| Autor: |
Hung, Daniel Y., Burczynski, Frank J., Ping Chang, Lewis, Andrew, Masci, Paul P., Siebert, Gerhard A., Anissimov, Yuri G., Roberts, Michael S. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Gastrointestinal & Liver Physiology; Mar2003, Vol. 284 Issue 3, pG423, 11p, 1 Diagram, 3 Charts, 12 Graphs |
| Abstrakt: |
Disposition kinetics of [³H] palmitate and its low-molecular-weight metabotites 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 palmitare, 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 LFABP levels. It is concluded that the variability in hepatic pharmacokinetics of unchanged [³H]palmitate and its lowmolecular-weight metabolites in perfused rat livers is related to levels of L-FABP and not those of other intrahepatic proteins. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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