Assessing the viability of long-acting β₂-agonists in paediatric asthma patients: a pharmacokinetic/pharmacodynamic perspective

ABSTRACT

Introduction: Long-acting β₂-agonists (LABAs) combined with inhaled corticosteroids (ICSs) are still commonly prescribed to asthmatic children. Unfortunately, pediatric LABA use is based primarily on data from adults, despite the fact that children are not simply small adults and the magnitude of changes in dose exposure and/or exposure response may not be solely reflected by differences in body weight.

Areas covered: The differences in pharmacokinetics (PK) and pharmacodynamics (PD) of LABAs are described and discussed with reference children and adults.

Expert opinion: Data on the PK behavior of LABAs is very limited and there is almost no data on once-daily LABAs available in the pediatric population. We do not believe that this is due to a fundamental lack of information because therapeutic response and adverse effects are more useful for the optimization of β₂-agonist treatment than measurement of plasma drug concentrations per se. Nevertheless, population PK-PD studies in children are needed according to the European rules in order to define rational, patient-tailored dosing schemes. Population PK-PD modeling and simulation using non-linear mixed effect modeling should be considered as the preferred tool to develop effective and safe dosing regimens for children because they present an opportunity to analyze sparse and unbalanced datasets, thereby minimizing the burden for each child.

KEYWORDS:

• Pharmacokinetics
• pharmacodynamics
• children
• long-acting β2-agonists

Article highlights

• LABAs combined with ICSs are still commonly prescribed drugs in asthmatic children. However, there is evidence that in children, combination therapy does not lead to a significant reduction, but rather it generates a trend towards an increased risk, of oral steroid-treated exacerbations and hospital admissions

• It is likely that the different effect of the addition of a LABA to an ICS in children compared to adults may lie in a different PK behaviour (dose exposure) that would lead to a different PD response (exposure response) in children.

• Paediatric LABA use is based primarily on data from adults, despite children are not small adults and the magnitude of changes in dose exposure and/or exposure response may not be solely reflected by differences in body weight.

• Regrettably, very limited data on the PK behaviour of LABAs and almost no data on that of once-daily LABAs are available in the paediatric population.

• PK-PD studies in children are needed in order to define well-adjusted, patient-tailored dosing schemes.

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Declaration of interest

M Cazzola has participated as a speaker, and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Lallemand, Mundipharma, Novartis, Pfizer, Verona Pharma, and Zambon, and is or has been a consultant to Chiesi Farmaceutici, Lallemand, Novartis, Ockham Biotech, Skyepharma, Verona Pharma, and Zambon. MG Matera has participated as a speaker, and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, and Novartis, and has been a consultant to Chiesi Farmaceutici. 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.

Additional information

Funding

This paper was not funded.