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Relationship Between Pharmacokinetic and Aerodynamic Particle Size Distribution Properties for Inhalers Containing Corticosteroids

Daley Yates PT.

Respiratory Drug Delivery 2014. Volume 1, 2014: 163-172.

Abstract:

For topically acting inhaled drugs, the ability of pharmacokinetic (PK) data to detect changes in lung deposition that may be relevant to efficacy in the airways has not been fully explored. To investigate this further aerodynamic particle size distribution (APSD) and PK data for two scenarios were evaluated. Firstly, where similar design metered dose inhalers (MDIs) were used to deliver different formulations and secondly, where essentially the same formulation was delivered from dry powder inhalers (DPIs) of different design. The MDI data comprised APSD and PK parameters for four dose strengths of three different beclomethasone dipropionate (BDP) products obtained from healthy subjects. The DPI data comprised APSD and PK parameters for fluticasone propionate (FP) obtained from healthy, asthmatic, or chronic obstructive pulmonary disease (COPD) subjects following administration of four different inhalers containing one or two strengths of FP blended with salmeterol (SAL) and lactose. For inhalers of similar design (MDIs), containing different formulations of the same drug, correlations were seen between PK endpoints, and APSD parameters driven mainly by the fine particle dose (FPD) and mass median aerodynamic diameter (MMAD). This finding was not replicated for inhalers of differing design (DPIs), containing similar drug lactose blends. In general, the PK data from BDP and FP inhalers appeared to reflect gross differences in the APSD within the same device while significant in vitro differences in individual and group stage data failed to impact the PK. The observation that small differences in APSD can result in similar PK parameters may arise, either because there were no meaningful differences in lung deposition or the PK may be insensitive to small differences in lung deposition. Products with similar PK parameters may not necessarily have the same pattern of regional lung deposition or efficacy outcomes.