dc.contributor.author | Y. Hung, Daniel | |
dc.contributor.author | J. Burczynski, Frank | |
dc.contributor.author | Chang, Ping | |
dc.contributor.author | Lewis, Andrew | |
dc.contributor.author | P. Masci, Paul | |
dc.contributor.author | A. Siebert, Gerhard | |
dc.contributor.author | Anissimov, Yuri G. | |
dc.contributor.author | S. Roberts, Michael | |
dc.date.accessioned | 2017-05-03T15:13:51Z | |
dc.date.available | 2017-05-03T15:13:51Z | |
dc.date.issued | 2003 | |
dc.identifier.issn | 01931857 | |
dc.identifier.uri | http://hdl.handle.net/10072/20305 | |
dc.description.abstract | Disposition 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.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | American Physiological Society | |
dc.publisher.place | United States | |
dc.publisher.uri | http://ajpgi.physiology.org/content/284/3/G423 | |
dc.relation.ispartofpagefrom | 423 | |
dc.relation.ispartofpageto | 433 | |
dc.relation.ispartofjournal | American Journal of Physiology: Gastrointestinal and Liver Physiology | |
dc.relation.ispartofvolume | 284 | |
dc.subject.fieldofresearch | Physiology | |
dc.subject.fieldofresearch | Medical Physiology | |
dc.subject.fieldofresearchcode | 0606 | |
dc.subject.fieldofresearchcode | 1116 | |
dc.title | Fatty acid binding protein is a major determinant of hepatic pharmacokinetics of palmitate and its metabolites. | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
gro.rights.copyright | Self-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.issued | 2015-02-05T03:42:58Z | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Anissimov, Yuri G. | |