Pharmacokinetic considerations surrounding triple therapy for uncontrolled asthma.

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.