Assessing Human Lung Pharmacokinetics Using Exhaled Breath Particles.

Area of Science:

• Pharmacology
• Pulmonary Medicine
• Analytical Chemistry

Background:

• Quantifying lung drug pharmacokinetics (PK) for lung-targeted therapies remains a significant challenge.
• Exhaled breath particles (PEx) offer a noninvasive method to access undiluted epithelial lining fluid (ELF).
• This study explores the potential of PEx for deriving lung PK data.

Purpose of the Study:

• To investigate the feasibility of deriving pharmacokinetic (PK) data from exhaled breath particles (PEx).
• To compare drug concentrations in PEx with plasma and nasal samples following different administration routes.

Main Methods:

• A randomized, crossover study involving healthy volunteers receiving inhaled or oral salbutamol.
• Collection of PEx, nasal, and plasma samples at multiple time points post-dosing.
• Quantification of salbutamol using liquid chromatography-mass spectrometry.

Main Results:

• Salbutamol PK profiles were successfully obtained from plasma and nasal samples for both administration routes.
• PK profiles from PEx were achievable in most participants after inhalation, but often below detection limits after oral intake.
• Inhaled salbutamol showed higher concentrations in PEx compared to nasal and plasma samples.

Conclusions:

• Exhaled breath particles (PEx) provide a viable noninvasive method for quantifying drug levels in the lung's epithelial lining fluid (ELF).
• This proof-of-principle study supports the use of PEx for lung drug pharmacokinetic assessments.