Document Detail


Comparison of in vitro drug metabolism by lung, liver, and kidney of several common laboratory species.
MedLine Citation:
PMID:  240655     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Comparative studies of in vitro drug metabolism by hepatic and extrahepatic tissues have been complicated by the use of a single experimental tissue, few animal species, and variable experimental conditions. In an attempt to minimize these complications, liver, lung and kidney from rat, mouse, rabbit, hamster, and guinea pig were assayed for standard microsomal and soluble fraction enzymes involved in drug biotransformation. For all species, liver was the most active organ. Kidney and lung activities were usually 15%-40% of those found in liver, with kidney slightly more active than lung. No single species demonstrated total superiority in its drug-metabolizing ability, although hamster showed a large number of instances of greatest activity. The rat was a surprisingly poor representative of drug-metabolizing ability; it was superior to the other four species in less than 25% of the instances studied. All species appeared to N-demethylate aminopyrine equally except for high pulmonary and nearly absent renal activities in rabbit and high hepatic activity in hamster. Rat had the lowest level of cytochrome P-450 and low activity of NADPH-cytochrome c reductase. UDP-glucuronyltransferase activity toward the acceptors p-nitrophenol and o-aminophenol was higher in hamster and rabbit than other species. Guinea pig appeared to have the most active soluble fraction enzymes. Mouse lung and kidney had glutathione S-aryltransferase activities 10-fold greater than any other species and comparable to liver activity from rabbit and hamster.
Authors:
C L Litterst; E G Mimnaugh; R L Reagan; T E Gram
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  3     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:    1975 Jul-Aug
Date Detail:
Created Date:  1975-12-28     Completed Date:  1975-12-28     Revised Date:  2009-10-27    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  259-65     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acetyltransferases / metabolism
Aminopyrine N-Demethylase / metabolism
Aniline Hydroxylase / metabolism
Animals
Aryl Hydrocarbon Hydroxylases / metabolism
Cricetinae
Cytochrome P-450 Enzyme System / metabolism
Glucuronosyltransferase / metabolism
Guinea Pigs
Kidney / metabolism*,  ultrastructure
Liver / metabolism*,  ultrastructure
Lung / metabolism*,  ultrastructure
Male
Mice
Mice, Inbred Strains
Microscopy, Electron
Microsomes / enzymology,  metabolism
Microsomes, Liver / enzymology,  metabolism
NADPH-Ferrihemoprotein Reductase / metabolism
Pharmaceutical Preparations / metabolism*
Rabbits
Rats
Species Specificity
Chemical
Reg. No./Substance:
0/Pharmaceutical Preparations; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.14.-/Aniline Hydroxylase; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.5.3.-/Aminopyrine N-Demethylase; EC 1.6.2.4/NADPH-Ferrihemoprotein Reductase; EC 2.3.1.-/Acetyltransferases; EC 2.4.1.17/Glucuronosyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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