Submit Manuscript  

Article Details


Comparison of Rat and Human Pulmonary Metabolism Using Precision-cut Lung Slices (PCLS)

[ Vol. 13 , Issue. 1 ]

Author(s):

Yildiz Yilmaz*, Gareth Williams, Markus Walles, Nenad Manevski, Stephan Krähenbühl and Gian Camenisch   Pages 53 - 63 ( 11 )

Abstract:


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 here.

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.

Keywords:

Precision-cut lung slices (PCLS), rat lung metabolism, human lung metabolism, rat and human pulmonary metabolism activity, pulmonary disposition of phase I and phase II drugs, dynamic organ culture system, AFQ056.

Affiliation:

Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, Basel, Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, Basel, Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, Basel, Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, Basel, Clinical Pharmacology and Toxicology, University Hospital, Basel, Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, Basel

Graphical Abstract:



Read Full-Text article