Investigating pulmonary and systemic pharmacokinetics of inhaled olodaterol in healthy volunteers using a population pharmacokinetic approach

British Journal of Clinical Pharmacology
Jens Markus BorghardtC Kloft

Abstract

Olodaterol, a novel β2-adrenergic receptor agonist, is a long-acting, once-daily inhaled bronchodilator approved for the treatment of chronic obstructive pulmonary disease. The aim of the present study was to describe the plasma and urine pharmacokinetics of olodaterol after intravenous administration and oral inhalation in healthy volunteers by population pharmacokinetic modelling and thereby to infer its pulmonary fate. Plasma and urine data after intravenous administration (0.5-25 μg) and oral inhalation (2.5-70 μg via the Respimat® inhaler) were available from a total of 148 healthy volunteers (single and multiple dosing). A stepwise model building approach was applied, using population pharmacokinetic modelling. Systemic disposition parameters were fixed to estimates obtained from intravenous data when modelling data after inhalation. A pharmacokinetic model, including three depot compartments with associated parallel first-order absorption processes (pulmonary model) on top of a four-compartment body model (systemic disposition model), was found to describe the data the best. The dose reaching the lung (pulmonary bioavailable fraction) was estimated to be 49.4% [95% confidence interval (CI) 46.1, 52.7%] of the dose releas...Continue Reading

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Citations

May 14, 2016·Expert Opinion on Investigational Drugs·Mario CazzolaJosuel Ora
May 6, 2016·British Journal of Clinical Pharmacology·Jens Markus BorghardtCharlotte Kloft
Apr 5, 2017·Biopharmaceutics & Drug Disposition·Konstantina SouleleVangelis Karalis
Mar 29, 2018·Drug Delivery·Erica BäckströmMarkus Fridén
Oct 13, 2018·Expert Opinion on Pharmacotherapy·Andrea S Melani
Jul 19, 2018·Canadian Respiratory Journal : Journal of the Canadian Thoracic Society·Jens Markus BorghardtAshish Sharma
Dec 16, 2020·PLoS Computational Biology·Niklas Hartung, Jens Markus Borghardt
Apr 26, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Astrid BaclePascal Le Corre
Sep 30, 2021·Journal of Pharmacokinetics and Pharmacodynamics·Anneke HimstedtSebastian Georg Wicha

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