A Versatile Ex-Vivo Model Platform for Detection of Exhaled Drugs using Isolated Perfused Porcine Lungs

Background: Exhaled breath analysis (EBA) is a promising approach for drug monitoring. Although the range of drugs known to undergo pulmonary exhalation remains limited, innovative experimental models are needed to explore this field. This study aimed to develop an ex-vivo platform to systematically investigate drug exhalation, using propofol as validation compound due to its well-documented presence in exhaled breath. Methods: A porcine lung model was created using commercially slaughtered lungs. The lungs were then perfused and ventilated. Propofol exhalation was validated under various conditions (boluses, infusion rates, blood flow, and ventilation) using a propofol calibrated multi-capillary column-ion mobility spectrometer (MCC-IMS). Blood samples collected every 20 min were used to continuously monitor propofol plasma levels, and to perform blood gas analysis to assess pulmonary respiration and metabolism. Results: We established a functional ex-vivo platform using nine porcine lungs, with measurements extending up to 13 h. Physiological conditions were maintained, including 35 % hematocrit and 12 mg/dL hemoglobin, supported by glucose supplementation (921 mg/h). The observed mean lactate increase of 308 % reflected the expected metabolic activity under isolated organ perfusion, confirming the viability of the model without systemic interference. Conclusion: This ex-vivo model of perfused and ventilated porcine lungs offers a versatile platform for assessing the drug exhalation potential. It can identify candidate drugs for therapeutic monitoring and offers a humane alternative to animal studies. .