Comparison of Rat and Human Pulmonary Metabolism Using Precision-cut Lung Slices (PCLS)
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Published:2019-04-30
Issue:1
Volume:13
Page:53-63
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ISSN:1872-3128
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Container-title:Drug Metabolism Letters
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language:en
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Short-container-title:DML
Author:
Yilmaz Yildiz1, Williams Gareth1, Walles Markus1, Manevski Nenad1, Krähenbühl Stephan2, Camenisch Gian1
Affiliation:
1. Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, Basel, Switzerland 2. Clinical Pharmacology and Toxicology, University Hospital, Basel, Switzerland
Abstract
<P>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. </P><P> 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. </P><P> 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.</P>
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology (medical),Biochemistry (medical),Clinical Biochemistry,Pharmaceutical Science
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