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The pharmacokinetics of multiple inhaled NVA237 doses in patients with chronic obstructive pulmonary disease (COPD)

Sechaud, Romain and Renard, Didier and Zhang Auberson, Lixin and De la Motte, Stephan and Drollmann, Anton Franz and Kaiser, Guenther (2012) The pharmacokinetics of multiple inhaled NVA237 doses in patients with chronic obstructive pulmonary disease (COPD). International Journal of Clinical Pharmacology and Therapeutics, 50 (2). pp. 118-128. ISSN 0946-1965

Abstract

Objective: NVA237 (glycopyrronium bromide) is a once-daily long-acting muscarinic antagonist (LAMA) in development for the treatment of chronic obstructive pulmonary disease (COPD). This study investigated the pharmacokinetics (PK) of NVA237 following single and repeated once-daily inhalation in mild to moderate COPD patients.
Methods: In this double-blind, parallel-group study, COPD patients were randomised to a 14-day treatment with NVA237 (25, 50, 100 or 200 μg) or placebo. Plasma concentration-time profiles and urinary excretion of NVA237 were determined on Days 1 and 14.
Results: The median time to reach maximal plasma concentration (tmax) was 5 or 6.5 min post-inhalation. At steady state (Day 14), total and maximum systemic exposure (AUC0-24, Cmax) to NVA237 and urinary excretion of unchanged drug (Ae0-24) was approximately dose proportional over the 50 to 200 µg dose range. The average exposure was 1.4- to 1.7-fold higher on Day 14 compared with Day 1. The mean terminal elimination half-life (t½) of NVA237 ranged between 13 and 22 h. Steady-state plasma concentrations were reached within one week of treatment. Renal clearance (CLR) was similar across doses both after single and repeated dosing, ranging between 17.4 and 20.6 L/h. Urinary excretion of NVA237 enantiomers ([3S,2R]- and [3R,2S]-stereoisomers) was similar with respect to the amount excreted within 24 h and the excretion rate.
Conclusions: The pharmacokinetics of NVA237 were consistent between doses with limited systemic accumulation at steady state after repeated once-daily inhalation

Item Type: Article
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Keywords: NVA237; COPD; LAMA; systemic exposure; pharmacokinetics; spirometry
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Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15
URI: https://oak.novartis.com/id/eprint/5366

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