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Fatty acid binding protein is a major determinant of hepatic pharmacokinetics of palmitate and its metabolites.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Hung, Daniel Y. Burczynski, Frank J. Chang, Ping Lewis, Andrew G. J. Masci, Paul P. Siebert, Gerhard A. Anissimov, Yuri G. Roberts, Michael S. |
| Copyright Year | 2003 |
| Abstract | Disposition kinetics of [(3)H]palmitate and its low-molecular-weight metabolites in perfused rat livers were studied using the multiple-indicator dilution technique, a selective assay for [(3)H]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 [(3)H]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 [(3)H]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 [(3)H]palmitate also increased with increasing L-FABP levels. It is concluded that the variability in hepatic pharmacokinetics of unchanged [(3)H]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. |
| Starting Page | 2097 |
| Ending Page | 2106 |
| Page Count | 10 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://ajpgi.physiology.org/content/early/2002/11/20/ajpgi.00328.2002.full.pdf |
| Alternate Webpage(s) | http://ajpgi.physiology.org/content/ajpgi/284/3/G423.full.pdf |
| PubMed reference number | 12444013v1 |
| Volume Number | 284 |
| Issue Number | 3 |
| Journal | American journal of physiology. Gastrointestinal and liver physiology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Clofibrate FABP1 protein, human FABP3 protein, human FABP5 protein, human Fatty Acid-Binding Proteins Fatty Acids Glutathione S-Transferase Indicator Dilution Techniques Kinetics (discipline) Liver Metabolic Process, Cellular Metabolite Procedure disposition:Finding:Point in time:^Patient:Narrative Thioctic Acid Transferase palmitate |
| Content Type | Text |
| Resource Type | Article |
