title: Uptake of a protein-bound polar compound, acetaminophen sulfate, by perfused rat liver.
abstract: 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 containing 51Cr-labeled red blood cells (a vascular reference), sucrose (a low-molecular-weight interstitial reference) or 125I-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, processed 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, space-distributed 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.
authors.affiliation: McGill University Medical Clinic, Montreal General Hospital, Quebec, Canada.
authors.forename: C A
authors.initials: CA
authors.lastname: Goresky
authors.forename: K S
authors.initials: KS
authors.lastname: Pang
authors.forename: A J
authors.initials: AJ
authors.lastname: Schwab
authors.forename: F
authors.initials: F
authors.lastname: Barker
authors.forename: W F
authors.initials: WF
authors.lastname: Cherry
authors.forename: G G
authors.initials: GG
authors.lastname: Bach
mesh_terms: D000082:Acetaminophen / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002250:Carbon Radioisotopes; D002860:Chromium Radioisotopes; D007457:Iodine Radioisotopes; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008433:Mathematics; D008954:Models, Biological; D010477:Perfusion; D011485:Protein Binding; D011865:Radioisotope Dilution Technique; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000302:isolation & purification / Q000378:metabolism*; D014316:Tritium
chemical_list: D002250:Carbon Radioisotopes; D002860:Chromium Radioisotopes; D007457:Iodine Radioisotopes; D012709:Serum Albumin; D014316:Tritium; D000082:Acetaminophen; C045667:acetaminophen sulfate ester