RT Journal Article
SR Electronic
T1 Combination study of tiotropium and olodaterol in human precision-cut lung slices
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P1588
VO 42
IS Suppl 57
A1 Marco Schlepütz
A1 Nina Maihöfer
A1 Annette D. Rieg
A1 Saskia Westphal
A1 Alberto Perez-Bouza
A1 Till Braunschweig
A1 Thomas Schröder
A1 Jan W. Spillner
A1 Rüdiger Autschbach
A1 Michael P. Pieper
A1 Stefan Uhlig
A1 Christian Martin
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P1588.abstract
AB In COPD, monotherapy often fails to improve health status. Hence, combinations of bronchodilators are recommended. The pharmacological impact of drugs on bronchoconstriction (BC) can be determined in vitro by precision-cut lung slices (PCLS). So, the present aim was to characterize the combined effect of tiotropium and the novel LABA olodaterol on BC in human lung tissue.PCLS were prepared from lung lobes received from cancer patients. BC in PCLS was monitored by videomicroscopy. First, concentration-response curves with carbachol (CCh, 10-8–10-3M) were performed in the presence and absence of tiotropium (10-11-10-8M) or olodaterol (10-10–10-7M). For the combined effect of tiotropium and olodaterol, concentration-response curves with CCh were conducted at 10-9.5M tiotropium or 10-9M olodaterol alone and in their combination.Tiotropium concentration-dependently inhibited CCh-induced BC and a suitable inhibitory concentration for the combination study was found at 10-9.5M. The functional antagonist olodaterol also inhibited CCh-induced BC and an appropriate inhibitory concentration for the combination study was determined to 10-9M. In the combination study half-maximal effective concentrations (logEC50) for CCh-induced BC were -5.9±0.2 under control conditions, -5.7±0.1 at 10-9.5M tiotropium, -5.4±0.2 at 10-9M olodaterol and -4.6±0.2 for the combination of tiotropium and olodaterol.In vitro the combination of tiotropium and olodaterol was more effective to inhibit BC than each bronchodilator alone. Since those studies were performed in human tissue, correlation to the in vivo situation may be allowed and the combination of tiotropium and olodaterol may be beneficial in the treatment of patients.