Uptake of a protein-bound polar compound, acetaminophen sulfate, by perfused rat liver
| Autor: | K. Sandy Pang, Wendy F. Cherry, Ford Barker, Glen G. Bach, Carl A. Goresky, Andreas J. Schwab |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Male
Radioisotope Dilution Technique medicine.medical_specialty Sucrose Serum albumin Tritium Models Biological Iodine Radioisotopes chemistry.chemical_compound Pharmacokinetics Internal medicine medicine Animals Carbon Radioisotopes Serum Albumin Acetaminophen Hepatology biology Chemistry Liver cell digestive oral and skin physiology Albumin Biological Transport Rats Inbred Strains Venous blood Metabolism Chromium Radioisotopes Rats Perfusion Kinetics Endocrinology medicine.anatomical_structure Liver Hepatocyte biology.protein Mathematics Protein Binding |
| Zdroj: | Hepatology. 16:173-190 |
| ISSN: | 1527-3350 0270-9139 |
| DOI: | 10.1002/hep.1840160129 |
| Popis: | The hepatocytic entry of acetaminophen sulfate conjugate was examined in the rat liver, perfused with red cells with and without albumin, by use of the multiple-indicator dilution technique. [3H]acetaminophen sulfate was injected into the portal vein in a bolus of blood containing51Cr-labeled red blood cells (a vascular reference), sucrose (a low-molecular-weight interstitial reference) or125I-labeled albumin (a high-molecular-weight interstitial reference, included when albumin was present), and the time courses of their outflow into the hepatic venous blood were observed. The [3H]acetaminophen sulfate, which binds partially to albumin, emerged between albumin and sucrose in the presence of albumin, precessed the upslope of the sucrose curve and showed a late low-in-magnitude tailing; the precession disappeared in the absence of albumin. Biliary excretion of [3H]acetaminophen sulfate was less than 1% of the dose. Quantitative evaluation with a barrier-limited, spacedistributed variable transit time model (including rapidly equilibrating albumin binding) accounted for the albumin effect on [3H]acetaminophen sulfate behavior and demonstrated a low liver cell permeability for the acetaminophen sulfate and a small interstitial binding space for its nonalbumin-bound fraction in excess of that for sucrose, which in the absence of albumin was of similar dimensions. (HEPATOLOGY 1992;16:173–190.) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text