Physiologically-based pharmacokinetic modeling after drug inhalation

Over the last decades, pharmacometric approaches became more widely applied to analyze the pharmacokinetics (PK) of drugs, ranging from empirical to mechanistic physiologically-based PK modeling. However, the number of published PBPK applications for orally inhaled drugs increased only recently, even though a mechanistic understanding would be essential when the local PK needs to be assessed to correctly infer on PK/PD relations. To illustrate how PBPK modeling can contribute to improve the understanding of the pulmonary fate of orally inhaled drugs, first the complex interplay of relevant pulmonary PK processes is explained and it is outlined how each of these can be incorporated into PBPK models. Besides theoretical considerations, examples are provided to review the current state of the art. Finally, this chapter provides an outlook on potential applications, opportunities but also limitations of PBPK modeling for orally inhaled drugs.