Roflumilast: Systemic therapy for chronic obstructive pulmonary disease

Expert Review of Respiratory Medicine

Volumn 2, Issue 5, 2008, Pages 539-549

  McIvor, R Andrew ^a  

^a MCMASTER UNIVERSITY   (Canada)

Author keywords

Chronic obstructive pulmonary disease; COPD; Exacerbation; Inflamation; Pharmacokinetics; Phosphodiesterase; Quality of life; Rofumilast

Indexed keywords

ACETYLCYSTEINE; ALUMINUM MAGNESIUM HYDROXIDE; ANTIOXIDANT; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; BUDESONIDE; CHOLINERGIC RECEPTOR BLOCKING AGENT; CILOMILAST; CORTICOSTEROID; CXCL1 CHEMOKINE; FLUVOXAMINE; GELATINASE B; INTERLEUKIN 12; INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; INTERLEUKIN 8; LEUKOTRIENE B4; MIDAZOLAM; PHOSPHODIESTERASE IV; PICLAMILAST; PLACEBO; RETINOID; ROFLUMILAST; ROLIPRAM; SALBUTAMOL; SALMETEROL; THEOPHYLLINE; TIOTROPIUM BROMIDE; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; UNINDEXED DRUG;

ANTIINFLAMMATORY ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BRONCHUS HYPERREACTIVITY; CARDIOVASCULAR DISEASE; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL TRIAL; COMORBIDITY; COST OF ILLNESS; CYTOKINE RELEASE; DIARRHEA; DISEASE EXACERBATION; DOSE RESPONSE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG COMPETITION; DRUG COST; DRUG DOSE COMPARISON; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENCY; DRUG SAFETY; DRUG SELECTIVITY; DRUG TARGETING; DRUG TOLERABILITY; DRUG WITHDRAWAL; ELECTROCARDIOGRAM; ENZYME INHIBITION; FOOD; FOOD DRUG INTERACTION; FORCED EXPIRATORY VOLUME; GASTROINTESTINAL SYMPTOM; HEALTH CARE COST; HEART ARRHYTHMIA; HEART PROTECTION; HUMAN; IC 50; MAXIMUM PLASMA CONCENTRATION; MUCUS SECRETION; NEUROLOGIC DISEASE; NONHUMAN; PATHOPHYSIOLOGY; PREVALENCE; QUALITY OF LIFE; REPEATED DRUG DOSE; RESPIRATORY TRACT INFLAMMATION; RHINOPHARYNGITIS; RISK FACTOR; SEIZURE; SIDE EFFECT; SINGLE DRUG DOSE; SYSTEMIC THERAPY; TIME TO MAXIMUM PLASMA CONCENTRATION; VITAL SIGN;

EID: 55149085636     PISSN: 17476348     EISSN: 17476356     Source Type: Journal    
DOI: 10.1586/17476348.2.5.539     Document Type: Article

References (77)

1. Weiss ST, DeMeo DL, Postma DS. COPD: problems in diagnosis and measurement. Eur. Respir. J. 41(Suppl.), 4S-12S (2003).
2. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 349(9064), 1498-1504 (1997).
3. European Respiratory Society. European Lung White Book: Huddersfield, UK. European Respiratory Society Journals, Ltd (2003).
4. Rennard SI. Antiinflammatory therapies other than corticosteroids. Proc. Am. Thorac. Soc. 1(3), 282-287 (2004).
5. Daheshia M. Pathogenesis of chronic obstructive pulmonary disease. Clin. Applied Immunol. Rev. 5(1), 339-351 (2005).
6. Sevenoaks MJ, Stockley RA. Chronic obstructive pulmonary disease, inflammation and co-morbidity - a common inflammatory phenotype? Respir. Res. 7, 70-78 (2006).
7. Larsson K. Aspects on pathophysiological mechanisms in COPD. J. Intern. Med. 262(3), 311-340 (2007).
8. Thompson AB, Daughton D, Robbins RA, Ghafouri MA, Oehlerking M, Rennard SI. Intraluminal airway inflammation in chronic bronchitis. Characterization and correlation with clinical parameters. Am. Rev. Respir. Dis. 140(6), 1527-1537 (1989).
9. Rennard SI. Chronic obstructive pulmonary disease: linking outcomes and pathobiology of disease modification. Proc. Am. Thorac. Soc. 3(3), 276-280 (2006).
10. Hogg JC, Chu S, Utokaparch R. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N. Engl. J. Med. 350(26), 2645-2653 (2004).
11. Saetta M, Di Stefano A, Maestrelli P et al. Airway eosinophilia in chronic bronchitis during exacerbations. Am. J. Respir. Crit. Care Med. 150(6 Pt 1), 1646-1652 (1994).
12. Kent L, Smyth L, Clayton C et al. Cigarette smoke extract induced cytokine and chemokine gene expression changes in COPD macrophages. Cytakine 42 (2), 205-216 (2008).
13. + T-lymphocytes in the peripheral. airways of smokers with COPD. Am. J. Respir. Crit. Care Med. 157(3 Pt 1), 822-826 (1998).
14. Peinado VI, Barbera JA, Abate P et al. Inflammatory reaction in pulmonary muscular arteries of patients with mild COPD. Am. J. Respir. Crit. Care Med. 159(5 Pt 1), 1605-1611 (1999).
15. Rennard SI. Clinical approach to patients with chronic obstructive pulmonary disease and cardiovascular disease. Proc. Am. Thorac. Soc. 2(1), 94-100 (2005).
16. Soriano JB, Visick GT, Muellerova H, Payvandi N, Hansell AL. Patterns of comorbidities in newly diagnosed COPD and asthma in primary care. Chest 128(4), 2099-2107 (2005).
17. Agustí A. Systemic effects of chronic obstructive pulmonary disease: what we know and what we don't know (but should). Proc. Am. Thorac. Soc. 4(7), 522-525 (2007).
18. Agusti A, Soriano JB. COPD as a systemic disease. COPD 5(2), 133-138 (2008).
19. Gan WQ, Man SF, Senthilselvan A, Sin DD. Association between chronic obstructive pulmonary disease and systemic infammation: a systematic review and a meta-analysis. Thorax 59(7), 574-580 (2004).
20. Pinto-Plata VM, Mullerova H, Toso JF et al. C-reactive protein in patients with COPD, control smokers and non-smokers. Thorax 61(1), 23-28 (2006).
21. Franciosi LG, Page CP, Celli BR et al. Markers of disease severity in chronic obstructive pulmonary disease. Pulm. Pharmacol. Ther. 19(3), 189-199 (2006).
22. Sin DD, Man SF. Why are patients with COPD at increased risk of cardiovascular disease? The potential role of systemic inflammation in COPD. Circulation 107(11), 1514-1519 (2003).
23. Broekhuizen R, Wouters EF, Creutzberg EC, Schols AM. Raised CRP levels mark metabolic and functional impairment in advanced COPD. Thorax 61(1), 17-22 (2006).
24. Holguin F, Folch E, Redd SC, Mannino DM. Comorbidity and mortality in COPD-related hospitalizations in the United States, 1979 to 2001. Chest 128(4), 2005-2011 (2005).
25. Curkendall SM, DeLuise C, Jones JK et al. Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients. Am. J. Epidemiol. 16(1),63-70 (2006).
26. Fabbri LM, Rabe KF. From COPD to chronic systemic inflammatory syndrome? Lancet 370(9589), 797-799 (2007).
27. Lugnier C. Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents. Pharmacol. Ther. 109(3), 366-398 (2006).
28. Vignola AM. PDE4 inhibitors in COPD - a more selective approach to treatment. Respir. Med. 98(6), 495-503 (2004).
29. Tang HF, Chen JQ, Xie QM et al. The role of PDE4 in pulmonary inflammation and goblet cell hyperplasia in allergic rats. Biochim. Biophys. Acta 1762(5), 525-532 (2006).
30. Buhl R, Farmer SG. Future directions in the pharmacologic therapy of chronic obstructive pulmonary disease. Proc. Am. Thorac. Soc. 2(1), 83-93 (2005).
31. Fan Chung K. Phosphodiesterase inhibitors in airways disease. Eur. J. Pharmacol. 533(1-3), 110-117 (2006).
32. Dinter H. Phosphodiesterase type 4 inhibitors: potential in the treatment of multiple sclerosis? BioDrugs 13(2), 87-94 (2000).
33. Hamamoto M, Suga M, Takahashi Y et al. Suppressive effect of phosphodiesterase type 4 inhibition on systemic inflammatory responses after cardiopulmonary bypass. J. Artif. Organs 9(3), 144-148 (2006).
34. Growcott EJ, Spink KG, Ren X, Afzal S, Banner KH, Wharton J. Phosphodiesterase type 4 expression and anti-proliferative effects in human pulmonary artery smooth muscle cells. Respir. Res. 7, 9 (2006).
35. Schreiber S, Keshavarzian A, Isaacs KL et al. A randomized, placebo-controlled, Phase II study of tetomilast in active ulcerative colitis. Gastroenterology 132(1), 76-86 (2007).
36. Gottlieb AB, Strober B, Krueger JG et al. An open-label, single-arm pilot study in patients with severe plaque-type psoriasis treated with an oral anti-inflammatory agent, apremilast. Curr. Med. Res. Opin. 24(5), 1529-1538 (2008).
37. Rabe KF, Bateman ED, O'Donnell D, Witte S, Bredenbröker D, Bethke TD. Roflumilast - an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 366(9485), 563-571 (2005).
38. Hatzelmann A, Schudt C. Anti-inflammatory and immunomodulatory potential of the novel PDE4 inhibitor roflumilast in vitro. J. Pharmacol. Exp. Ther. 297(1), 267-279 (2001).
39. Jones NA, Boswell-Smith V, Lever R, Page P. The effect of selective phosphodiesterase isoenzyme inhibition on neutrophil function in vitro. Pulm. Pharmacol. Ther. 18(2), 93-101 (2005).
40. Martorana PA, Beume R, Lucattelli M, Wollin L, Lungarella G. Roflumilast fully prevents emphysema in mice chronically exposed to cigarette smoke. Am. J. Respir. Crit. Care Med. 172(7), 848-853 (2005).
41. Hohlfeld JM, Schoenfeld K, Lavae-Mokhtari M et al. Roflumilast attenuates pulmonary inflammation upon segmental endotoxin challenge in healthy subjects: a randomized placebo-controlled trial. Pulm. Pharmacol. Ther. 21(4), 616-623 (2008).
42. Grootendorst DC, Gauw SA, Verhoosel RM et al. Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD. Thorax 62(12), 1081-1087 (2007).
43. Wollin L, Bundschuh DS, Wohlsen A, Marx D, Beume R. Inhibition of airway hyperresponsiveness and pulmonary inflammation by roflumilast and other PDE4 inhibitors. Pulm. Pharmacol. Ther. 19(5), 343-352 (2006).
44. Rogers DF. Physiology of airway mucus secretion and pathophysiology of hypersecretion. Respir. Care 52 (9), 1134-1146 (2007).
45. Mata M, Sarria B, Buenestado A, Cortijo J, Cerda M, Morcillo EJ. Phosphodiesterase 4 inhibition decreases MUC5AC expression induced by epidermal growth factor in human airway epithelial cells. Thorax 60(2), 144-152 (2005).
46. Kwak HJ, Song JS, Heo JY, Yang SD, Nam JY, Cheon HG. Roflumilast inhibits lipopolysaccharide-induced inflammatory mediators via suppression of nuclear factor-ΚB, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase activation. J. Pharmacol. Exp. Ther. 315(3), 1188-1195 (2005).
47. Kwak HJ, Park KM, Choi HE, Chung KS, Lim HJ, Park HY. PDE4 inhibitor, roflumilast protects cardiomyocytes against NO-induced apoptosis via activation of PKA and Epac dual pathways. Cell Signal. 20(5), 803-814 (2008).
48. Sanz MJ, Cortijo J, Taha MA et al. Roflumilast inhibits leukocyte-endothelial cell interactions, expression of adhesion molecules and microvascular permeability. Br. J. Pharmacol. 152(4), 481-492 (2007).
49. O'Brien KD, McDonald TO, Chait A, Allen MD, Alpers CE. Neovascular expression of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in human atherosclerosis and their relation to intimal leukocyte content. Circulation 93 (4), 672-682 (1996).
50. Constans J, Conri C. Circulating markers of endothelial function, in cardiovascular disease. Clin. Chim. Acta 368(1-2), 33-47 (2006).
51. Alexandraki K, Piperi C, Kalofoutis C, Singh J, Alaveras A, Kalofoutis A. Inflammatory process in Type 2 diabetes: the role of cytokines. Ann. NY Acad. Sci. 1084, 89-117 (2006).
52. Zhao YF, Feng DD, Chen C. Contribution of adipocyte-derived factors to β-cell dysfunction in diabetes. Int. J. Biochem. Cell Biol. 38 (5-6), 804-819 (2006).
53. Mundy GR. Osteoporosis and inflammation. Nutr. Rev. 65(Suppl. 12, Pt 2), S147-S151 (2007).
54. Means RT Jr. Advances in the anemia of chronic disease. Int. J. Hematol. 70 (1), 7-12 (1999).
55. David M, Zech K, Seiberling M, Weimar C, Bethke TD. Roflumilast, a novel, oral, selective PDE4 inhibitor, shows high absolute bioavailability. J. Allergy Clin. Immunol. 113(1), S220-S221 (2000).
56. Nassr N, Lahu G, von Richter O et al. Lack of a pharmacokinetic interaction between steady-state roflumilast and single-dose midazolam in healthy subjects. Br. J. Clin. Pharmacol. 63(3), 365-370 (2007).
57. Bundschuh DS, Eltze M, Barsig J, Wollin L, Hatzelmann A, Beume R. In vivo efficacy in airway disease models of roflumilast, a novel orally active PDE4 inhibitor. J. Pharmacol. Exp. Ther. 297(1), 280-290 (2001).
58. Nassr N, Lahu G, Hünnemeyer A et al. Magnesium hydroxide/ aluminium hydroxide-containing antacid does not affect the pharmacokinetics of the targeted phosphodiesterase 4 inhibitor roflumilast. J. Clin. Pharmacol. 47(5), 660-666 (2007).
59. Hauns B, Hermann R, Hünnemeyer A et al. Investigation of a potential food effect on the pharmacokinetics of roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, in healthy subjects. J. Clin. Pharmacol. 46(10), 1146-1153 (2006).
60. Böhmer GM, Hermann R, Hauns B et al. Dose-proportional intraindividual single- and repeated-dose pharmacokinetics of roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor. J. Clin. Pharmacol. 47(1), 26-36 (2007).
61. Hermann R, Siegmund W, Giessmann T et al. The oral, once-daily phosphodiesterase 4 inhibitor roflumilast lacks relevant pharmacokinetic interactions with inhaled budesonide. J. Clin. Pharmacol. 47(8), 1005-1013 (2007).
62. von Richter O, Lahu G, Huennemeyer A, Herzog R, Zech K, Hermann R. Effect of fluvoxamine on the pharmacokinetics of roflumilast and roflumilast N-oxide. Clin. Pharmacokinet. 46(7), 613-622 (2007).
63. Bethke TD, Giessmann T, Westphal K et al. Roflumilast, a once-daily oral phosphodiesterase 4 inhibitor, lacks relevant pharmacokinetic interactions with inhaled salbutamol when co-administered in healthy subjects. Int. J. Clin. Pharmacol. Ther. 44(11), 572-579 (2006).
64. Calverley PM, Sanchez-Toril F, McIvor A, Teichmann P, Bredenbroeker D, Fabbri LM. Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 176(2), 154-161 (2007).
65. Rutten-van Mölken MP, van Nooten FE, Lindemann M, Caeser M, Calverley PM. A 1-year prospective cost-effectiveness analysis of roflumilast for the treatment of patients with severe chronic obstructive pulmonary disease. Pharmacoeconomics 25(8), 695-711 (2007).
66. Man SF, Sin DD. Effects of corticosteroids on systemic inflammation in chronic obstructive pulmonary disease. Proc. Am. Thorac. Soc. 2(1), 78-82 (2005).
67. Sin DD, Man SF, Marciniuk DD et al. The effects of fluticasone with or without salmeterol on systemic biomarkers of inflammation in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 177(11), 1207-1214 (2008).
68. Powrie DJ, Wilkinson TM, Donaldson GC et al. Effect of tiotropium on sputum and serum inflammatory markers and exacerbations in COPD. Eur. Respir. J. 30(3), 472-478 (2007).
69. Boswell-Smith V, Cazzola M, Page CP. Are phosphodiesterase 4 inhibitors just more theophylline? J. Allergy Clin. Immunol. 117(6), 1237-1243 (2006).
70. Heaney LG, Lindsay JT, McGarvey LP. Inflammation in chronic obstructive pulmonary disease: implications for new treatment strategies. Curr. Med. Chem. 14(7), 787-796 (2007).
71. Calverley PM, Anderson JA, Celli B et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N. Engl. J. Med. 356(8), 775-789 (2007).
72. Wedzicha JA, Calverley PM, Seemungal TA et al. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/ fluticasone propionate or tiotropium bromide. Am. J. Respir. Crit. Care Med. 177(1), 19-26 (2008).
73. 1 in patients with COPD irrespective of smoking status. Pulm. Pharmacol. Ther. 21(1), 146-151 (2008).
74. Cazzola M, Ciaprini C, Page CP, Matera MG. Targeting systemic inflammation: novel therapies for the treatment of chronic obstructive pulmonary disease. Expert Opin. Ther. Targets 11(10), 1273-1286 (2007).
75. Maclay JD, McAllister DA, Macnee W. Cardiovascular risk in chronic obstructive pulmonary disease. Respirology 12(5), 634-641 (2007).
76. Sin DD, Anthonisen NR, Soriano JB, Agusti AG. Mortality in COPD: role of comorbidities. Eur. Respir. J. 28 (6), 1245-1257 (2006).
77. Bailey WC, Tashkin DP. Pharmacologic therapy: novel approaches for chronic obstructive pulmonary disease. Proc. Am. Thorac. Soc. 4(7), 543-548 (2007).