| Membrane permeability and lipophilicity in the isolated perfused rat liver: 5-ethyl barbituric acid and other compounds. | |
| | |
MedLine Citation:
|
PMID: 7473185 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The distribution kinetics of 5-ethyl barbituric acid (EBA) has been examined in the rat liver. The isolated in situ liver (n = 4) was perfused at a constant rate (15.1 +/- 0.2 ml/min, mean +/- S.D.) with protein-free Krebs bicarbonate medium in a single-pass mode. [14C]Sucrose (extracellular reference) and [14C]EBA were injected separately as bolus doses into the portal vein. The outflow data were analyzed using the axial dispersion model. The one-compartment dispersion model adequately described the data for sucrose, with a dispersion number (DN) of 0.25 +/- 0.04 and a volume of distribution (VH) of 0.14 +/- 0.01 ml/g liver. The two-compartment dispersion model, which incorporates a cellular permeability barrier, provided a better description of the EBA outflow data. The estimated VH, influx and efflux rate constants and permeability-surface area product (PS) for EBA were 0.37 +/- 0.04 ml/g liver, 0.028 +/- 0.004 sec-1, 0.019 +/- 0.001 sec-1 and 3.4 +/- 0.5 ml/min, respectively. Despite low hepatocyte membrane permeability, the DN value for EBA (0.28 +/- 0.03) was not significantly different from that of sucrose, which supports the concept that dispersion of compounds in the liver is primarily determined by the heterogeneity of the hepatic microvasculature. The relationship between PS values in the perfused rat liver (either abstracted or taken from the literature data) and physicochemical properties for 17 compounds has been explored. There appears to be a continuous relationship between PS and logD, a measure of lipophilicity that takes into account the degree of ionization in the perfusate. The PS value for EBA is close to that expected based on its physicochemical properties. |
| | |
Authors:
|
C Chou; A J McLachlan; M Rowland |
Related Documents
:
|
12215655 - A physiologically based pharmacokinetic model for trichloroethylene in the male long-ev... 8897845 - Contribution of mitochondrial proton leak to skeletal muscle respiration and to standar... 2268905 - Salivary excretion of 5-fluorouracil (5-fu). v. effect of 5-fu concentration in perfusa... 9435315 - Evidence for sodium-dependent active urea secretion in the deepest subsegment of the ra... 9800685 - Purification and characterization of 38-kda protein in plasma of dietary magnesium-defi... 15261985 - New data on biological effects of chlorhexidine: fe2+ induced lipid peroxidation and mi... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: The Journal of pharmacology and experimental therapeutics Volume: 275 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 1995 Nov |
Date Detail:
|
Created Date: 1995-12-19 Completed Date: 1995-12-19 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 933-40 Citation Subset: IM |
Affiliation:
|
Department of Pharmacy, University of Manchester, United Kingdom. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Barbiturates / chemistry, metabolism* Capillary Permeability Kinetics Liver / chemistry, metabolism* Male Models, Theoretical Rats Rats, Sprague-Dawley Solubility |
| Chemical | |
Reg. No./Substance:
|
0/Barbiturates |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Peritubular paraquat transport in isolated renal proximal tubules.
Next Document: Pretreatment with a blocking monoclonal antibody to P-selectin accelerates pharmacological thromboly...