Background: Although the liver is the primary organ of drug metabolism, the lungs also
contain drug-metabolizing enzymes and may, therefore, contribute to the elimination of drugs. In this
investigation, the Precision-cut Lung Slice (PCLS) technique was standardized with the aims of characterizing
and comparing rat and human pulmonary drug metabolizing activity.
Method: Due to the limited availability of human lung tissue, standardization of the PCLS method was
performed with rat lung tissue. Pulmonary enzymatic activity was found to vary significantly with rat
age and rat strain. The Dynamic Organ Culture (DOC) system was superior to well-plates for tissue incubations,
while oxygen supply appeared to have a limited impact within the 4h incubation period used
Results: The metabolism of a range of phase I and phase II probe substrates was assessed in rat and
human lung preparations. Cytochrome P450 (CYP) activity was relatively low in both species, whereas
phase II activity appeared to be more significant.
Conclusion: PCLS is a promising tool for the investigation of pulmonary drug metabolism. The data
indicates that pulmonary CYP activity is relatively low and that there are significant differences in enzyme
activity between rat and human lung.