PMID- 30345935
OWN - NLM
STAT- MEDLINE
DCOM- 20200106
LR  - 20200106
IS  - 1874-0758 (Electronic)
IS  - 1872-3128 (Linking)
VI  - 13
IP  - 1
DP  - 2019
TI  - Comparison of Rat and Human Pulmonary Metabolism Using Precision-cut Lung Slices 
      (PCLS).
PG  - 53-63
LID - 10.2174/1872312812666181022114622 [doi]
AB  - 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.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Yilmaz, Yildiz
AU  - Yilmaz Y
AD  - Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, Basel, 
      Switzerland.
FAU - Williams, Gareth
AU  - Williams G
AD  - Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, Basel, 
      Switzerland.
FAU - Walles, Markus
AU  - Walles M
AD  - Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, Basel, 
      Switzerland.
FAU - Manevski, Nenad
AU  - Manevski N
AD  - Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, Basel, 
      Switzerland.
FAU - Krahenbuhl, Stephan
AU  - Krahenbuhl S
AD  - Clinical Pharmacology and Toxicology, University Hospital, Basel, Switzerland.
FAU - Camenisch, Gian
AU  - Camenisch G
AD  - Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, Basel, 
      Switzerland.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Drug Metab Lett
JT  - Drug metabolism letters
JID - 101313587
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
SB  - IM
MH  - Animals
MH  - Cytochrome P-450 Enzyme System/*metabolism
MH  - Female
MH  - Histocytological Preparation Techniques/*methods
MH  - Humans
MH  - Lung/*enzymology
MH  - Male
MH  - Models, Animal
MH  - Organ Culture Techniques
MH  - Pharmacology, Clinical/*methods
MH  - Rats
MH  - Species Specificity
OTO - NOTNLM
OT  - AFQ056
OT  - Precision-cut lung slices (PCLS)
OT  - dynamic organ culture system
OT  - human lung metabolism
OT  - pulmonary disposition of phase I and phase II drugs
OT  - rat and human pulmonary metabolism activity
OT  - rat lung metabolism.
EDAT- 2018/10/23 06:00
MHDA- 2020/01/07 06:00
CRDT- 2018/10/23 06:00
PHST- 2018/08/03 00:00 [received]
PHST- 2018/09/28 00:00 [revised]
PHST- 2018/10/08 00:00 [accepted]
PHST- 2018/10/23 06:00 [pubmed]
PHST- 2020/01/07 06:00 [medline]
PHST- 2018/10/23 06:00 [entrez]
AID - DML-EPUB-93865 [pii]
AID - 10.2174/1872312812666181022114622 [doi]
PST - ppublish
SO  - Drug Metab Lett. 2019;13(1):53-63. doi: 10.2174/1872312812666181022114622.