Safety, pharmacodynamics and pharmacokinetics of TPI 1020 in smokers with asthma

Respiratory Medicine

Volumn 103, Issue 8, 2009, Pages 1159-1166

  Boulet, Louis Philippe ^a   Lemière, Catherine ^b   Gauvreau, Gail ^c   Olivenstein, Ron ^d   Lougheed, Diane ^e   Paradis, Bruno ^f   O'Byrne, Paul ^c   Pageau, René ^g   Renzi, Paolo M ^g,h  

^a LAVAL UNIVERSITY   (Canada)

^b HÔPITAL DU SACRÉ COEUR DE MONTRÉAL   (Canada)

^c MCMASTER UNIVERSITY   (Canada)

^d MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

^e KINGSTON GENERAL HOSPITAL   (Canada)

^f JEWISH REHABILITATION HOSPITAL   (Canada)

^g Topigen Pharmaceuticals   (Canada)

^h UNIVERSITÉ DE MONTRÉAL   (Canada)

Author keywords

Airway inflammation; Asthma drug therapy; Neutrophils; Nitric oxide

Indexed keywords

ANTIINFLAMMATORY AGENT; BUDESONIDE; C REACTIVE PROTEIN; HYDROCORTISONE; METHACHOLINE; NITRIC OXIDE; TPI 1020; UNCLASSIFIED DRUG;

ADULT; ARTICLE; ASTHMA; CIGARETTE SMOKING; CLINICAL ARTICLE; CLINICAL TRIAL; CONJUNCTIVITIS; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG DELIVERY SYSTEM; DRUG DOSE ESCALATION; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; DYSPNEA; EAR DISEASE; FEMALE; FORCED EXPIRATORY VOLUME; HEADACHE; HUMAN; INSOMNIA; LYMPHADENOPATHY; MALE; MAXIMUM PLASMA CONCENTRATION; MULTICENTER STUDY; MUSCLE SPASM; NEUTROPHIL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SPUTUM ANALYSIS; THORAX PAIN; UNSPECIFIED SIDE EFFECT; UPPER ABDOMINAL PAIN; UREA NITROGEN BLOOD LEVEL; URINARY TRACT INFECTION; URINE LEVEL;

ADOLESCENT; ADULT; AGED; ANTI-INFLAMMATORY AGENTS; ASTHMA; BUDESONIDE; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; FORCED EXPIRATORY VOLUME; HUMANS; MALE; MIDDLE AGED; NEUTROPHIL ACTIVATION; NITRIC OXIDE; SPUTUM; TREATMENT OUTCOME; YOUNG ADULT;

EID: 67649090223     PISSN: 09546111     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.rmed.2009.02.011     Document Type: Article

References (28)

1. Barnes P.J. New therapies for asthma. Trends Mol Med 12 (2006) 515-520
2. Massaro A.F., Gaston B., Kita D., Fanta C., Stamler J.S., and Drazen J.M. Expired nitric oxide levels during treatment of acute asthma. Am J Respir Crit Care Med 152 (1995) 800-803
3. Smith A.D., Cowan J.O., Brassett K.P., Filsell S., McLachlan C., Monti-Sheehan G., et al. Exhaled Nitric oxide. A predictor of steroid response. Am J Respir Crit Care Med 172 (2005) 453-459
4. Kebir D.E., Hubert B., Taha R., Troncy E., Wang T., Gauvin D., et al. Effects of inhaled nitric oxide on inflammation and apoptosis after cardiopulmonary bypass. Chest 128 (2005) 2910-2917
5. Kacmarek R.M., Ripple R., Cockrill B.A., Bloch K.J., Zapol W.M., and Johnson D.C. Inhaled nitric oxide. A bronchodilator in mild asthmatics with methacholine-induced bronchospasm. Am J Respir Crit Care Med 153 (1996) 128-135
6. Högman M., Frostell C.G., Hedenström H., and Hedenstierna G. Inhalation of nitric oxide modulates adult human bronchial tone. Am Rev Respir Dis 148 (1993) 1474-1478
7. Tallet D., Del Soldato P., Oudart N., and Burgaud J.L. No-steroids:anti-inflammatory drugs with bronchodilating activity in vitro. Biochem Biophys Res Commun 290 (2002) 125-130
8. Nevin B.J., and Broadley K.J. Comparative effects of inhaled budesonide and the no-donating budesonide derivative, NCX 1020, against leukocyte influx and airway hyperreactivity following lipopolysaccharide challenge. Pulm Pharmacol Therapeut 17 (2004) 219-232
9. Chaudhuri R., Livingston E., McMahon A.D., Lafferty J., Fraser I., Spears M., et al. Effects of smoking cessation on lung function and airway inflammation in smokers with asthma. Am J Respir Crit Care Med 174 (2006) 127-133
10. Pellegrino R., Viegi G., Brusasco V., Crapo R.O., Burgos F., Casaburi R., et al. Interpretative strategies for lung function tests. Eur Respir J 26 (2005) 948-968
11. LeBlanc A., Robichaud P., Lacasse Y., and Boulet L.P. Quantification of asthma control: validation of the Asthma Control Scoring System. Allergy 62 (2007) 120-125
12. Pizzichini E., Pizzichini M.M., Efthimiadis A., Evans S., Morris M.M., Squillace D., et al. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med 154 (1996) 308-317
13. Cockcroft D.W. Methacholine challenge. In: Hargreave F.E., and Woolcock A.J. (Eds). Measurement and interpretation (1985), Astra Pharmaceuticals, Mississauga, ON 22-28
14. Gamble E., Grootendorst D.C., Brightling C.E., Troy S., Qiu Y., Zhu J., et al. Antiinflammatory effects of the phosphodiesterase-4 inhibitor cilomilast (Ariflo) in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 168 (2003) 976-982
15. Turner S. The role of exhaled nitric oxide in the diagnosis, management and treatment of asthma. Mini Rev Med Chem 7 (2007) 539-542
16. Duong M., Gauvreau G., Watson R., et al. The effects of inhaled budesonide and formoterol in combination and alone when given directly after allergen challenge. J Allergy Clin Immunol 119 (2007) 322-327
17. Weiling X., Zheng S., Dweik A., and Erzurum S.C. Role of epithelial nitric oxide in airway viral infection. Free Radic Biol Med 41 (2006) 19-28
18. Fang F.C. Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nat Rev Microbiol 2 (2004) 820-832
19. Fang F.C. Mechanisms of nitric ocide-related antimicrobial activity. J Clin Invest 99 (1997) 2818-2825
20. Broeke R.T., De Crom R., Van Haperen V., Verweij V., Leusink-Muis T.A., Van Ark I., et al. Overexpression of endothelial nitric oxide synthase suppresses features of allergic asthma in mice. Respir Res (serial on line) 7 (2006) 58. http://respiratory-research.com/content/7/1/58 Available from
21. Tattersfield A.E., Harrison T.W., Hubbard R.B., and Mortimer K. Safety of inhaled corticosteroids. Proc Am Thorac Soc 1 (2004) 171-175
22. U.S. National Institutes of Health. National Heart, Lung and Blood Institute. Guidelines for the diagnosis and management of asthma. NIH Publication 97:4051:1-153.
23. Masoli M., Holt S., Weatherhall M., and Beasley R. Dose-response relationship of inhaled budesonide in adult asthma: a meta-analysis. Eur. Respir J (2004) 552-559
24. Lemière C., Bai T., Balter M., Bayliff C., Becker A., Boulet L.P., et al. Adult asthma consensus guidelines update 2003. Can Respir J 11 (2004) 5A-33A
25. Bernstein D.I., and Allen D.B. Evaluation of tests of hypothalamic-pituitary-adrenal axis function used to measure effects of inhaled corticosteroids. Ann Allergy Asthma Immunol 98 (2007) 118-127
26. Lazarus S.C., Chinchilli V.M., Rollings N.J., Boushey H.A., Cherniack R., Craig T.J., et al. Smoking affects response to inhaled corticosteroids or leukotriene receptor antagonists in asthma. Am J Respir Critic Care Med 175 (2007) 783-790
27. Dahl M., Vestbo J., Lange P., Bojesen S.E., Tybjaerg-Hansen A., and Nordestgaard B.G. C-reactive protein as a predictor of prognosis in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 175 (2007) 250-255
28. Anderson G.P. COPD, asthma and C-reactive protein. Eur Respir J 27 (2006) 874-876