Journal: The Journal of Biological Chemistry

Article Title: Identification and analyses of inhibitors targeting apolipoprotein(a) kringle domains KIV-7, KIV-10, and KV provide insight into kringle domain function

doi: 10.1074/jbc.RA119.011251

Figure Lengend Snippet: Inhibitory effect of kringle-specific compounds on apo(a) binding to fibrin and apo(a)-induced Lp(a) assembly measured by SPR. Inhibitory effect of compounds AZ-05KIV-10 (red squares), AZ-06KIV-7 (blue circles), and TX (black crosses) on association between fl_apo(a) in solution and immobilized fibrin (A) or immobilized native LDL particles (B). A combination experiment was performed where equal concentrations of AZ-05KIV-10 and AZ-06KIV-7 were co-titrated (green diamonds), and the concentration of each separate compound is indicated on the x axis. The points represent an average from three experiments, and the bars represent the standard deviation. A, inhibition of apo(a) binding to fibrin was performed at a fl_apo(a) concentration of 9.6 nm. The same SPR chip was used for all data points, except the reference titration of TX, and the surfaces were regenerated between injections. The dose-response curve of TX inhibition of the fl_apo(a)–fibrin interaction gave an apparent Ki of 30 μm. B, Lp(a) assembly was studied by adding fl_apo(a) in solution to native LDL particles immobilized on the SPR sensor chip. The fl_apo(a) concentration was 100 nm. The same chip was used for all data points, except the reference titration of TX, and the surface was regenerated by injection of 10 mm TX. The dose response of TX inhibition of the fl_apo(a)–LDL interaction (Lp(a) assembly) gave an apparent Ki of 30 μm.

Article Snippet: Lp(a) assembly SPR assay Biotinylated native LDL (Biotrend) at 5 μg/ml was coupled to streptavidin on the sample channel of an SA-chip sensor surface (GE Healthcare) in 10 m m HEPES, pH 7.4, 0.15 m NaCl, 0.05% (v/v) polysorbate 20, 3 m m EDTA, 10 μ m butylated hydroxytoluene (BHT) using the immobilization wizard in the Biacore T200 software (GE Healthcare).

Techniques: Binding Assay, Concentration Assay, Standard Deviation, Inhibition, Titration, Injection

Journal: BMC Clinical Pharmacology

Article Title: No relevant cardiac, pharmacokinetic or safety interactions between roflumilast and inhaled formoterol in healthy subjects: an open-label, randomised, actively controlled study

doi: 10.1186/1472-6904-11-7

Figure Lengend Snippet: Time course of the geometric mean (68% range) plasma concentrations of roflumilast (linear scale) . R alone: roflumilast 500 μg once daily at steady state (Regimen A: Day 11; n = 12); RF: roflumilast 500 μg once daily and formoterol 24 μg twice daily at steady state (Regimen A: Day 18; n = 12); FR: formoterol 24 μg twice daily and roflumilast 500 μg once daily at steady state (Regimen B: Day 18; n = 12).

Article Snippet: Determination of roflumilast and roflumilast N-oxide was performed at Altana Pharma AG, Konstanz, Germany (Nycomed GmbH).

Techniques: Clinical Proteomics

Journal: BMC Clinical Pharmacology

Article Title: No relevant cardiac, pharmacokinetic or safety interactions between roflumilast and inhaled formoterol in healthy subjects: an open-label, randomised, actively controlled study

doi: 10.1186/1472-6904-11-7

Figure Lengend Snippet: Geometric means (68% inter-percentile range) of the main pharmacokinetic variables for roflumilast and roflumilast N-oxide at steady state

Article Snippet: Determination of roflumilast and roflumilast N-oxide was performed at Altana Pharma AG, Konstanz, Germany (Nycomed GmbH).

Techniques:

Journal: BMC Clinical Pharmacology

Article Title: No relevant cardiac, pharmacokinetic or safety interactions between roflumilast and inhaled formoterol in healthy subjects: an open-label, randomised, actively controlled study

doi: 10.1186/1472-6904-11-7

Figure Lengend Snippet: Geometric means (68% inter-percentile range) of the main pharmacokinetic variables for formoterol at steady state

Article Snippet: Determination of roflumilast and roflumilast N-oxide was performed at Altana Pharma AG, Konstanz, Germany (Nycomed GmbH).

Techniques:

Journal: BMC Clinical Pharmacology

Article Title: No relevant cardiac, pharmacokinetic or safety interactions between roflumilast and inhaled formoterol in healthy subjects: an open-label, randomised, actively controlled study

doi: 10.1186/1472-6904-11-7

Figure Lengend Snippet: Time course of the median cardiac output (CO) estimated by transthoracic impedance cardiography throughout the main profiling days . Regimen A: baseline Day 1 (NO treatment), Day 11 (R alone: roflumilast 500 μg once daily) and Day 18 (RF: roflumilast 500 μg once daily and formoterol 24 μg twice daily). Regimen B: baseline Day 1 (NO treatment), Day 8 (F alone: formoterol 24 μg twice daily) and Day 18 (FR: formoterol 24 μg twice daily and roflumilast 500 μg once daily).

Article Snippet: Determination of roflumilast and roflumilast N-oxide was performed at Altana Pharma AG, Konstanz, Germany (Nycomed GmbH).

Techniques:

Journal: BMC Clinical Pharmacology

Article Title: No relevant cardiac, pharmacokinetic or safety interactions between roflumilast and inhaled formoterol in healthy subjects: an open-label, randomised, actively controlled study

doi: 10.1186/1472-6904-11-7

Figure Lengend Snippet: Time course of the median total peripheral resistance (TPR) estimated by transthoracic impedance cardiography throughout the main profiling days . Regimen A: baseline Day 1 (NO treatment), Day 11 (R alone: roflumilast 500 μg once daily) and Day 18 (RF: roflumilast 500 μg once daily and formoterol 24 μg twice daily). Regimen B: baseline Day 1 (NO treatment), Day 8 (F alone: formoterol 24 μg twice daily) and Day 18 (FR: formoterol 24 μg twice daily and roflumilast 500 μg once daily).

Article Snippet: Determination of roflumilast and roflumilast N-oxide was performed at Altana Pharma AG, Konstanz, Germany (Nycomed GmbH).

Techniques:

Journal: BMC Clinical Pharmacology

Article Title: No relevant cardiac, pharmacokinetic or safety interactions between roflumilast and inhaled formoterol in healthy subjects: an open-label, randomised, actively controlled study

doi: 10.1186/1472-6904-11-7

Figure Lengend Snippet: Time course of the median heart rate throughout the main profiling days . Regimen A: baseline Day 1 (NO treatment), Day 11 (R alone: roflumilast 500 μg once daily) and Day 18 (RF: roflumilast 500 μg once daily and formoterol 24 μg twice daily). Regimen B: baseline Day 1 (NO treatment), Day 8 (F alone: formoterol 24 μg twice daily) and Day 18 (FR: formoterol 24 μg twice daily and roflumilast 500 μg once daily).

Article Snippet: Determination of roflumilast and roflumilast N-oxide was performed at Altana Pharma AG, Konstanz, Germany (Nycomed GmbH).

Techniques: