Inferring pulmonary exposure based on clinical PK data: accuracy and precision of model-based deconvolution methods.

ABSTRACT: Determining and understanding the target-site exposure in clinical studies remains challenging. This is especially true for oral drug inhalation for local treatment, where the target-site is identical to the site of drug absorption, i.e., the lungs. Modeling and simulation based on clinical pharmacokinetic (PK) data may be a valid approach to infer the pulmonary fate of orally inhaled drugs, even without local measurements. In this work, a simulation-estimation study was systematically applied to investigate five published model structures for pulmonary drug absorption. First, these models were compared for structural identifiability and how choosing an inadequate model impacts the inference on pulmonary exposure. Second, in the context of the population approach both sequential and simult

SUBMITTER: Himstedt A 

PROVIDER: S-EPMC8940815 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature