| Studies on the uptake of low molecular weight monomeric tris-galactosyl conjugates by the rat liver. | |
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MedLine Citation:
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PMID: 1472076 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have attempted to direct low molecular weight compounds to the liver via the internalizing asialoglycoprotein receptor on parenchymal cells by conjugation to a monomeric triantennary galactosyl cluster. Acetate and a hypolipidaemic ansamycin were derivatized and the biodistribution of the conjugates was determined 250 sec and 30 min after administration to Wistar rats. The ansamycin conjugate (CGH46) was rapidly cleared from the circulation by the liver; after 250 sec, 64% of the radiolabelled dose was found in the liver compared to 18% in the blood. However, the distribution of the conjugate did not differ significantly from that of unconjugated ansamycin (CGH45). Tris-galactosyl acetate showed no capacity to localize in the liver, with only 2% recovered from that organ 250 sec after administration compared to 38% in the blood and 13-18% in the kidneys, skin and muscle. Extraction efficiency of CGH46 by isolated perfused rat livers was almost 20% of the administered dose and this value was not significantly changed by co-administration of specific inhibitors of the uptake process. It is concluded that derivatization of low molecular weight molecules with monomeric triantennary galactosyl residues is unlikely to increase their affinity for the liver. |
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Authors:
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H G Eichler; K A Menear; K E Dunnet; J G Hastewell; P W Taylor |
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Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: Biochemical pharmacology Volume: 44 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 1992 Dec |
Date Detail:
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Created Date: 1993-01-28 Completed Date: 1993-01-28 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 2117-22 Citation Subset: IM |
Affiliation:
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Research and Preclinical Development, CIBA-Geigy Pharmaceuticals, Horsham, West Sussex, U.K. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetates
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pharmacokinetics Animals Anti-Bacterial Agents / pharmacokinetics* Asialoglycoprotein Receptor Binding, Competitive Galactosides / pharmacokinetics* Injections, Intravenous Lactams, Macrocyclic Ligands Liver / metabolism* Male Molecular Weight Perfusion Rats Rats, Wistar Receptors, Immunologic / metabolism Rifamycins / pharmacokinetics Tissue Distribution |
| Chemical | |
Reg. No./Substance:
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0/Acetates; 0/Anti-Bacterial Agents; 0/Asialoglycoprotein Receptor; 0/CGH45; 0/Galactosides; 0/Lactams, Macrocyclic; 0/Ligands; 0/Receptors, Immunologic; 0/Rifamycins; 146109-31-1/CGH46; 6998-60-3/rifamycin SV |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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