Exploratory Study of Inhaled Afatinib Dimaleate PK Profile

Participants will receive either a single dose of inhaled afatinib dimaleate or a 40 mgoral dose of afatinib dimaleate in a randomized sequence, with a 7‐day washout periodbetween treatments.The inhaled formulation of afatinib dimaleate is administered via a single‐use,maintenance‐free ultrasonic nebulizer (by SWITZERLAND TEAM) that generates aerosolparticles of a defined size, ensuring predictable bioavailability and targeted alveolardeposition. Each inhalation session consists of a predefined number of physiologicalbreaths, facilitating efficient drug uptake into the lungs at therapeutically relevantdoses.Key assessments include blood sampling for pharmacokinetic (PK), LC‐MS/MS, analysis,bronchoalveolar lavage (BAL) to evaluate pulmonary drug deposition, and spirometry toassess pulmonary safety.tests, CT.The investigators aim to obtain data on the role of pulmonary P‐glycoprotein (P‐gp)transporters in actively expelling afatinib dimaleate back into the alveolar space, aswell as its metabolism by cytochrome P450 enzymes (CYP3A4) during inhalation.Additionally, statistically significant data on both drug lung deposition (DLD) anddrug‐induced lung injury (DILI) will be analyzed.Pharmacokinetic parameters, including maximum plasma concentration (Cmax) and area underthe concentration‐time curve (AUC0‐∞), will be evaluated through plasma sampling. BALwill be performed in a subset of participants to assess direct pulmonary drug deposition.Safety and tolerability will be monitored through adverse event reporting, laboratorytesting, and spirometry.