Pharmacokinetic considerations concerning the use of bronchodilators in the treatment of chronic obstructive pulmonary disease

ABSTRACT

Introduction: Bronchodilators are central to the symptomatic treatment of chronic obstructive pulmonary disease (COPD). Their pharmacodynamic aspects have been extensively described, but the pharmacokinetic profile of these drugs is much less well known. There are very few studies that describe the levels of drugs in the lung compartment following inhalation, and still very little is known about the relationships between drug levels in the lung and biological activity of bronchodilators.

Areas covered: We review the existing evidence on the pharmacokinetics of bronchodilators, especially when administered to patients with COPD.

Expert opinion: COPD does not substantially influence the pharmacokinetics of bronchodilators, although a modest signal, perhaps, exists for theophylline. We must highlight that plasma pharmacokinetics is suitable for establishing a systemic safety profile of inhaled bronchodilators but not their pulmonary efficacy profile because measurement of systemic blood values is neither at the site of action nor representative of transport to the site of action (the airways). However, there are large amounts of information from research in this field and recent advances with microdialysis and matrix-assisted laser desorption-ionization time-of-flight mass spectrometry to measure drugs in lung tissues that hopefully will lead to a better understanding of the pharmacokinetic/pharmacodynamic relationships for inhaled medicines.

KEYWORDS:

• Bronchodilators
• COPD
• pharmacokinetics
• β₂-agonists
• muscarinic receptor antagonists
• xanthines

Article highlights

• Plasma pharmacokinetics of bronchodilators is suitable for establishing a systemic safety profile while not for establishing a pulmonary efficacy profile. Measurement of systemic blood values is neither at the site of action nor representative of transport to the site of action (the airways)

• There are very few studies that describe the levels of bronchodilators in the lung compartment following inhalation, and so far less is known about the relationships between drug levels in the lung and biological activity.

• Recent advances with microdialysis and MALDI-TOF MS to measure drugs in lung tissues hopefully will lead to better pharmacokinetics/pharmacodynamics relationships to be determined for inhaled medicines.

• A careful analysis of the available literature suggests that COPD generally does not significantly influence the pharmacokinetics of bronchodilators. The modest differences in some pharmacokinetic parameters recorded in patients with COPD compared to healthy subjects are of doubtful clinical relevance.

• There are many indirect influences on the pharmacokinetics of bronchodilators in patients with COPD that must be always considered.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This article was not funded.