Pharmacokinetics and safety of olodaterol administered with the respimat soft mist inhaler in subjects with impaired hepatic or renal function

Abstract

Purpose: In two trials, the influences of hepatic and renal impairment on the pharmacokinetics of olodaterol, a novel long-acting inhaled β2-agonist for treatment of COPD, were investigated. Subjects and methods: The first trial included eight subjects with mild hepatic function impairment (Child-Pugh A), eight subjects with moderate impairment (Child-Pugh B), and 16 matched healthy subjects with normal hepatic function. The second trial included eight subjects with severe renal impairment (creatinine clearance <30 mL⋅min-1) and 14 matched healthy subjects with normal renal function. Subjects received single doses of 20 or 30 μg olodaterol administered with the Respimat Soft Mist inhaler. Results: Olodaterol was well tolerated in all subjects. The geometric mean ratios and 90% confidence intervals of dose-normalized area under the plasma concentration-time curve from time zero to 4 hours (AUC0-4) for subjects with mild and moderate hepatic impairment compared to healthy subjects were 97% (75%-125%) and 105% (79%-140%), respectively. Corresponding values for dose-normalized maximum concentration (Cmax) were 112% (84%-151%) (mild impairment) and 99% (73%-135%) (moderate impairment). The geometric mean ratio (90% confidence interval) of AUC0-4 for subjects with severe renal impairment compared to healthy subjects was 135% (94%-195%), and for Cmax was 137% (84%-222%). There was no significant relationship between creatinine clearance and AUC0-4 or Cmax. Renal clearance of olodaterol was reduced to 20% of normal in severe renal impairment. Conclusion: Mild to moderate hepatic function impairment or severe renal function impairment did not result in a clinically relevant increase of olodaterol systemic exposure after a single inhaled dose.