Assessing the viability of long-acting β2-agonists in paediatric asthma patients: a pharmacokinetic/pharmacodynamic perspective.
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.
a Department of Experimental Medicine , Second University of Naples , Naples , Italy.
Maria Gabriella
MG
Matera
a Department of Experimental Medicine , Second University of Naples , Naples , Italy.
Barbara
B
Rinaldi
b Department of Systems Medicine , University of Rome Tor Vergata , Rome , Italy.
Luigino
L
Calzetta
b Department of Systems Medicine , University of Rome Tor Vergata , Rome , Italy.
Mario
M
Cazzola
D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000328:Adult; D000367:Age Factors; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008954:Models, Biological; D017711:Nonlinear Dynamics
D058666:Adrenergic beta-2 Receptor Agonists; D018927:Anti-Asthmatic Agents; D003692:Delayed-Action Preparations
Pharmacokinetics; children; long-acting β2-agonists; pharmacodynamics