Pharmacokinetics of Glycopyrronium Following Repeated Once-Daily Inhalation in Healthy Chinese Subjects.

Background And Objectives: Glycopyrronium is a once-daily long-acting muscarinic antagonist for the maintenance treatment of patients with chronic obstructive pulmonary disease. This study assessed the pharmacokinetics of inhaled glycopyrronium 50 µg once-daily for 14 days in healthy Chinese subjects.

Methods: In this open-label study, 12 Chinese healthy subjects (six males and six females; mean age 23.1 years [range 18-26 years]) were enrolled and completed the study. Glycopyrronium in plasma was determined using validated liquid chromatography-mass spectrometry method with a lower limit of quantification of 1.5 pg/mL. Plasma pharmacokinetic parameters were determined on Day 1 after first dose and on Day 14 (steady state) after last dose using non-compartmental analysis. Trough pharmacokinetic samples (Days 5, 7, 10 and 12) were collected. Safety was also assessed.

Results: Glycopyrronium was rapidly absorbed into the systemic circulation after inhalation and its plasma concentrations decreased rapidly thereafter. Median time to reach maximum concentration (T ) was reached within 5 min after inhalation on both Days 1 and 14. Accumulation in the systemic exposure to glycopyrronium was observed from the time of first dose administration on Day 1 up to Day 14 and the observed accumulation ratio (R ) values of area under the plasma drug concentration-time curve [AUC] from time 0 to 24 h post-dose (AUC) and maximum plasma drug concentration (C ) (Day 14/Day 1) were 2.77 and 1.59, respectively. The elimination half-life (T ) was not reported. Mean effective half-life (T ) was 37.7 h. Pharmacokinetic steady state was reached after 5 days of daily dosing. One subject experienced dry mouth; otherwise glycopyrronium was well tolerated.

Conclusions: Comparison of systemic exposure to glycopyrronium in Chinese versus the non-Chinese population did not indicate clinically relevant ethnic differences. Multiple inhaled doses of glycopyrronium were safe and well tolerated.