Abstract
Introduction: FF is an ICS still active at 24h, being developed as once daily (OD) treatment in combination with vilanterol (VI) a long-acting beta2-agonist, for asthma and COPD. Early data suggested that FF systemic exposure might be higher in Japanese subjects than in Caucasians.
Objective: To evaluate and compare FF PK in Caucasian (Ca), Chinese (Ch) Japanese (J) and Korean (K) subjects following FF administration via a novel dry powder inhaler and i.v. infusion.
Methods: Open-label, randomised, two-way crossover study. Healthy male and female Ca, Ch, J and K subjects [N=20/group], randomised to receive OD inhaled FF (200mcg (7 days) then 800mcg (7 days)) and single i.v. 250mcg FF dose. PK data were obtained on D1 and/or D7.
Results: The inherent PK characteristics of i.v. FF were similar in Ca, Ch, J and K subjects, consistent with similar CYP3A4 activity in each population. Inhaled FF systemic exposure was higher at both doses (AUC ratio: 1.27 to 1.75) in Ch, J and K subjects, compared with Ca subjects, reflecting higher bioavailability (800mcg D7: 14.3% to 16.3% v 10.4%, respectively). Deconvolution analysis suggested that inhaled FF resided in the lungs of Ch, J and K subjects for longer than in Ca subjects, a likely reason for seeing greater bioavailability. All treatments were safe and well tolerated with no marked quantitative or qualitative differences in safety endpoints between the ethnic groups.
Conclusion: Following inhaled FF there was higher (< 2-fold) systemic exposure in Chinese, Japanese and Korean subjects compared with Caucasian subjects, although there were no safety or tolerability consequences.
Funded by GSK (HZA113477; NCT01000597)
- © 2011 ERS