Pharmacokinetic considerations surrounding triple therapy for uncontrolled asthma

ABSTRACT

Introduction

Solid pharmacological rationale and clinical evidence support the use of a combination of an inhaled corticosteroid (ICS), a long-acting β₂-agonist, and a long-acting muscarinic antagonist in severe asthma, which clinically results in increased lung function, improved symptoms, and decreased exacerbation rates.

Areas covered

We examined the pharmacokinetic issues associated with triple therapy for uncontrolled asthma. We considered the pharmacokinetic characteristics of the three drug classes, the role of inhalers in influencing their pharmacokinetic behavior, and the impact of severe asthma on the pharmacokinetics of inhaled drugs.

Expert opinion

The pharmacokinetics of ICSs and bronchodilators are not affected to a great extent by severe asthma, according to a detailed review of the currently accessible literature. Compared to healthy people, patients with severe asthma show only minor variations in a few pharmacokinetic characteristics, which are unlikely to have therapeutic significance and do not require particular attention. However, the difficulty of obtaining pharmacokinetic profiles of the three drugs included in a triple therapy suggests that the clinical response should be followed over time, which can be considered a good surrogate indicator of whether the drugs have reached sufficient concentrations in the lung to exert a valid pharmacological action.

KEYWORDS:

• Asthma
• ICS
• LABA
• LAMA
• triple therapy
• pharmacokinetics

Article highlights

• The use of inhaled triple therapy with an ICS, a LABA, and a LAMA in uncontrolled asthma is now codified by national and international guidelines and strategy documents.

• The therapeutic effect of aerosolized treatments depends on their pharmacokinetic behavior, particularly pulmonary bioavailability.

• Differences in the pharmacokinetic characteristics of each of the three drugs in any combination can critically influence its profile.

• The delivery method utilized for inhalation and the presence of lung disease per se can affect the pharmacokinetics of inhaled drugs.

• The pharmacokinetics of ICSs and bronchodilators are not affected to a great extent by severe asthma, according to a detailed review of the currently accessible literature.

• The clinical response over time is a reliable surrogate indicator that the drugs have reached sufficient concentrations in the lung to exert an effective pharmacological action.

Declaration of interest

M G Matera has participated as a speaker and/or advisor in scientific meetings and courses under the sponsorship of ABC Farmaceutici, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, and Novartis and has been a consultant to ABC Farmaceutici, GlaxoSmithKline, and Chiesi Farmaceutici. L Calzetta has participated as an advisor in scientific meetings under the sponsorship of Boehringer Ingelheim and Novartis; received non-financial support from AstraZeneca; a research grant partially funded by Chiesi Farmaceutici, Boehringer Ingelheim, Novartis and Almirall; and is or has been a consultant to ABC Farmaceutici, Edmond Pharma, Ockham Biotech, VeronaPharma and Zambon. M Cazzola has participated as a speaker and/or advisor in scientific meetings and courses under the sponsorship of Abdi Ibrahim, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Cipla, Edmond Pharma, GlaxoSmithKline, Glenmark, Lallemand, Malesci/Guidotti, Mundipharma, Novartis, Sanofi, Verona Pharma and Zambon; and has been a consultant to ABC Farmaceutici, Chiesi Farmaceutici, Edmond Pharma, Lallemand, Novartis, Ockham Biotech, Verona Pharma and Zambon. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.