Purpose
- Orally inhaled drug products (OIDPs) are used to treat pulmonary diseases. OIDP absorption occurs in three phases: deposition, dissolution, and permeation.
- Understanding the relationship between these three phases and the resulting local and systemic pharmacokinetic (PK) profiles is important for both pharmaceutical development and regulatory assessment of new and generic OIDPs.
- Predicting local and systemic human exposure for OIDPs is challenging, because deposition, dissolution, and permeability are difficult to estimate using in vitro or in vivo methods.
- Physiologically based pharmacokinetic (PBPK) modeling is an integrated solution to predicting local and systemic PK, which can support OIDP development. It includes regional deposition in the lung tissues, pulmonary physiological conditions, and active pharmaceutical ingredient (API) physicochemical characteristics that affect the API dissolution rate and permeability.
- To support the capability of an existing state-of-the-art lung PBPK model to accurately model permeability, this study aimed to evaluate the use of in vitro lung cell permeability assays to parameterize the model and predict in vivo PK. Tobramycin and fluticasone propionate were selected as validation case studies for this in vitro to in vivo extrapolation (IVIVE) method.
By James Mullin, Maxime Le Merdy, Steven Chopski, Ross Walenga, Elizabeth Bielski, Susan Boc, Andrew Clerman, Bryan Newman, Janny Pineiro-Llanes, Bassma Eltanameli, Rodrigo Cristofoletti
American Association of Pharmaceutical Scientists (AAPS) PharmSci 360, October 20-23, 2024, Salt Lake City, Utah