| Effect of colchicine-specific Fab fragments on the hepatic clearance of colchicine. | |
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MedLine Citation:
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PMID: 7905405 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The influence of colchicine-specific Fab fragments on hepatic metabolism and biliary excretion of colchicine was studied in the isolated perfused rat liver. Isolated rat livers were perfused for 180 min with either [3H]colchicine (initial concentration: 50 ng/ml) or Fab-[3H] colchicine in a stoichiometrical proportion at a constant flow of 100 ml/min in a recirculating system. Based on perfusate concentrations, the hepatic extraction ratio of colchicine was more than 15-fold decreased when colchicine was bound to Fab fragments (E = 0.011 +/- 0.001) than when it was infused alone (E = 0.16 +/- 0.01) (p < 0.01). The extensive binding of colchicine to Fab over the experimental period as demonstrated by equilibrium dialysis (97 +/- 2%) prevented hepatic uptake. At the end of the colchicine perfusion experiment, 74.2 +/- 4.9% of the radioactivity infused was excreted by the biliary route. In contrast, biliary excretion of radioactivity was 10-fold lower when [3H]colchicine was perfused complexed with Fab fragments (p < 0.01). However, the metabolic profile of colchicine was not affected by Fab fragments. The apparent half-life of colchicine metabolites calculated from biliary data was similar to that of colchicine, indicating that the biliary excretion of these metabolites was formation rate-limited. Inhibition of colchicine uptake by specific Fab fragment was confirmed in vitro with isolated hepatocytes. |
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Authors:
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A Sabouraud; M Redureau; P Gires; M Martinet; J M Scherrmann |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Drug metabolism and disposition: the biological fate of chemicals Volume: 21 ISSN: 0090-9556 ISO Abbreviation: Drug Metab. Dispos. Publication Date: 1993 Nov-Dec |
Date Detail:
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Created Date: 1994-03-04 Completed Date: 1994-03-04 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9421550 Medline TA: Drug Metab Dispos Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 997-1002 Citation Subset: IM |
Affiliation:
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INSERM U26, Paris, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibody Specificity Bile / chemistry, drug effects, metabolism Biliary Tract / drug effects, metabolism Cells, Cultured Colchicine / immunology, metabolism, pharmacokinetics* Half-Life Immunoglobulin Fab Fragments / pharmacology* Liver / drug effects*, metabolism* Male Models, Biological Rats Rats, Sprague-Dawley Tritium |
| Chemical | |
Reg. No./Substance:
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0/Immunoglobulin Fab Fragments; 10028-17-8/Tritium; 64-86-8/Colchicine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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