Assessing Human Lung Pharmacokinetics Using Exhaled Breath Particles

Background: It remains challenging to quantify lung pharmacokinetics (PK) of a drug administered and targeted to act in the lung. Exhaled breath particles (PEx), which are generated when collapsed distal airways reopen during inhalation, offer a noninvasive way to access undiluted epithelial lining fluid (ELF). Therefore, it was the aim of this study to investigate whether PK data can be derived from PEx. Methods: Six healthy volunteers received either an inhaled dose (400 µg) or an oral dose (8 mg) of salbutamol in a randomized, crossover design with 7-day washout between treatments. PEx were collected before and at nine time points after dosing (0-315 minutes [min]). Following each 15 min PEx sampling period, nasosorption and plasma samples were collected. Salbutamol was quantified by liquid chromatography-mass spectrometry. Results: After oral delivery and inhalation, salbutamol PK profiles could be obtained for plasma and nasal samples. In PEx samples, a PK profile could be obtained in 5 of 6 participants after inhalation, but the salbutamol concentration was often at or below detection limit after oral intake. After inhaled administration we found higher salbutamol concentrations in PEx as compared with nasal and plasma samples. Conclusion: This study provides proof of principle that PEx samples can be used to quantify drug levels in ELF.