Tolerability and pharmacokinetics of inhaled bimosiamose disodium in healthy males

British Journal of Clinical Pharmacology

Volumn 63, Issue 4, 2007, Pages 451-458

  Meyer, Michael ^a   Beeh, Kai Michael ^b   Beier, Jutta ^b   Beyer, Diana ^a   Aydt, Ewald ^a   Zahlten, Rainer ^a   Jilma, Bernd ^c   Wolff, Gerhard ^a  

^a Revotar Biopharmaceuticals AG   (Germany)

^b Institut fur Atemwegsforschung INSAF   (Germany)

^c MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

Bimosiamose; Inhalation; Pharmacokinetics; Phase I trial; Safety and tolerability; Selectin

Indexed keywords

BIMOSIAMOSE; PLACEBO;

ADULT; ANKLE DISLOCATION; AREA UNDER THE CURVE; ARTICLE; BLOOD SAMPLING; CLINICAL TRIAL; COATED TONGUE; CONJUNCTIVA DISEASE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG EFFECT; DRUG EFFICACY; DRUG FORMULATION; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERABILITY; DRY SKIN; DYSPNEA; ELECTROCARDIOGRAM; ERYTHEMA; FLATULENCE; FLU LIKE SYNDROME; FORCED EXPIRATORY VOLUME; HEART PALPITATION; HEARTBURN; HERPES ZOSTER; HUMAN; INJECTION SITE PAIN; LABORATORY TEST; LOOSE FECES; MALE; NEBULIZER; NECK PAIN; NORMAL HUMAN; PAPULAR RASH; PHYSICAL EXAMINATION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINITIS; SALIVATION; SIDE EFFECT; SINGLE DRUG DOSE; SORE THROAT; THORAX PAIN; VASCULAR DISEASE; VITAL SIGN; XEROSTOMIA;

ADMINISTRATION, INHALATION; ADULT; CELL ADHESION; HEXANES; HUMANS; MALE; MANNOSE; MIDDLE AGED; NASOPHARYNGEAL DISEASES;

EID: 33947286765     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2006.02775.x     Document Type: Article

References (31)

1. Paron P, Worthen GS, Henson PM. Injury from inflammatory cells. In: The Lung Scientific Foundation, edition 2nd edn, eds Crystal RG, West JB, Weibel ER, Barnes PJ, Philadelphia, PA: Lippinscott-Raven 1997: 2439-49.
2. Weber C. Novel mechanistic concepts for the control of leukocyte transmigration: specialization of integrins, chemokines, and junctional molecules. J Mol Med 2003; 81: 4-19.
3. Ridings PC, Holloway S, Bloomfield GL, Phillips ML, Fisher BJ, Blocher CR, Sugerman HJ, Fowler AA. Protective role of synthetic sialylated oligosaccharide in sepsis-induced acute lung injury. J Appl Physiol 1997; 82: 644-51.
4. Romano SJ, Slee DH. Targeting selectins for the treatment of respiratory diseases. Curr Opin Invest Drugs 2001; 2: 907-13.
5. Aydt EM, Wolff G. Development of synthetic pan-selectin antagonists: a new treatment strategy for chronic inflammation in asthma. Pathobiology 2002; 70: 297-301.
6. Gauvreau GM, Becker AB, Boulet LP, Chakir J, Fick RB, Greene WL, Killian KJ, O'Byrne PM, Reid JK, Cockcroft DW. The effects of an anti-CD11a mAb, efalizumab, on allergen-induced airway responses and airway inflammation in subjects with atopic asthma. J Allergy Clin Immunol 2003; 112: 331-8.
7. Magnani JL. The discovery, biology, and drug development of sialyl Lea and sialyl Lex. Arch Biochem Biophys 2004; 426: 122-31.
8. Vanderslice P, Biediger RJ, Woodside DG, Berens KL, Holland GW, Dixon RA. Development of cell adhesion molecule antagonists as therapeutics for asthma and COPD. Pulm Pharmacol Ther 2004; 17: 1-10.
9. Romano SJ. Selectin antagonists - therapeutic potential in asthma and COPD. Treat Respir Med 2005; 4: 85-94.
10. Kansas GS. Selectins and their ligands: current concepts and controversies. Blood 1996; 88: 3259-87.
11. Schön MP, Krahn T, Schön M, Rodriguez ML, Antonicek H, Schultz JE, Ludwig RJ, Zollner TM, Bischoff E, Bremm KD, Schramm M, Henninger K, Kaufmann R, Gollnick HP, Parker CM, Boehncke W-H. Efomycine M, a new specific inhibitor of selectin, impairs leukocyte adhesion and alleviates cutaneous inflammation. Nat Med 2002; 8: 366-72.
12. Kogan TP, Dupre B, Bui H, McAbee KL, Kassir JM, Scott IL, Hu X, Vanderslice P, Beck PJ, Dixon RA. Novel synthetic inhibitors of selectin-mediated cell adhesion: synthesis of 1,6-bis[3-(3-carboxymethylphenyl)- 4-(2-alpha-D- mannopyranosyloxy) phenyl] hexane (TBC1269). J Med Chem 1998; 41: 1099-111.
13. Davenpeck KL, Berens KL, Dixon RA, Dupre B, Bochner BS. Inhibition of adhesion of human neutrophils and eosinophils to P-selectin by the sialyl Lewis antagonist TBC1269: preferential activity against neutrophil adhesion in vitro. J Allergy Clin Immunol 2000; 105: 769-75.
14. Palma-Vargas JM, Toledo-Pereyra L, Dean RE, Harkema JM, Dixon RA, Kogan TP. Small-molecule selectin inhibitor protects against liver inflammatory response after ischemia and reperfusion. J Am Coll Surg 1997; 185: 365-72.
15. Abraham WM, Ahmed A, Sabater JR, Lauredo IT, Botvinnikova Y, Bjercke RJ, Hu X, Revelle BM, Kogan TP, Scott IL, Dixon RA, Yeh ET, Beck PJ. Selectin blockade prevents antigen-induced late bronchial responses and airway hyperresponsiveness in allergic sheep. Am J Respir Crit Care Med 1999; 159: 1205-14.
16. Ramos-Kelly JR, Toledo-Pereyra LH, Jordan JA, Rivera-Chavez FA, Dixon RA, Ward PA. Upregulation of lung chemokines associated with hemorrhage is reversed with a small molecule multiple selectin inhibitor. J Am Coll Surg 1999; 189: 546-53.
17. Radi ZA, Brogden KA, Dixon RA, Gallup JM, Ackermann MR. A selectin inhibitor decreases neutrophil infiltration during acute Mannheimia haemolytica pneumonia. Vet Pathol 2002; 39: 697-705.
18. Anaya-Prado R, Ramos-Kelly JR, Toledo-Pereyra LH, Walsh J, Ward PA. Multiple selectin blockade with a small-molecule selectin inhibitor does not affect survival after a second inflammatory challenge with nonlethal LPS. J Invest Surg 2002; 15: 171-80.
19. Meyer M, Jilma B, Zahlten R, Wolf G. Physicochemical properties, safety and pharmacokinetics of bimosiamose disodium for intravenous administration. Int J Clin Pharmacol Ther 2005; 43: 463-71.
20. Beeh KM, Beier J, Meyer M, Buhl R, Zahlten R, Wolff G. Bimosiamose, an inhaled small-molecule pan-selectin antagonist, attenuates late asthmatic reactions following allergen challenge in mild asthmatics. Pulm Pharmacol Ther 2006; 19: 233-41.
21. Papac DI, Shahrokh Z. Mass spectrometry innovations in drug discovery and development. Pharm Res 2001; 18: 131-45.
22. Aydt EM, Vigano M, Meyer M, Böttcher K. Data management and data mining in biotech companies - an integrated appoach. In: Designing Drug and Crop Protectants: Processes, Problems and Solutions, eds Ford M, Livingstone D, Dearden J, van de Waterbeemd H. Malden: Blackwell Publishing Ltd 2003: 408-13.
23. R Development Core Team. R: A Language and Environment for Statistical Computing. Vienna: R Foundation for Statistical Computing 2004. Available at http://www.R-project.org (last accessed: 31 March 2005).
24. Anonymus. Determinants of bronchial responsiveness in the European Community Respiratory Health Survey in Italy: evidence of a independent role of atopy, total serum IgE levels, and asthma symptoms. Allergy 1998; 53: 668-73.
25. Laprise C, Boulet LP. Asymptomatic airway hyperresponsiveness: a three-year follow-up. Am J Respir Crit Care Med 1997; 156: 403-9.
26. Katz SL, Ho SL, Coates AL. Nebulizer choice for inhaled colistin treatment in cystic fibrosis. Chest 2001; 119: 250-5.
27. Barry PW, O'Callaghan C. An in vitro analysis of the output of budesonide from different nebulizers. J Allergy Clin Immunol 1999; 104: 1168-73.
28. Barry PW, O'Callaghan C. An in vitro analysis of the output of salbutamol from different nebulizers. Eur Respir J 1999; 13: 1164-9.
29. Wildhaber JH, Dore ND, Wilson JM, Devadason SG, LeSoeuf PN. Inhalation therapy in asthma: nebulizer or pressurized metered dose inhaler with holding chamber? In vivo comparison of lung deposition in children. J Pediatr 1999; 135: 28-33.
30. Sears MR. Adverse effects of beta-agonists. J Allergy Clin Immunol 2002; 110: S322-S328.
31. Roth AP, Lange CF, Finlay WH. The effect of breathing pattern on nebulizer drug delivery. J Aerosol Med 2003; 16: 325-39.