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dc.contributor.authorY. Hung, Daniel
dc.contributor.authorJ. Burczynski, Frank
dc.contributor.authorChang, Ping
dc.contributor.authorLewis, Andrew
dc.contributor.authorP. Masci, Paul
dc.contributor.authorA. Siebert, Gerhard
dc.contributor.authorAnissimov, Yuri G.
dc.contributor.authorS. Roberts, Michael
dc.date.accessioned2017-05-03T15:13:51Z
dc.date.available2017-05-03T15:13:51Z
dc.date.issued2003
dc.identifier.issn01931857
dc.identifier.urihttp://hdl.handle.net/10072/20305
dc.description.abstractDisposition kinetics of [3H]palmitate and its low-molecular-weight metabolites in perfused rat livers were studied using the multiple-indicator dilution technique, a selective assay for [3H]palmitate and its low-molecular-weight metabolites, and several physiologically based pharmacokinetic models. The level of liver fatty acid binding protein (L-FABP), other intrahepatic binding proteins (microsomal protein, albumin, and glutathione S-transferase) and the outflow profiles of [3H]palmitate and metabolites were measured in four experimental groups of rats: 1) males; 2) clofibrate-treated males; 3) females; and 4) pregnant females. A slow-diffusion/bound model was found to better describe the hepatic disposition of unchanged [3H]palmitate than other pharmacokinetic models. The L-FABP levels followed the order: pregnant female > clofibrate-treated male > female > male. Levels of other intrahepatic proteins did not differ significantly. The hepatic extraction ratio and mean transit time for unchanged palmitate, as well as the production of low-molecular-weight metabolites of palmitate and their retention in the liver, increased with increasing L-FABP levels. Palmitate metabolic clearance, permeability-surface area product, retention of palmitate by the liver, and cytoplasmic diffusion constant for unchanged [3H]palmitate also increased with increasing L-FABP levels. It is concluded that the variability in hepatic pharmacokinetics of unchanged [3H]palmitate and its low-molecular-weight metabolites in perfused rat livers is related to levels of L-FABP and not those of other intrahepatic proteins.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Physiological Society
dc.publisher.placeUnited States
dc.publisher.urihttp://ajpgi.physiology.org/content/284/3/G423
dc.relation.ispartofpagefrom423
dc.relation.ispartofpageto433
dc.relation.ispartofjournalAmerican Journal of Physiology: Gastrointestinal and Liver Physiology
dc.relation.ispartofvolume284
dc.subject.fieldofresearchPhysiology
dc.subject.fieldofresearchMedical Physiology
dc.subject.fieldofresearchcode0606
dc.subject.fieldofresearchcode1116
dc.titleFatty acid binding protein is a major determinant of hepatic pharmacokinetics of palmitate and its metabolites.
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyrightSelf-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.
gro.date.issued2015-02-05T03:42:58Z
gro.hasfulltextNo Full Text
gro.griffith.authorAnissimov, Yuri G.


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