PT  - JOURNAL ARTICLE
AU  - Ann Allen
AU  - Kelly Hardes
AU  - Rodger Kempsford
AU  - Lee Tombs
TI  - The pharmacokinetics (PK) and pharmacodynamics (PD) of the fluticasone furoate (FF) and vilanterol (VI) combination in subjects with severe renal impairment
DP  - 2012 Sep 01
TA  - European Respiratory Journal
PG  - P2151
VI  - 40
IP  - Suppl 56
4099  - http://erj.ersjournals.com/content/40/Suppl_56/P2151.short
4100  - http://erj.ersjournals.com/content/40/Suppl_56/P2151.full
SO  - Eur Respir J2012 Sep 01; 40
AB  - Introduction: A combination of the novel corticosteroid FF and long-acting beta2 agonist VI (FF/VI) is being developed as a once-daily inhaled treatment for asthma and COPD.Objectives: To investigate the effect of severe renal impairment on FF and VI PK and PD.Methods: Open-label, parallel group study of repeat dose once-daily FF/VI 200/25mcg (7 days) in 9 subjects with severe renal impairment (CrCl<30mL/min) and 9 matched control healthy subjects (by gender, ethnicity, age (±5 years) and BMI (±15%)). FF and VI PK parameters were assessed on Day 7. PK parameter point estimates (90% confidence interval [CI]) were constructed for the ratio of geometric means (renally impaired:healthy subjects). Non-inferiority was to be concluded if the upper 90% CI for the ratio was <2 for the Day 7 comparison. Systemic PD effects of FF (0–24h serum cortisol) and VI (0–4h heart rate and serum potassium) were assessed on Day 7.Results: For FF AUC(0–24) and Cmax the geometric mean ratio [90% CI] for renal:healthy was 0.91 [0.60, 1.38] and 0.96 [0.57, 1.61], respectively. For VI AUC(0–24) and Cmax the geometric mean ratio [90% CI] for renal: healthy was 1.56 [1.27, 1.92] and 0.70 [0.49, 1.00], respectively. Administration of FF/VI 200/25mcg to subjects with severe renal impairment did not result in significantly greater effects on serum cortisol, heart rate or serum potassium compared with healthy subjects.Conclusions: There was no evidence of clinically relevant increases in FF or VI systemic exposure or systemic pharmacodynamic effects in subjects with severe renal impairment compared with healthy subjects.Funded by GSK (HZA113970; NCT01266980).