| Interactions of cationic drugs and cardiac glycosides at the hepatic uptake level: studies in the rat in vivo, isolated perfused rat liver, isolated rat hepatocytes and oocytes expressing oatp2. | |
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MedLine Citation:
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PMID: 12214846 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This paper deals with a crucial mechanism for interaction of basic drugs and cardiac glycosides at the hepatic uptake level. Available literature data is provided and new material is presented to picture the differential transport inhibition of bulky (type2) cationic drugs by a number of cardiac glycosides in rat liver. It is shown that the so called organic anion transporting peptide 2 (oatp2) is the likely interaction site: differential inhibition patterns as observed in oocytes expressing oatp2, could be clearly identified also in isolated rat hepatocytes, isolated perfused rat liver and the rat in vivo. The anticipation of transport interactions at the hepatic clearance level should be based on data on the relative affinities of interacting substrates for the transport systems involved along with knowledge on the pharmacokinetics of these agents as well as the chosen dose regimen in the studied species. This review highlights the importance of multispecific tranporter systems such as OATP, accommodating a broad spectrum of organic compounds of various charge, implying potential transport interactions that can affect body distribution and organ clearance. |
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Authors:
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Dirk K F Meijer; Jessica E van Monffoort |
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Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: Archives of pharmacal research Volume: 25 ISSN: 0253-6269 ISO Abbreviation: Arch. Pharm. Res. Publication Date: 2002 Aug |
Date Detail:
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Created Date: 2002-09-06 Completed Date: 2003-03-18 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8000036 Medline TA: Arch Pharm Res Country: Korea (South) |
Other Details:
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Languages: eng Pagination: 397-415 Citation Subset: IM |
Affiliation:
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Department of Pharmacokinetics and Drug Delivery, Groningen University Institute of Drug Exploration, The Netherlands. D.K.F.Meijer@farm.rug.nl |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bile / metabolism Cardiac Glycosides / metabolism*, pharmacology* Cations Digitoxin / pharmacology Drug Interactions Hepatocytes / drug effects, enzymology, metabolism* Kinetics Liver / drug effects, enzymology, metabolism* Male Oocytes / drug effects, metabolism* Organic Anion Transport Polypeptide C / biosynthesis, genetics, metabolism* Ouabain / pharmacology Rats Rats, Wistar Sodium-Potassium-Exchanging ATPase / metabolism Strophanthins / pharmacology Tubocurarine / metabolism Xenopus laevis |
| Chemical | |
Reg. No./Substance:
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0/Cardiac Glycosides; 0/Cations; 0/Organic Anion Transport Polypeptide C; 0/Strophanthins; 33279-57-1/K-strophanthoside; 57-95-4/Tubocurarine; 630-60-4/Ouabain; 71-63-6/Digitoxin; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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