Cilomilast: A second generation phosphodiesterase 4 inhibitor for asthma and chronic obstructive pulmonary disease

Expert Opinion on Investigational Drugs

Volumn 10, Issue 7, 2001, Pages 1361-1379

  Giembycz, M A ^a  

^a NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

Author keywords

Airways inflammation; Ariflo; Asthma; Chronic obstructive pulmonary disease; Cilomilast; Cyclic AMP; Phosphodiesterase 4; SB 207499

Indexed keywords

1 [6 CHLORO 4 (3,4 METHYLENEDIOXYBENZYLAMINO) 2 QUINAZOLINYL] 4 PIPERIDINECARBOXYLIC ACID; 3 (3 CYCLOPENTYLOXY 4 METHOXYBENZYL) 6 ETHYLAMINO 8 ISOPROPYL 3H PURINE; 4 (3 CHLOROPHENYL) 1,7 DIETHYLPYRIDO[2,3 D]PYRIMIDIN 2(1H) ONE; BAY 19 8004; CILOMILAST; CORTICOSTEROID; CYCLIC AMP; DIGOXIN; N (3,5 DICHLORO 1 OXIDO 4 PYRIDINYL) 8 METHOXY 2 TRIFLUOROMETHYL 5 QUINOLINECARBOXAMIDE; PD 189659; PHOSPHODIESTERASE IV; PHOSPHODIESTERASE IV INHIBITOR; PLACEBO; ROFLUMILAST; ROLIPRAM; SALBUTAMOL; SCH 351951; THEOPHYLLINE; UNCLASSIFIED DRUG; V 11294 A; WARFARIN; YM 9762;

ABDOMINAL PAIN; ADULT; AGED; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ASTHMA; BRONCHITIS; CATALYSIS; CENTRAL NERVOUS SYSTEM; CHRONIC OBSTRUCTIVE LUNG DISEASE; CIGARETTE SMOKING; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; COST EFFECTIVENESS ANALYSIS; DIARRHEA; DISEASE EXACERBATION; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG BINDING SITE; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG EXPOSURE; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG PENETRATION; DRUG POTENTIATION; DRUG SAFETY; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TOLERABILITY; DYSPEPSIA; FEMALE; HEADACHE; HUMAN; IMMUNOCOMPETENT CELL; IN VITRO STUDY; INFLAMMATORY CELL; INSOMNIA; LUNG FUNCTION; MALE; MULTICENTER STUDY; NAUSEA AND VOMITING; NONHUMAN; PATHOGENESIS; PH; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PHASE 3 CLINICAL TRIAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; RHINITIS; SUPRAVENTRICULAR PREMATURE BEAT; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION;

3',5'-CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; BRONCHODILATOR AGENTS; CARBON RADIOISOTOPES; CARBOXYLIC ACIDS; DRUG INTERACTIONS; DRUG TOLERANCE; HUMANS; LUNG DISEASES, OBSTRUCTIVE; MALE; NITRILES; PHOSPHODIESTERASE INHIBITORS;

EID: 0034942625     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.10.7.1361     Document Type: Article

References (126)

1. Pulmonary Diseases. Disease Trends and Market Opportunities
2. Differences and similarities between chronic obstructive pulmonary disease and asthma
3. A national estimate of the economic costs of asthma
4. Surveillance for asthma - United States, 1960-1995
5. Descriptive epidemiology of asthma
6. The costs of asthma
7. ERS consensus statement: Optimal assessment and management of chronic pulmonary disease
8. ATS: Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease
9. The impact of COPD on lung health Worldwide: Epidemiology and incidence
10. Mortality by cause for eight regions of the world: Global Burden of Disease Study
11. Evidence-based health-policy lessons from the Global Burden of Disease Study
12. Evaluation of current pharmacotherapy of chronic obstructive pulmonary disease
13. Pro/Con Editorial: Inhaled corticosteroids are/are not beneficial in chronic obstructive pulmonary disease
14. Anti-inflammatory and immunomodulatory potential of the novel PDE4 inhibitor roflumilast in vitro
15. In vivo efficacy in airway disease models of roflumilast, a novel orally-active PDE4 inhibitor
16. PDE inhibitors: Sustained patenting activity as leading drugs near the market
17. SB and Glaxo continue strong growth. Pharmaceuticals companies say merger is on track for completion by year-end
18. Ariflo
19. Phosphodiesterase isozymes: Molecular targets for novel antiasthma agents
20. Subtypes of the type 4 cAMP phosphodiesterases: Structure, regulation and selective inhibition
21. The multienzyme PDE4 cyclic adenosine monophosphate-specific phosphodiesterase family: Intracellular targeting, regulation, and selective inhibition by compounds exerting anti-inflammatory and antidepressant actions
22. Phosphodiesterase (PDE) 4 inhibitors: Drugs of the future?
23. Phosphodiesterase 4 inhibitors and the treatment of asthma: Where are we now and where do we go from here?
24. Cyclic AMP-dependent regulation of lipid mediators in white cells: A unifying concept for explaining the efficacy of theophylline in asthma
25. Proposal for pharmacologically distinct conformers of PDE4 cyclic AMP phosphodiesterases
26. Phosphodiesterase 4: Biological underpinnings of the design of improved inhibitors
27. PDE4 inhibitors: The use of molecular cloning in the design and development of novel drugs
28. The ability of phosphodiesterase IV inhibitors to suppress superoxide production in guinea pig eosinophils is correlated with inhibition of phosphodiesterase IV catalytic activity
29. Evidence that cyclic AMP phosphodiesterase inhibitors suppress interleukin-2 release from murine splenocytes by interacting with a 'low affinity' phosphodiesterase 4 conformer
30. 3H] rolipram binding
31. Evidence that cyclic AMP phosphodiesterase inhibitors suppress TNFα generation from human monocytes by interacting with a 'low-affinity' phosphodiesterase 4 conformer
32. 3H]rolipram binding activity and their relationship to emetic behavior in the ferret
33. Inhibitors of phosphodiesterase IV (PDE IV) increase acid secretion in rabbit isolated gastric glands: Correlation between function and interaction with a high-affinity rolipram binding site
34. 1,4-Cyclohexanecarboxylates: Potent and selective inhibitors of phosphodiesterase 4 for the treatment of asthma
35. Inhibition of cyclic adenosine-3′,5′-phosphate phosphodiesterase from vascular smooth muscle by rolipram analogues
36. PDE4 Inhibitors 1998
37. PDE4 inhibitors 1999
38. SB 207499, a potent and selective phosphodiesterase (PDE) IV inhibitor suppresses activities of several immune and inflammatory cells
39. Conformational difference between PDE4 apoenzyme and holoenzyme
40. Molecular basis for an improved therapeutic index of SB 207499, a second generation phosphodiesterase 4 inhibitor
41. Ariflo™ (SB 207499), a second generation phosphodiesterase 4 inhibitor for the treatment of asthma and COPD: From concept to clinic
42. Co-expression of human cAMP-specific phosphodiesterase activity and high affinity rolipram binding in yeast
43. SB 207499 (Ariflo), a potent and selective second-generation phosphodiesterase 4 inhibitor: In vitro anti-inflammatory actions
44. Ariflo, a novel and selective oral PDE4 inhibitor, has a favourable metabolic profile with low potential for drug-drug interactions
45. Ariflo, a novel and selective oral PDE4 inhibitor, has linear pharmacokinetics and high bioavailability
46. The pharmacokinetics of Ariflo (SB 207499), an orally-active novel and selective PDE4 inhibitor, are similar after morning and evening dosing
47. Ariflo (SB 207499), an orally active, second generation selective PDE4 inhibitor, does not interact with a variety of commonly administered COPD medications
48. An orally active, novel and selective PDE4 inhibitor, does not potentiate the anticoagulatory effect of warfarin in healthy male volunteers
49. Ariflo, (SB 207499), an orally-active, novel and selective PDE4 inhibitor, has no effect on the steady state pharmacokinetics of digoxin (375 mcg of) in healthy volunteers
50. The pharmacokinetics and tolerability profile of cilomilast (Ariflo), unaffected by co-administration of theophylline
51. The addition of SB 207499 (Ariflo), a novel and selective PDE4 inhibitor, to oral prednisolone, is safe and well tolerated
52. Cilomilast (Ariflo) 15 mg bid safety in a six month clinical trial program
53. Human liver microsomal cytochrome P-450 enzymes involved in the bioactivation of procarcinogens detected by emu gene response in Salmonella typhimurium TA 1535/pSK1002
54. A urinary metabolite ratio that reflects systemic caffeine clearance
55. Foreign compound metabolism capacity in man measured from metabolites of dietary caffeine
56. Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites
57. Biotransformation of caffeine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1
58. Biotransformation of caffeine and theophylline in mammalian cell lines genetically engineered for expression of single cytochrome P450 isoforms
59. Characterization of human liver cytochrome P-450 involved in theophylline metabolism
60. Theophylline metabolism in human liver microsomes: Inhibition studies
61. Metabolism of theophylline by cDNA-expressed human cytochromes P-450
62. Biotransformation of caffeine, paraxanthine, theophylline and theobromine by polycyclic aromatic hydrocarbon-inducible cytochrome P450 in human liver microsomes
63. Characterization of theophylline metabolism in human liver microsomes
64. Characterization of theophylline metabolism by human liver microsomes
65. Effect of smoking on theophylline disposition
66. The influence of cigarette smoking and sex on theophylline disposition
67. Theophylline disposition in acutely ill hospitalized patients. The effect of smoking, heart failure, severe airway obstruction, and pneumonia
68. Enhanced biotransformation of theophylline in marihuana and tobacco smokers
69. Influence of cigarette smoking on drug metabolism in man
70. Smoking status has no effect on the clearance of a single dose of Ariflo (SB 207499, 15 mg), an orally active, novel, second generation PDE4 inhibitor in healthy male volunteers
71. The safety and tolerability of Ariflo™ (SB 207499), a novel and selective phosphodiesterase 4 inhibitor, in healthy male volunteers
72. Ariflo™ improves pulmonary function in patients with asthma: Results of a study in patients taking inhaled corticosteroids
73. Safety of Ariflo in a 12-month study of patients with asthma
74. SB 207499 (Ariflo™), a second generation, selective oral phosphodiesterase *type 4 (PDE4) inhibitor, attenuates exercise-induced bronchoconstriction in patients with asthma
75. SB 207499 improves pulmonary function in patients with asthma receiving concomitant inhaled corticosteroids
76. Ariflo efficacy in a 12-month study of patients with asthma
77. The efficacy of Ariflo™ (SB 207499), a second generation, oral PDE4 inhibitor, in patients with COPD
78. SB 207499, second generation, oral PDE4 inhibitor, first demonstration of efficacy in patients with COPD
79. The effects of low-dose SB 207499, a second-generation, oral PDE4 inhibitor, in patients with COPD
80. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection
81. Ariflo (SB 207499), a second generation, oral PDE4 inhibitor, improves quality of life in patients with COPD
82. Cilomilast (Ariflo) a potent, selective phosphodiesterase 4 inhibitor, reduces exacerbations in COPD patients: Results of a 6 month trial
83. Cilomilast (Ariflo), a potent, selective inhibitor of phosphodiesterase 4, improves lung function in patients with COPD: Results of a 6-month trial
84. Cilomilast (Ariflo) improves health status in patients with COPD: Results of a 6 month trial
85. The safety of cilomilast (Ariflo) co-administration with oral theophylline: Cardiovascular profile
86. The economic burden of COPD
87. Cilomilast reduces healthcare resource utilization of chronic obstructive pulmonary disease patients
88. Phosphodiesterase 4B2 is the predominant phosphodiesterase species and undergoes differential regulation of gene expression in human monocytes and neutrophils
89. Suppression of human inflammatory cell function by subtype-selective PDE4 inhibitors correlates with inhibition of PDE4A and PDE4B
90. Absence of muscarinic cholinergic airway responses in mice deficient in the cyclic nucleotide phosphodiesterase PDE4D
91. 2 and cAMP-elevating drugs on GM-CSF release by human airway smooth muscle
92. Tumor necrosis factor-α-induced secretion of RANTES and interleukin-6 from human airway smooth muscle cells. Modulation by cyclic adenosine monophosphate
93. CRE, but not AP-1, NF-κB or C/EBP, mediates cAMP-induced IL-6 gene expression in human airway smooth muscle cells
94. Ariflo (SB 207499) modulates human airway smooth muscle. Cell proliferation induced by mitogens
95. Ariflo (SB 207499), a selective phosphodiesterase (PDE) 4 inhibitor, inhibits human airway smooth muscle (HASM) cell proliferation induced by mitogens
96. Antiasthmatic activity of the second-generation phosphodiesterase 4 (PDE4) inhibitor SB 207499 (Ariflo) in the guinea pig
97. Ariflo (SB 207499), a selective phosphodiesterase (PDE) 4 inhibitor, modulates neuronal responses in guinea-pig and human airway in vitro
98. Cilomilast (Ariflo) reduces TNFα and GM-CSF release by airway cells isolated from COPD patients
99. Effect of PDE4 inhibitors on zymosan-induced IL-8 release from human neutrophils: Synergism with prostanoids and salbutamol
100. Selective inhibition of neutrophil function by the phosphodiesterase 4 inhibitor SB 207499
101. Cilomilast (Ariflo) inhibits neutrophil pro-inflammatory activities
102. PDE4 inhibitors attenuate fibroblast chemotaxis and contraction of native collagen gels: Potential antifibrotic effects
103. The phosphodiesterase IV inhibitor SB 207499 inhibits cytokine and elastase induced fibroblast degradation of three dimensional collagen gels
104. Inhibition of LPS-induced pulmonary inflammation by beclomethasone and SB 207499 in rats
105. Efficacy of the selective phosphodiesterase (PDE) 4 inhibitor, BAY 19-8004, in a rat model of neutrophilic lung inflammation
106. Influence of the selective phosphodiesterase (PDE) 4 inhibitor, Ariflo (SB 207499), on expression of mucin (MUC) gene 5AC in airways of allergic Brown-Norway (BN) rats
107. Anti-inflammatory effect of selective PDE inhibitors on ear inflammation in Swiss mice
108. A comparison of the effect of PDE4 inhibitors on neutrophilia and cytokine expression in a murine model of LPS-induced lung inflammation
109. SB 207499 (Ariflo), a second generation phosphodiesterase 4 inhibitor, reduces tumor necrosis factor alpha and interleukin-4 production in vivo
110. Effect of cilomilast, an orally-active, selective PDE4 inhibitor in a murine viral/bacterial co-infection model
111. Effect of a selective PDE4 inhibitor, SB 207499, on airway cough hypersensitivity induced by allergic eosinophilic bronchitis
112. Correlation of inhaled antigen- or cysteinyl leukotriene-induced hypertussive activity with airway eosinophilia in guinea-pigs
113. Ariflo (SB 207499) inhibits airway neutrophilia, inflammatory cytokine production and matrix metalloproteinase-9 activity in the guinea-pig
114. Effects of a selective PDE4 inhibitor, D-22888, on human airways and eosinophils in vitro and late phase allergic pulmonary eosinophilia in guinea pigs
115. The therapeutic activity of SB 207499 (Ariflo), a second generation phosphodiesterase 4 (PDE4) inhibitor, is equivalent to that of prednisolone in models of pulmonary inflammation
116. 4-induced mobilization of peripheral blood neutrophils in rabbits
117. The selective phosphodiesterase 4 inhibitor CI-1044 (PD189659) inhibits LPS-induced neutrophil recruitment and TNFα release in rat airways
118. Effects of s selective PDE4 inhibitor AWD 12-281 in comparison with SB 207499 and roflumilast on tracheal phenol red secretion in mice and LPS-induced neutrophilia in Lewis rats and domestic pigs
119. Effect of the phosphodiesterase (PDE4) inhibitor Ariflo on polymorphonuclear leukocyte (PMN) trapping in rabbit pulmonary circulation
120. Effects of selective phosphodiesterase 4 inhibitors on functional responses of human neutrophils and eosinophils