no relevant cardiac, pharmacokinetic or safety interactions between roflumilast and inhaled formoterol in healthy subjects an open-label, randomised, actively controlled study没有相关的心脏,药代动力学或安全roflumilast之间的相互作用和吸入formoterol在健康受试者一个非盲、随机,主动控制研究.pdfVIP

de Mey et al. BMC Clinical Pharmacology 2011, 11:7 /1472-6904/11/7 RESEARCH ARTICLE Open Access No relevant cardiac, pharmacokinetic or safety interactions between roflumilast and inhaled formoterol in healthy subjects: an open-label, randomised, actively controlled study 1 2 2* Christian de Mey , Nassr Nassr and Gezim Lahu Abstract Background: Roflumilast is an oral, selective phosphodiesterase 4 inhibitor with anti-inflammatory effects in chronic obstructive pulmonary disease (COPD). The addition of roflumilast to long-acting bronchodilators improves lung function in patients with moderate-to-severe COPD. The present study investigated drug-drug interaction effects between inhaled formoterol and oral roflumilast. Methods: This was a single-centre (investigational clinic), open, randomised, multiple-dose, parallel-group study. In Regimen A, healthy men were treated with roflumilast (500 μg tablet once daily; Day 2-18) and concomitant formoterol (24 μg twice daily; Day 12-18). In Regimen B, healthy men were treated with formoterol (24 μg twice daily; Day 2-18) and concomitant roflumilast (500 μg once daily; Day 9-18). Steady-state plasma pharmacokinetics of roflumilast, roflumilast N-oxide and/or formoterol (Cmax and AUC0-τ) as well as pharmacodynamics - blood pressure, transthoracic impedance cardiography (ZCG), 12-lead digital electrocardiography, peripheral blood eosinophils, and serum glucose and potassium concentrations - were evaluated through Day 1 (baseline), Day 8 (Regimen B: formoterol alone) or Day 11 (Regimen A: roflumilast alone), and Day 18 (Regimen A and B: roflumilast plus formoterol). Blood and urine samples were taken for safety assessment at screening, pharmacokinetic profiling days and Day 19. Adverse events were monitored through