTNER RA, NEUROHR CF, KOLBE T, BEHR J: Hemodynamic response to sildenafil, nitric oxide, and iloprost in primary pulmonary hypertension. Chest (2004) 125(2):580-586.
43. HALANK M, MARX C, MIEHLKE S, HOEFFKEN G: Use of aerosolized inhaled iloprost in the treatment of portopulmonary hypertension. J. Gastroenterol. (2004) 39(12):1222-1223.
44. GHOFRANI HA, FRIESE G, DISCHER T et al.: Inhaled iloprost is a potent acute pulmonary vasodilator in HIV-related severe pulmonary hypertension. Eur. Respir. J. (2004) 23(2):321-326.
45. OPITZ CF, WENSEL R, BETTMANN M et al.: Assessment of the vasodilator response in primary pulmonary hypertension. Comparing prostacyclin and iloprost administered by either infusion or inhalation. Eur. Heart J. (2003) 24(4):356-365.
46. LEUCHTE HH, BAUMGARTNER RA, BEHR J: Treatment of severe pulmonary hypertension with inhaled iloprost. Ann. Intern. Med. (2003) 139(4):306.
47. KRAMM T, EBERLE B, KRUMMENAUER F, GUTH S, OELERT H, MAYER E: Inhaled iloprost in patients with chronic thromboembolic pulmonary hypertension: effects before and after pulmonary thromboendarterectomy. Ann. Thorac. Surg. (2003) 76(3):711-718.
48. HALLIOGLU O, DILBER E, CELIKER A: Comparison of acute hemodynamic effects of aerosolized and intravenous iloprost in secondary pulmonary hypertension in children with congenital heart disease. Am. J. Cardiol. (2003) 92(8):1007-1009.
49. FRUHWALD FM, KJELLSTROM B, PERTHOLD W et al.: Continuous hemodynamic monitoring in pulmonary hypertensive patients treated with inhaled iloprost. Chest (2003) 124(1):351-359.
50. EHLEN M, WIEBE B: Iloprost in persistent pulmonary hypertension of the newborn. Cardiol. Young (2003) 13(4):361-363.
51. GHOFRANI HA, WIEDEMANN R, ROSE F et al.: Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension. Ann. Intern. Med. (2002) 136(7):515-522.
52. BLUMBERG FC, RIEGGER GA, PFEIFER M: Hemodynamic effects of aerosolized iloprost in pulmonary hypertension at rest and during exercise. Chest (2002) 121(5):1566-1571.
53. WILKENS H, GUTH A, KONIG J et al.: Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation (2001) 104(11):1218-1222.
54. WENSEL R, OPITZ CF, EWERT R, BRUCH L, KLEBER FX: Effects of iloprost inhalation on exercise capacity and ventilatory efficiency in patients with primary pulmonary hypertension. Circulation (2000) 101(20):2388-2392.
55. HOEPER MM, 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):1866-1870.
56. OLSCHEWSKI H: Safety, dosing, and clinical benefit of 2-year therapy with inhaled iloprost. American Thoracic Society Meeting. San Diego, USA (2005) [A57] [Poster: K29].
57. OPITZ CF, WENSEL R, WINKLER J et al.: Clinical efficacy and survival with first-line inhaled iloprost therapy in patients with idiopathic pulmonary arterial hypertension. Eur. Heart. J. (2005) [Epub ahead of print].
58. D'ALONZO GE, BARST RJ, AYRES SM et al.: Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann. Intern. Med. (1991) 115(5):343-349.
59. CUIPER LL, PRICE PV, CHRISTMAN BW: Systemic and pulmonary hypertension after abrupt cessation of prostacyclin: role of thromboxane A2. J. Appl. Physiol. (1996) 80(1):191-197.
60. SCHULZE-NEICK I, WERNER H, PENNY DJ, ALEXI-MESKISHVILI V, LANGE PE: Acute ventilatory restriction in children after weaning off inhaled nitric oxide: relation to rebound pulmonary hypertension. Intensive Care Med. (1999) 25(1):76-80.
61. PEARL JM, NELSON DP, RAAKE JL et al.: Inhaled nitric oxide increases endothelin-1 levels: a potential cause of rebound pulmonary hypertension. Crit. Care Med. (2002) 30(1):89-93.
62. NIKANDER K, ARHEDEN L, DENYER J, COBOS N: Parents' adherence with nebulizer treatment of their children when using an adaptive aerosol delivery (AAD) system. J. Aerosol Med. (2003) 16(3):273-281.
63. NIKANDER K, DENYER J, SMITH N, WOLLMER P: Breathing patterns and aerosol delivery: impact of regular human patterns, and sine and square waveforms on rate of delivery. J. Aerosol Med. (2001) 14(3):327-333.
64. NIKANDER K, TURPEINEN M, WOLLMER P: Evaluation of pulsed and breath-synchronized nebulization of budesonide as a means of reducing nebulizer wastage of drug. Pediatr Pulmonol (2000) 29(2):120-126.
65. NIKANDER K, AGERTOFT L, PEDERSEN S: Breath-synchronized nebulization diminishes the impact of patient-device interfaces (face mask or mouthpiece) on the inhaled mass of nebulized budesonide. J. Asthma (2000) 37(5):451-459.
66. HOEPER MM, TAHA N, BEKJAROVA A, GATZKE R, SPIEKERKOETTER E: Bosentan treatment in patients with primary pulmonary hypertension receiving nonparenteral prostanoids. Eur. Respir. J. (2003) 22(2):330-334.
67. GHOFRANI HA, ROSE F, SCHERMULY RT et al.: Oral sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension. J. Am. Coll. Cardiol. (2003) 42(1):158-164.