Pharmacokinetics of tiotropium administered by Respimat in adolescent asthma patients

Introduction: Tiotropium Respimat ® has been shown to be well tolerated and efficacious as add-on to maintenance ICS±LABA treatment in adolescents (12–17 years) with moderate to severe asthma. Pharmacokinetics (PK) have been studied in adult patients but the PK of tiotropium in adolescents needs elucidation. Aims: We studied PK characteristics of tiotropium, following single and multiple doses, in adolescent patients with moderate persistent asthma. Methods: PK parameters of tiotropium were evaluated in blood and urine samples from a subset of adolescent patients (n=52) in a Phase II, randomised, double-blind, placebo-controlled, crossover trial of tiotropium Respimat ® (1.25μg, 2.5μg, and 5μg, 2 puffs added-on to ICS). PK were determined after the first dose (first treatment only) and after 4 weeks of dosing for all treatments in the study. Results: Tiotropium was rapidly absorbed with median t max ss of 4–6min post-dosing. Plasma concentrations changed rapidly during the initial 30min; changes were minimal from 30min–24h. An average of 3.28–4.24% of the inhaled dose following single dose and 12.6–14.3% following multiple dosing was excreted unchanged in urine over 24h. PK values were approximately dose proportional. Based on the PK of the 5μg dose, steady-state was achieved by Day 26. Dosing to steady-state resulted in 1.26-fold higher C max (3.95pg/mL), 1.25-fold higher AUC 0-0.167 (0.518pg/mL) and 3.1-fold higher urinary excretion of tiotropium compared with the single dose of 5μg. Conclusion: These data establish the PK of tiotropium Respimat ® following administration of a single dose and at steady-state in adolescent patients with moderate asthma, and are in line with previously reported adult data.