TY - JOUR
T1 - A randomized, placebo-controlled study of the effects of the p38 MAPK inhibitor SB-681323 on blood biomarkers of inflammation in COPD patients
AU - Singh, Dave
AU - Smyth, Lucy
AU - Borrill, Zoe
AU - Sweeney, Lisa
AU - Tal-Singer, Ruth
PY - 2010/1
Y1 - 2010/1
N2 - The p38 mitogen-activated protein kinase (MAPK) signaling upregulates inflammation and is known to be increased in chronic obstructive pulmonary disease (COPD). The authors assessed the pharmacology of the novel p38 MAPK inhibitor SB-681323 using blood biomarkers in COPD. Seventeen COPD patients (forced expiratory volume in 1 second 50%-80% predicted) using short-acting bronchodilators participated in a double-blind, double-dummy, randomized, crossover study. Patients received single oral doses of SB-681323 7.5 mg and 25 mg, prednisolone 10 mg and 30 mg, and placebo. Blood was obtained predose and at 1, 2, 6, and 24 hours postdose. Whole-blood sorbitol-induced phosphorylated (p) heat shock protein (HSP) 27 levels as a marker of p38 pathway activation and lipopolysaccharide-induced tumor necrosis factor (TNF)-α production were assessed. Both doses of SB-681323, but not prednisolone, significantly (P
AB - The p38 mitogen-activated protein kinase (MAPK) signaling upregulates inflammation and is known to be increased in chronic obstructive pulmonary disease (COPD). The authors assessed the pharmacology of the novel p38 MAPK inhibitor SB-681323 using blood biomarkers in COPD. Seventeen COPD patients (forced expiratory volume in 1 second 50%-80% predicted) using short-acting bronchodilators participated in a double-blind, double-dummy, randomized, crossover study. Patients received single oral doses of SB-681323 7.5 mg and 25 mg, prednisolone 10 mg and 30 mg, and placebo. Blood was obtained predose and at 1, 2, 6, and 24 hours postdose. Whole-blood sorbitol-induced phosphorylated (p) heat shock protein (HSP) 27 levels as a marker of p38 pathway activation and lipopolysaccharide-induced tumor necrosis factor (TNF)-α production were assessed. Both doses of SB-681323, but not prednisolone, significantly (P
KW - Chronic obstructive pulmonary disease
KW - Corticosteroids
KW - P38 kinase
U2 - 10.1177/0091270009347873
DO - 10.1177/0091270009347873
M3 - Article
C2 - 19880675
SN - 0091-2700
VL - 50
SP - 94
EP - 100
JO - Journal of Clinical Pharmacology
JF - Journal of Clinical Pharmacology
IS - 1
ER -
