TY - JOUR T1 - Lack of effect of mild and moderate hepatic impairment or UGT1A1 genotype on the pharmacokinetics of inhaled indacaterol JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p3988 AU - Paul Goldsmith AU - Sheryl Perry AU - Handan He AU - Ralph Woessner AU - Guenther Kaiser Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p3988.abstract N2 - Introduction and aim: Indacaterol (IND) is an inhaled long acting beta2 agonist for once-daily treatment of COPD. IND is highly protein bound and metabolized by CYP450 and UGT1A1. Therefore, hepatic impairment or low UGT1A1 activity (Gilbert Syndrome genotype) could potentially alter clearance of IND through changes in metabolic capacity and/or altered protein binding. Two open label studies were conducted to investigate these potential effects.Methods: The first study was a single centre, parallel group, single dose (IND 600μg) study in hepatically impaired and matched healthy subjects. The second was a parallel 14 day repeat dose study (IND 200μg once-daily) in healthy subjects with different UGT1A1 genotypes – the fully functional [(TA)6,(TA)6] (6/6) genotype and the low activity [(TA)7,(TA)7] (7/7) genotype (Gilbert syndrome). IND was determined in serum and urine (only first study) using a sensitive LC/MS/MS method. IND pharmacokinetics were compared to the respective control group, i.e. patients with mild and moderate impairment to matched healthy subjects, and UGT1A1 (7/7) to (6/6) genotype, with ratios of >1 indicating higher values in the test group.Results: For hepatically impaired subjects the ratios (impaired vs. controls) for AUC, Cmax and Ae (amount excreted in urine) ranged from 0.77–1.01; no change in ex-vivo protein binding was noted. In the comparison of UGT1A1 (7/7) to the (6/6) genotype, the ratios for AUC and Cmax on Day 1 and Day 14 ranged from 0.89–1.18.Conclusions: Taken together the pharmacokinetics of indacaterol are not significantly affected by mild and moderate hepatic impairment or UGT1A1 genotype. ER -