Pharmacologic and pharmacokinetic rationale for combination therapy in pulmonary arterial hypertension

Journal of Cardiovascular Pharmacology

Volumn 56, Issue 6, 2010, Pages 686-695

  Gokhman, Roman ^a   Smithburger, Pamela L ^b   Kane Gill, Sandra L ^a,b   Seybert, Amy L ^a,b  

^a UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

^b UNIVERSITY OF PITTSBURGH   (United States)

Author keywords

Combination therapy; Eendothelin antagonist; Pharmacokinetics; Phosphodiesterase inhibitor; Prostanoid; Pulmonary arterial hypertension

Indexed keywords

AMBRISENTAN; BOSENTAN; ENDOTHELIN; ILOPROST; NITRIC OXIDE; PROSTACYCLIN; SILDENAFIL; TADALAFIL; UNIPROST;

ARTICLE; BIOEQUIVALENCE; CONTINUOUS INFUSION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DOSE INCREASE; DRUG DOSE TITRATION; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; HUMAN; MAXIMUM PLASMA CONCENTRATION; PRIORITY JOURNAL; PULMONARY HYPERTENSION; STEADY STATE;

ANIMALS; ANTIHYPERTENSIVE AGENTS; CLINICAL TRIALS AS TOPIC; DRUG THERAPY, COMBINATION; ENDOTHELINS; EPOPROSTENOL; HUMANS; HYPERTENSION, PULMONARY;

EID: 78751643714     PISSN: 01602446     EISSN: None     Source Type: Journal    
DOI: 10.1097/FJC.0b013e3181f89bdb     Document Type: Article

References (69)

1. Rubin LJ. Diagnosis and management of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004;126 (Suppl 1):S7-S10.
2. Chin KM, Rubin LJ. Pulmonary arterial hypertension. J Am Coll Cardiol. 2008;51:1527-1538.
3. 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;115:343-349.
4. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351:1425-1436.
5. McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation. 2002;106: 1477-1482.
6. Barst RJ, Rubin LJ, Long WA, 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;334:296-302.
7. Highland KB. Pulmonary arterial hypertension. Am J Med Sci. 2008;335: 40-45.
8. Badesch DB, Abman SH, Simonneau G, et al. Medical therapy for pulmonary arterial hypertension: updated ACCP evidence-based clinical practice guidelines. Chest. 2007;131:1917-1928.
9. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc, and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009;53:1573-1619.
10. Barst RJ, Gibbs JS, Ghofrani HA, et al. Updated evidence-based treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol. 2009; 54(Suppl 1):S78-S84.
11. Rich S, Kaufmann E, Levy PS. The effect of high doses of calciumchannel blockers on survival in primary pulmonary hypertension. N Engl Med. 1992;327:76-81.
12. 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;327:70-75.
13. Tuder RM, Cool CD, Geraci MW, et al. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med. 1999;159:1925-1932.
14. Flolan [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2008.
15. Remodulin [package insert]. Bloomington, IN: Baxter Pharmaceutical Solution Corp; 2008.
16. Ventavis [package insert]. San Francisco, CA: Actelion Pharmaceuticals US Inc; 2008.
17. Revatio [package insert]. New York, NY: Pfizer Inc; 2007.
18. Adcirca [package insert]. Indianapolis, IN: Eli Lily & Company; 2009.
19. Corbin J, Francis S, Zoraghi R. Tyrosine-612 in PDE5 contributes to higher affinity for vardenafil over sildenafil. Int J Impot Res. 2005;18:251-257.
20. Ghofrani H-A, Voswinckel R, Gall H, et al. Riociguat for pulmonary hypertension. Future Cardiol. 2010;6:155-166.
21. Giaid A, Yanagisawa M, Langleben D, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med. 1993; 328:1732-1739. (Pubitemid 23170122)
22. Kedzierski RM, Yanagisawa M. Endothelin system: the double-edged sword in health and disease. Annu Rev Pharmacol Toxicol. 2001;41:851-876.
23. Opitz CF, Ewert R. Dual ET(A)/ET(B) versus selective ET(A) endothelin receptor antagonism in patients with pulmonary hypertension. Eur J Clin Invest. 2006;36(Suppl 3):1-9.
24. Nishida M, Eshiro K, Okada Y, et al. Roles of endothelin ETA and ETB receptors in the pathogenesis of monocrotaline-induced pulmonary hypertension. J Cardiovasc Pharmacol. 2004;44:187-191. (Pubitemid 38982161)
25. Tracleer [package insert]. South San Francisco, CA: Actelion Pharmaceuticals US Inc; 2009.
26. Letairis [package insert]. Foster City, CA: Gilead Sciences Inc; 2009.
27. Benza RL, Park MH, Keogh A, et al. Management of pulmonary arterial hypertension with a focus on combination therapies. J Heart Lung Transplant. 2007;26:437-446.
28. D'Alto M, Alfano D, Maiello C, et al. Complex multidrug therapy in a patient with pulmonary hypertension before and after orthotopic heart transplantation. A case report. J Cardiovasc Med (Hagerstown). 2007;8: 950-952.
29. Minai OA, Arroliga AC. Long-term results after addition of sildenafil in idiopathic PAH patients on bosentan. South Med J. 2006;99:880-883.
30. Bennett JA, Riegel B, Bittner V, et al. Validity and reliability of the NYHA classes for measuring research outcomes in patients with cardiac disease. Heart Lung. 2002;31:262-270.
31. Sitbon O, Humbert M, Simonneau G. Primary pulmonary hypertension: current therapy. Prog Cardiovasc Dis. 2002;45:115-128. (Pubitemid 35253678)
32. Tyvaso [package insert].Woodstock, IL: United Therapeutics Corp; 2009.
33. Actelion Web site. February 23, 2009. Available at: http://www.actelion. com/en/our-company/news-and-events/index.page?newsId=1292312. Accessed May 1, 2010.
34. Olschewski H, Rose F, Schermuly R, et al. Prostacyclin and its analogues in the treatment of pulmonary hypertension. Pharmacol Ther. 2004;102: 139-153. (Pubitemid 38681013)
35. Mathai SC, Girgis RE, Fisher MR, et al. Addition of sildenafil to bosentan monotherapy in pulmonary arterial hypertension. Eur Respir J. 2007;29: 469-475.
36. Treiber A, Schneiter R, Hausler S, et al. Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos. 2007;35:1400-1407.
37. Dingemanse J, van Giersbergen PL. Clinical pharmacology of bosentan, a dual endothelin receptor antagonist. Clin Pharmacokinet. 2004;43: 1089-1115.
38. Cada DJ, Levien T, Baker DE. Ambrisentan. Hosp Pharm. 2007;42: 1145-1151.
39. Hoeper MM, Taha N, Bekjarova A, et al. Bosentan treatment in patients with primary pulmonary hypertension receiving nonparenteral prostanoids. Eur Respir J. 2003;22:330-334.
40. Humbert M, Barst RJ, Robbins IM, et al. Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J. 2004;24:353-359. (Pubitemid 39232254)
41. Seyfarth HJ, Pankau H, Hammerschmidt S, et al. Bosentan improves exercise tolerance and Tei index in patients with pulmonary hypertension and prostanoid therapy. Chest. 2005;128:709-713.
42. Hoeper MM, Markevych I, Spiekerkoetter E, et al. Goal-oriented treatment and combination therapy for pulmonary arterial hypertension. Eur Respir J. 2005;26:858-863.
43. Channick RN, Olschewski H, Seeger W, et al. Safety and efficacy of inhaled treprostinil as add-on therapy to bosentan in pulmonary arterial hypertension. J Am Coll Cardiol. 2006;48:1433-1437.
44. McLaughlin VV, Oudiz RJ, Frost A, et al. Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2006;174:1257-1263.
45. Hoeper MM, Leuchte H, Halank M, et al. Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension. Eur Respir J. 2006;28:691-694.
46. Benza RL, Rayburn BK, Tallaj JA, et al. Treprostinil-based therapy in the treatment of moderate-to-severe pulmonary arterial hypertension: longterm efficacy and combination with bosentan. Chest. 2008;134:139-145.
47. Akagi S, Matsubara H, Miyaji K, et al. Additional effects of bosentan in patients with idiopathic pulmonary arterial hypertension already treated with high-dose epoprostenol. Circ J. 2008;72:1142-1146.
48. Austin MJ,McDougall NI,Wendon JA, et al. Safety and efficacy of combined use of sildenafil, bosentan, and iloprost before and after liver transplantation in severe portopulmonary hypertension. Liver Transpl. 2008;14:287-291.
49. Jacobs W, Boonstra A, Marcus JT, et al. Addition of prostanoids in pulmonary hypertension deteriorating on oral therapy. J Heart Lung Transplant. 2009;28:280-284.
50. Pitsiou GG, Chavouzis N, Nakou C, et al. Successful up-front combination therapy in a patient with idiopathic pulmonary hypertension and patent foramen ovale: an alternative to epoprostenol therapy? J Heart Lung Transplant. 2009;28:651-653.
51. Stiebellehner L, Petkov V, Vonbank K, et al. Long-term treatment with oral sildenafil in addition to continuous IV epoprostenol in patients with pulmonary arterial hypertension. Chest. 2003;123:1293-1295.
52. 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;42:158-164.
53. Kataoka M, Satoh T, Manabe T, et al. Oral sildenafil improves primary pulmonary hypertension refractory to epoprostenol. Circ J. 2005;69:461-465.
54. Gomberg-Maitland M, McLaughlin V, Gulati M, et al. Efficacy and safety of sildenafil added to treprostinil in pulmonary hypertension. Am J Cardiol. 2005;96:1334-1336.
55. Reichenberger F, Voswinckel R, Steveling E, et al. Sildenafil treatment for portopulmonary hypertension. Eur Respir J. 2006;28:563-567.
56. Ruiz MJ, Escribano P, Delgado JF, et al. Efficacy of sildenafil as a rescue therapy for patients with severe pulmonary arterial hypertension and given long-term treatment with prostanoids: 2-year experience. J Heart Lung Transplant. 2006;25:1353-1357.
57. Onen ZP, Akkoca Yildiz O, Eris Gulbay B, et al. Inhaled iloprost as a longterm additional therapy to oral sildenafil in severe idiopathic pulmonary arterial hypertension. Tuberk Toraks. 2006;54:177-181.
58. Miwa K, Matsubara T, Uno Y, et al. Combination therapy with oral sildenafil and beraprost for pulmonary arterial hypertension associated with CREST syndrome. Int Heart J. 2007;48:417-422.
59. Bendayan D, Shitrit D, Kramer MR. Combination therapy with prostacyclin and tadalafil for severe pulmonary arterial hypertension: a pilot study. Respirology. 2008;13:916-918.
60. Simonneau G, Rubin LJ, 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;149:521-530.
61. Hoeper MM, Faulenbach C, Golpon H, et al. Combination therapy with bosentan and sildenafil in idiopathic pulmonary arterial hypertension. Eur Respir J. 2004;24:1007-1010.
62. Galie N, Rubin L, Hoeper M, et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet. 2008;371: 2093-2100.
63. Faruqi S, Fathi H, Morice AH. Combination of sitaxentan and tadalafil for idiopathic pulmonary arterial hypertension following relapse on bosentan. Int J Cardiol. 2010;144:e43-e45.
64. Galie NMD, Brundage BHMD, Ghofrani HAMD, et al; on behalf of the Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) Study Group. Tadalafil therapy for pulmonary arterial hypertension. Circulation. 2009;119:2894-2903.
65. Burgess G, Hoogkamer H, Collings L, et al. Mutual pharmacokinetic interactions between steady-state bosentan and sildenafil. Eur J Clin Pharmacol. 2008;64:43-50.
66. Wrishko RE, Dingemanse J, Yu A, et al. Pharmacokinetic interaction between tadalafil and bosentan in healthy male subjects. J Clin Pharmacol. 2008;48:610-618.
67. Humbert M, Segal ES, Kiely DG, et al. Results of European postmarketing surveillance of bosentan in pulmonary hypertension. Eur Respir J. 2007;30:338-344.
68. Paul GA, Gibbs JS, Boobis AR, et al. Bosentan decreases the plasma concentration of sildenafil when coprescribed in pulmonary hypertension. Br J Clin Pharmacol. 2005;60:107-112.
69. Gruenig E, Michelakis E, Vachiery JL, et al. Acute hemodynamic effects of single-dose sildenafil when added to established bosentan therapy in patients with pulmonary arterial hypertension: results of the COMPASS-1 study. J Clin Pharmacol. 2009;49:1343-1352.