PT - JOURNAL ARTICLE AU - Ann Allen AU - Joseph Bianco AU - Joanne Bal AU - Lee Tombs AU - Rodger Kempsford TI - The absolute bioavailability of fluticasone furoate (FF) and vilanterol (VI) trifenatate following inhaled administration in combination in healthy subjects DP - 2011 Sep 01 TA - European Respiratory Journal PG - p3976 VI - 38 IP - Suppl 55 4099 - http://erj.ersjournals.com/content/38/Suppl_55/p3976.short 4100 - http://erj.ersjournals.com/content/38/Suppl_55/p3976.full SO - Eur Respir J2011 Sep 01; 38 AB - Introduction: A combination of the novel corticosteroid FF and long acting beta2-agonist VI (FF/VI) is currently under development as a once-daily inhaled treatment for asthma and COPD.Objective: To determine the absolute bioavailability of FF and VI when administered in combination as FF/VI from a novel dry powder inhaler in healthy subjects.Methods: In this open-label, non-randomised, three-way crossover, single-dose study, male and female subjects [N=16] received (in order) a single inhaled dose of FF/VI 800/100mcg (4 inhalations of 200/25mcg), a single 250mcg intravenous (i.v.) dose of FF and a single 55mcg i.v. dose of VI. FF and VI pharmacokinetic data were obtained up to 48h post-dose.Results: The average absolute bioavailability of FF when inhaled as FF/VI relative to i.v. FF was 15% (90% CI: 13, 18). The average absolute bioavailability of VI when inhaled as FF/VI relative to i.v. VI was 27% (90% CI: 22, 35). Both FF and VI were rapidly cleared and widely distributed following i.v. dosing. FF showed longer retention in the lung than VI following inhaled administration with the time for 90% of the total to be absorbed from the lung on average, 35.2h and 3.8h, respectively. All treatments were safe and well tolerated even though this study evaluated multiples of the likely inhaled therapeutic dose (200/25mcg).Conclusion: In healthy adult subjects the absolute bioavailability of FF was 15% and for VI was 27% following a single inhaled dose of FF/VI delivered via a novel dry powder inhaler.Funded by GSK (HZA102934, NCT01299558)