Roflumilast: A selective phosphodiesterase 4 inhibitor

Drugs of Today

Volumn 41, Issue 10, 2005, Pages 667-675

  Christie, Pandora ^a,b  

^a UNIVERSITY OF WASHINGTON   (United States)

^b Cabrini Medical Tower ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BAY 198004; BETA ADRENERGIC RECEPTOR STIMULATING AGENT; BUDESONIDE; CIGARETTE SMOKE; CILOMILAST; CORTICOSTEROID; DEXAMETHASONE; DRUG METABOLITE; ERYTHROMYCIN; FLUTICASONE; INTERFERON; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 5; LEUKOTRIENE B4; MATRIX METALLOPROTEINASE; MUCIN; PHOSPHODIESTERASE INHIBITOR; PHOSPHODIESTERASE IV; PHOSPHODIESTERASE IV INHIBITOR; PICLAMILAST; PLACEBO; ROFLUMILAST; ROLIPRAM; SALBUTAMOL; THEOPHYLLINE; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNINDEXED DRUG; WARFARIN;

ABDOMINAL PAIN; ANTIINFLAMMATORY ACTIVITY; ASTHMA; BRONCHOSPASM; CHRONIC OBSTRUCTIVE LUNG DISEASE; DIARRHEA; DIZZINESS; DOSE RESPONSE; DRUG EFFICACY; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; ENZYME INHIBITION; FATIGUE; FORCED EXPIRATORY VOLUME; HEADACHE; HUMAN; IMMUNE RESPONSE; LUNG FUNCTION TEST; NAUSEA; NONHUMAN; REVIEW; SLEEP DISORDER; TREATMENT OUTCOME;

3',5'-CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; AMINOPYRIDINES; ANIMALS; ANTI-INFLAMMATORY AGENTS; BENZAMIDES; CYCLOPROPANES; HUMANS; LUNG DISEASES, OBSTRUCTIVE; MOLECULAR STRUCTURE; PHOSPHODIESTERASE INHIBITORS;

EID: 30444451489     PISSN: 16993993     EISSN: 16994019     Source Type: Journal    
DOI: 10.1358/dot.2005.41.10.920428     Document Type: Review

References (46)

1. Torphy, T.J. Phosphodiesterase isozymes: Molecular targets for novel antiasthma agents. Am J Respir Crit Care Med 1998, 157: 351-70.
2. Spina, D. Phosphodiesterase-4 inhibitors in the treatment of inflammatory lung disease. Drugs 2003, 63: 2575-94.
3. Manning, C.D., Burman, M., Christensen, S.B. et al. Suppression of human inflammatory cell function by subtype-selective PDE4 inhibitors correlates with inhibition of PDE4A and PDE4B. Br J Pharmacol 1999, 128: 1393-8.
4. Robichaud, A., Stamatiou, P.B., Jin, S.-L.C. et al. Deletion of phosphodiesterase 4D in mice shortens alpha2-adrenoceptor-mediated anesthesia, a behavioral correlate of emesis. J Clin Invest 2002, 110: 1045-52.
5. Jin, S.-L.C., Conti, M. Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-alpha responses. Proc Nat Acad Sci USA 2002, 99: 7628-33.
6. Souness, J.E., Aldous, D., Sargent, C. Immunosuppressive and anti-inflammatory effects of cyclic AMP phosphodiesterase (PDE) type 4 inhibitors. Immunopharmacology 2000, 47: 127-62
7. Bousquet, J., Jeffery, P.K., Busse, W.W. et al. Asthma from bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med 2000, 161: 1720-45.
8. Sutherland, E.R., Martin, R.J. Airway inflammation in chronic obstructive pulmonary disease: Comparison with asthma. J Allergy Clin Immunol 2003, 112: 819-27
9. Barnes, P.J. Theophylline: New perspectives for an old drug. Am J Respir Crit Care Med 2003, 167: 813-8.
10. Castro, A., Jerez, M.J., Gil, C. et al. Cyclic nucleotide phosphodiesterases and their role in immunomodulatory responses: Advances in the development of specific phosphodiesterase inhibitors. Med Res Rev 2005, 25: 229-44
11. Schmidt, B.M.W., Kusma, M., Feuring, M. et al. The phosphodiesterase 4 inhibitor roflumilast is effective in the treatment of allergic rhinitis. J Allergy Clin Immunol 2001, 108: 530-6.
12. Banner, K.H., Trevethick, M.A. PDE4 inhibition: A novel approach for the treatment of inflammatory bowel disease. Trends Pharmacol Sci 2004, 25: 430-6.
13. Hatzelmann, A., Schudt, C. Anti-Inflammatory and immunomodulatory potential of the novel PDE4 inhibitor roflumilast in vitro. J Pharmacol Exp Ther 2001, 297: 267-79.
14. Jones, N.A., Boswell-Smith, V., Lever, R. et al. The effect of selective phosphodiesterase isoenzyme inhibition on neutrophil function in vitro. Pulm Pharmacol Ther 2005, 18: 93-101.
15. Mata, M., Sarria, B., Buenestado, A. et al. Phosphodiesterase 4 inhibition decreases MUC5AC expression induced by epidermal growth factor in human airway epithelial cells. Thorax 2005, 60: 144-152.
16. Bundschuh, D.S., Eltze, M., Barsig, J., et al. In vivo efficacy in airway disease models of roflumilast, a novel orally active PDE4 inhibitor. J Pharmacol Exp Ther 2001, 297: 280-90
17. Kumar, R.K., Herbert, C., Thomas, P.S. et al. Inhibition of inflammation and remodeling by roflumilast and dexamethasone in murine chronic asthma. J Pharmacol Exp Ther 2003, 307: 349-55.
18. Crouch, E. Pathobiology of pulmonary fibrosis. Am J Lung Cell Mol Physiol 1990, 259: L159-84.
19. Segura-Valdez, L., Pardo, A., Gaxiola, M. et al. Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD. Chest 2000, 117: 684-94.
20. Sasaki, M., Kashima, M., Ito, T. et al. Differential regulation of metalloproteinases production proliferation and chemotaxis of human lung fibroblasts by PDGF, interleukin-1b and TNF-alpha. Mediators Inflam 2000, 9: 155-60.
21. Zhu, Y.K., Liu, X.D., Skold, C.M. et al. Synergistic neutrophil elastase-cytokine interaction degrades collagen in three-dimensional culture. Am J Physiol Lung Cell Mol Physiol 2001, 281: L868-78.
22. Corbel, M., Germain, N., Lanchou, J. et al. The active phosphodiesterase 4 inhibitor PP 73-401 reduced matrix metalloproteinase 9 activity and TGF-beta release during acute lung injury in mice: The role of the balance between tumor necrosis factor-alpha and interleukin-10. J Pharmacol Exp Ther 2002, 301: 258-65.
23. Kohyama, T., Liu, X., Wen, F.Q. et al. PDE4 inhibitors attenuate fibroblast chemotaxis and contraction of native collagen gels. Am J Respir Cell Mol Biol 2002, 26: 694-701.
24. Martorana, P.A., 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 2005, in press.
25. Muise, E.S., Chute, I.C., Claveau, D. et al. Comparison of inhibition of ovalbumin-induced bronchoconstriction in guinea pigs and in vitro inhibition of tumor necrosis factor-alpha formation with phosphodiesterase 4 (PDE4) selective inhibitors. Biochem Pharmacol 2002, 63: 1527-35.
26. Manegold, A., Hauns, B., David, M. et al. Pharmacokinetic characteristics of roflumilast administered in gradually increasing doses of 500 meg to 1000 meg are dose linear in healthy subjects. Eur Respir J 2002, S38: 108S.
27. Manegold, A.M., Zech, K., Hauns, B. et al. Pharmacokinetics of roflumilast and its active metabolite roflumilast N-oxide in middle aged and young subjects. Eur Respir J 2002, 20: 744.
28. Zech, K. High oral soluble bioavailability of roflumilast, a new, orally active, once daily PDE4 inhibitor. Eur Respir J 2001, 18: Abst 256.
29. Drollman, A., Hauns, B., David, M. et al. Pharmacokinetic characteristics of roflumilast and its active metabolite roflumilast-N-oxide are not affected by food intake. Eur Respir J 2002, 20 (Suppl. 38): 108s.
30. Drollmann, A. M., Zech, K., David, M. et al. Patients with severe renal impairment do not require dose adjustment of roflumilast. Eur Respir J 2002, 20: 743.
31. Bethke, T.H., Zech, K., David, M. et al. No dose adjustment of roflumilast in patients with severe renal impairment. 98th Int Conf Am Thorac Soc 2002, (May 17-22, Atlanta), Abst C90.
32. van Schalkvyk, E.M., Nell, H., van Heerden, K. et al. Inhibition of the late asthmatic reaction in allergic asthma by the novel, selective PDE4 inhibitor roflumilast. J Allergy Clin Imunol 2004, 113: P785.
33. Nell, H., Louw, C., Leichtl, S. et al. Acute antiinflammatory effect of the novel phosphodiesterase 4 inhibitor roflumilast on allergen challenge in asthmatics after a single dose. Am J Respir Crit Care Med 2000, 161 (3 part 2): A200.
34. Timmer, W., Leclerc, V., Birraux, G. et al. The new phosphodiesterase 4 inhibitor roflumilast is efficacious in exercise-induced asthma and leads to suppression of LPS-stimulated TNF-alpha ex vivo. J Clin Pharmacol 2002, 42: 297-303.
35. Giembycz, M.A. Development status of second generation PDE4 inhibitors for asthma and COPD: The story so far. Monaldi Arch Chest Dis 2002, 57: 48-64.
36. Izquierdo, J.L., Bateman, E.D., Vilasante, et al. Long-term efficacy and safety over one year of once-daily roflumilast, a new orally active, selective phosphodiesterase 4 inhibitor, in asthma. Am J Respir Crit Care Med 2003, 167: A765.
37. Aubier, M. Sauer, R., Boszormenyi Nagy, G. et al. Roflumilast, a novel selective PDE4 inhibitor, shows early onset of efficacy in asthma. Am J Respir Crit Care Med 2004, 169: A322.
38. Roflumilast BY-217. Drugs Fut 2001, 26: 1215-6.
39. Bredenbrsker, D., Syed, S., Leichtl, S. et al. Roflumilast, a new orally active, selective phosphodiesterase-4 inhibitor, is effective in the treatment of chronic obstructive pulmonary disease. Eur Respir J 2002, 20 (Suppl. 38): P374S.
40. Rabe, K.F., Chapman, K.R., Jubert, J. et al. Roflumilast, a novel selective phosphodiesterase inhibitor, improves lung function in patients with moderate to severe COPD. Am J Respir Crit Care Med 2004, 169: A518.
41. O'Donnell, D., Muir, J.S., Jenkins, C. et al. Roflumilast, a novel selective phosphodiesterase 4 inhibitor improves quality of life and lowers exacerbation rates in patients with moderate to severe COPD. Am J Respir Crit Care Med 2004, 169: A602.
42. Hauns, B., Hunnemeyer, A., Siegmund, W. et al. Pharmacokinetics of the selective PDE4 inhibitor roflumilast and its active metabolite roflumilast N-oxide are not affected by concomitant budesonide, salbutamol, or erythromycin. J Allergy Clin Immunol 2004, 113: P786.
43. Huennemeyer, A., Zech, K., Boehner, G. et al. Roflumilast shows no pharmacokinetic interaction with warfarin in healthy subjects. Chest 2004, 126: 804s.
44. Suva, P.M., Alves, A.C., Serra, M.F. et al. Modulation of eotaxin formation and eosinophil migration by selective inhibitors of phosphodiesterase type 4 isoenzyme. Br J Pharmacol 2001, 134: 283-94.
45. Pang, L., Knox, A.J. Synergistic inhibition by beta(2)-agonists and corticosteroids on tumor necrosis factor-alpha induced interleukin-8 release from cultured human airway smooth muscle cells. Am J Respir Cell Mol Biol 2000, 23: 79-85.
46. Hatzelmann, A., Schudt, C. Anti-inflammatory and immunomodulatory potential of the novel PDE4 inhibitor roflumilast in vitro. J Pharmacol Exp Ther 2001, 297: 267-79.