Linked Life Data

16488580

Source:http://linkedlifedata.com/resource/pubmed/id/16488580

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-3-13
pubmed:abstractText
Transporters play an important role in the processes of drug absorption, distribution and excretion. In this review, we have focused on the involvement of transporters in drug excretion in the liver and kidney. The rate of transporter-mediated uptake and efflux determines the rate of renal and hepatobiliary elimination. Transporters are thus important as a determinant of the clearance in the body. Even when drugs ultimately undergo metabolism, their elimination rate is sometimes determined by the uptake rate mediated by transporters. Transporters regulate the pharmacological and/or toxicological effect of drugs because they limit their distribution to tissues responsible for their effect and/or toxicity. For example, the liver-specific distribution of some statins via organic anion transporters helps them to produce their high pharmacological effect. On the other hand, as in the case of metformin taken up by organic cation transporter 1, drug distribution to the tissue(s) may enhance its toxicity. As transporter-mediated uptake is a determinant of the drug elimination rate, drug-drug interactions involving the process of transporter-mediated uptake can occur. In this review, we have introduced some examples and described their mechanisms. More recently, some methods to analyze such transporter-mediated transport have been reported. The estimation of the contributions of transporters to the net clearance of a drug makes it possible to predict the net clearance from data involving drug transport in transporter-expressing cells. Double transfected cells, where both uptake and efflux transporters are expressed on the same polarized cells, are also helpful for the analysis of the rate of transporter-mediated transcellular transport.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0928-0987
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
425-46
pubmed:meshHeading
pubmed-meshheading:16488580-Animals, pubmed-meshheading:16488580-Bile, pubmed-meshheading:16488580-Carbamates, pubmed-meshheading:16488580-Cell Line, pubmed-meshheading:16488580-Drug Interactions, pubmed-meshheading:16488580-Humans, pubmed-meshheading:16488580-Hydroxymethylglutaryl-CoA Reductase Inhibitors, pubmed-meshheading:16488580-Hypoglycemic Agents, pubmed-meshheading:16488580-Kidney, pubmed-meshheading:16488580-Liver, pubmed-meshheading:16488580-Membrane Transport Proteins, pubmed-meshheading:16488580-Metabolic Clearance Rate, pubmed-meshheading:16488580-Metformin, pubmed-meshheading:16488580-Organic Anion Transporters, pubmed-meshheading:16488580-Organic Cation Transport Proteins, pubmed-meshheading:16488580-P-Glycoprotein, pubmed-meshheading:16488580-Piperidines, pubmed-meshheading:16488580-Polymorphism, Genetic, pubmed-meshheading:16488580-Species Specificity, pubmed-meshheading:16488580-Tissue Distribution, pubmed-meshheading:16488580-Transfection
pubmed:year
2006
pubmed:articleTitle
Transporters as a determinant of drug clearance and tissue distribution.
pubmed:affiliation
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chou-ku, Chiba 260-8675, Japan.
pubmed:publicationType
Journal Article, Review