Document Detail


Metabolism of the new ribonucleotide reductase inhibitor amidox in the isolated perfused rat liver.
MedLine Citation:
PMID:  11131656     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Amidox (AX) is a novel anticancer drug currently undergoing pre-clinical studies. Though AX shows activity against various tumor cells, its biotransformation is still unknown. MATERIAL AND METHODS: Livers of male Wistar and mutant TR- rats were perfused with AX in a single pass system and bile and effluent perfusate analyzed by HPLC for AX and its metabolites. RESULTS: In bile, seven biotransformation products but not AX could be quantified though their total excretion into bile was low. However, the cumulative efflux of AX metabolites into the effluent perfusate was high with about 55% of AX applied to the liver during perfusion. Biliary excretion of AX metabolites in TR- rats was substantially reduced compared to Wistar rats, indicating that metabolites are substrates of the canalicular multispecific organic anion transporter cmoat. CONCLUSION: Metabolism of AX in rat liver is high and has to be considered during cancer therapy of patients.
Authors:
A Salamon; E Vielnascher; B Hagenauer; T Szekeres; M Szekeres-Fritzer; T Thalhammer; W Jäger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  20     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2000 Sep- Oct
Date Detail:
Created Date:  2000-12-21     Completed Date:  2001-01-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  3521-6     Citation Subset:  IM    
Affiliation:
Institute of Pharmaceutical Chemistry, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anion Transport Proteins
Antineoplastic Agents / metabolism,  pharmacokinetics*
Bile / metabolism
Biotransformation
Carrier Proteins / genetics,  metabolism
Chromatography, High Pressure Liquid
Drug Resistance, Neoplasm
Enzyme Inhibitors / metabolism,  pharmacokinetics
Liver / metabolism*
Male
Oximes / metabolism,  pharmacokinetics*
Perfusion
Rats
Rats, Mutant Strains
Rats, Wistar
Ribonucleotide Reductases / antagonists & inhibitors
Chemical
Reg. No./Substance:
0/Anion Transport Proteins; 0/Antineoplastic Agents; 0/Carrier Proteins; 0/Enzyme Inhibitors; 0/Oximes; 95933-72-5/Amidox; EC 1.17.4.-/Ribonucleotide Reductases

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