The pharmacokinetics and pharmacodynamics of danirixin (GSK1325756) - a selective CXCR2 antagonist - in healthy adult subjects

BMC Pharmacology and Toxicology

Volumn 16, Issue 1, 2015, Pages

  Miller, Bruce E ^a   Mistry, Sunil ^b   Smart, Kevin ^b,c   Connolly, Paul ^b   Carpenter, Donald C ^a   Cooray, Hiran ^b,d   Bloomer, Jackie C ^b   Tal Singer, Ruth ^a   Lazaar, Aili L ^a  

^a GLAXOSMITHKLINE   (United States)

^b GLAXOSMITHKLINE   (United Kingdom)

^c ROCHE PRODUCTS LTD   (United Kingdom)

^d AMGEN INC   (United States)

Author keywords

Chronic obstructive pulmonary disease; CXCR2 antagonist; Danirixin; GSK1325756; Omeprazole; Pharmacodynamics; Pharmacokinetics

Indexed keywords

DANIRIXIN; OMEPRAZOLE; PLACEBO; CD11B ANTIGEN; CHEMOKINE RECEPTOR CXCR2; CXCL1 CHEMOKINE; ITGAM PROTEIN, HUMAN; NONSTEROID ANTIINFLAMMATORY AGENT; PIPERIDINE DERIVATIVE; SULFONE;

ABDOMINAL PAIN; ADULT; AGE; AGED; APPLICATION SITE RASH; AREA UNDER THE CURVE; ARTICLE; ATOPIC DERMATITIS; BACKACHE; BLEEDING; COMPARATIVE EFFECTIVENESS; CONTROLLED STUDY; DISEASE SEVERITY; DIZZINESS; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG ANTAGONISM; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG HALF LIFE; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPEPSIA; FEMALE; FOOD DRUG INTERACTION; FOOD INTAKE; HEADACHE; HOT FLUSH; HUMAN; HUMAN EXPERIMENT; INFUSION RELATED REACTION; LEUKOCYTE ACTIVATION; MALE; MAXIMUM PLASMA CONCENTRATION; NAUSEA; NORMAL HUMAN; PHARMACODYNAMICS; RANDOMIZED CONTROLLED TRIAL; REPEATED DRUG DOSE; RHINOPHARYNGITIS; SEX DIFFERENCE; SINGLE DRUG DOSE; SINUSITIS; SOMNOLENCE; TIME TO MAXIMUM PLASMA CONCENTRATION; VIRAL GASTROENTERITIS; ADOLESCENT; ADVERSE EFFECTS; ANTAGONISTS AND INHIBITORS; BLOOD; DRUG EFFECTS; FOOD; METABOLISM; MIDDLE AGED; NEUTROPHIL; YOUNG ADULT;

ADOLESCENT; ADULT; AGE FACTORS; AGED; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ANTIGENS, CD11B; CHEMOKINE CXCL1; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FOOD; HEALTHY VOLUNTEERS; HUMANS; MALE; MIDDLE AGED; NEUTROPHILS; OMEPRAZOLE; PIPERIDINES; RECEPTORS, INTERLEUKIN-8B; SULFONES; YOUNG ADULT;

EID: 84934979596     PISSN: 20506511     EISSN: 20506511     Source Type: Journal    
DOI: 10.1186/s40360-015-0017-x     Document Type: Article

References (15)

1. Scholten DJ, Canals M, Maussang D, Roumen L, Smit MJ, Wijtmans M, et al. Pharmacological modulation of chemokine receptor function. Br J Pharmacol. 2012;165:1617-43.
2. Chapman RW, Phillips JE, Hipkin RW, Curran AK, Lundell D, Fine JS. CXCR2 antagonists for the treatment of pulmonary disease. Pharmacol Ther. 2009;121:55-68.
3. Caramor G, Di Stefano A, Casolari P, Kirkham PA, Padovani A, Chung KF, et al. Chemokines and chemokine receptors blockers as new drugs for the treatment of chronic obstructive pulmonary disease. Curr Med Chem. 2013;20:4317-49.
4. Lazaar AL, Sweeney LE, MacDonald AJ, Alexis NE, Chen C, Tal-Singer R. SB-656933, a novel CXCR2 selective antagonist, inhibits ex vivo neutrophil activation and ozone-induced airway inflammation in humans. Br J Clin Pharmacol. 2011;72:282-93.
5. Holz O, Khalilieh S, Ludwig-Senqpiel A, Watz H, Stryszak P, Soni P, et al. SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects. Eur Respir J. 2010;35:564-70.
6. Todd CM, Murphy DM, Watson RM, Howie K, Strinich TX, Penk K, et al. Treatment with the CXCR2 antagonist SCH527123 reduced neutrophil levels in blood and airways but not bone marrow in mild asthmatic subjects. Am J Respir Crit Care Med. 2010;181:A4237.
7. Nair P, Gaga M, Zervas E, Alagha K, Hargreave FE, O'Byrne PM, et al. Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils: a randomized, placebo-controlled clinical trial. Clin Exp Allergy. 2012;42:1097-103.
8. Magnussen H, Holz O, Watz H, Sauer M, Khanskaya I, Gann L, et al. Safety and efficacy of SCH527123, a novel CXCR2 antagonist, in patients with COPD. Eur Respir J 2010;36(Suppl 54):38S
9. Spooner N, Lad R, Barfield M. Dried blood spots as a sample collection technique for the determination of pharmacokinetics in clinical studies: considerations for the validation of a quantitative bioanalytical method. Anal Chem. 2009;81:1557-63.
10. Nicholson GC, Tennant RC, Carpenter DC, Sarau HM, Kon OM, Barnes PJ, et al. A novel flow cytometric assay of human whole blood neutrophil and monocyte CD11b levels: upregulation by chemokines is related to receptor expression, comparison with neutrophil shape change, and effects of a chemokine receptor (CXCR2) antagonist. Pulm Pharmacol Ther. 2007;20:52-9.
11. Rodriguez G, Ruigómez A, Martin-Merion E, Johannson S, Wallander MA. Relationship between gastroesophageal reflux disease and COPD in UK primary care. Chest. 2008;134:1223-30.
12. Kempainen RR, Savik K, Whelan TP, Dunitz JM, Herrington CS, Billings JL. High prevalence of proximal and distal gastroesophageal reflux disease in advanced COPD. Chest. 2007;131:1666-71.
13. Casanova C, Baudet JS, del Valle Velasco M, et al. Increased gastro-oesophageal reflux disease in patients with severe COPD. Eur Respir J. 2004;23:841-5.
14. Blum RA, Shi H, Karol MD, Greski-Rose PA, Hunt RH. The comparative effects of lansoprazole, omeprazole, and ranitidine in suppressing gastric acid secretion. Clin Ther. 1997;19:1013-23.
15. Bloomer JC, Nash M, Webb A, Miller BE, Lazaar AL, Beaumont C, et al. Assessment of potential drug interactions by characterization of human drug metabolism pathways using non-invasive bile sampling. Br J Clin Pharmacol. 2013;75:488-96.