Pharmacokinetics of budesonide and formoterol administered via a series of single‐drug and combination inhalers: four open‐label, randomized, crossover studies in healthy adults

Objective : To investigate the pharmacokinetics of budesonide and formoterol administered concomitantly in healthy adults. Methods : Three single‐dose, open‐label crossover studies ( n =28 each) were conducted (Study I: budesonide pMDI, formoterol DPI, budesonide pMDI+formoterol DPI; Study II: budesonide/formoterol pMDI, budesonide pMDI+formoterol DPI; Study III: budesonide/formoterol pMDI [three budesonide formulation strengths; constant formoterol]). Study IV ( n =28) assessed steady state pharmacokinetics (budesonide/formoterol pMDI [two/four inhalations twice daily, 5‐day treatment; four inhalations, single‐dose]). Results : Study I: no pharmacokinetic interactions were observed between budesonide and formoterol. Study II: AUC ratios were 97.9% (budesonide) and 82.2% (formoterol) (budesonide/formoterol pMDI versus budesonide pMDI+formoterol DPI). Study III: formoterol AUC was comparable across budesonide/formoterol pMDI formulation strengths; budesonide AUC increased with formulation strength in proportion to fine particle dose. Study IV: dose proportionality was demonstrated for budesonide ( AUC ratio, 104.3%) and suggested for formoterol ( AUC ratio, 117.6%) with budesonide/formoterol pMDI (steady state); budesonide and formoterol AUC was higher with repeated versus single‐dose budesonide/formoterol pMDI (four inhalations). Conclusions : No pharmacokinetic interactions were observed between budesonide and formoterol. Budesonide dose variation in budesonide/formoterol pMDI did not affect formoterol exposure. Steady state budesonide/formoterol pMDI dose‐doubling yielded proportional increases in budesonide and formoterol exposure. Copyright © 2008 John Wiley & Sons, Ltd.