Document Detail


Poloxamer 407 increases the recovery of paracetamol in the isolated perfused rat liver.
MedLine Citation:
PMID:  20564335     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The role of the fenestrated liver sinusoidal endothelial cells (LSECs) in the hepatic disposition of paracetamol was investigated in isolated perfused livers from rats treated with poloxamer 407 (P407), a surfactant that causes extensive defenestration of the LSECs. Bolus doses containing tracer amounts of (14) C-paracetamol and reference markers (Evans Blue, (3) H-sucrose) were injected into control rats and rats that had been administered P407 via intra-peritoneal injection 24 h prior to experimentation. Scanning electron microscopy confirmed a reduced number of fenestrations in rats treated with P407. The recovery of paracetamol was significantly increased in P407 rats compared to controls (0.72 ± 0.07 P407 vs. 0.67 ± 0.04 control, p < 0.05) and the volume of distribution of paracetamol as a fraction of the sucrose volume was significantly reduced. The permeability-surface area (PS) product for the transfer of paracetamol across the LSECs was also reduced in the P407 rats (0.032 ± 0.009 P407 vs. 0.043 ± 0.007 mL/s/g controls, p < 0.05). P407 treatment resulted in increased recovery and decreased PS product of paracetamol following a single pass through the isolated perfused liver. This is consistent with exclusion of paracetamol from the space of Disse due to defenestration of the LSECs. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:334-340, 2011.
Authors:
Sarah J Mitchell; Aniko Huizer-Pajkos; Victoria C Cogger; Andrew J McLachlan; David G Le Couteur; Sarah N Hilmer
Related Documents :
3942135 - Differential responsiveness of proximal tubule segments to metabolic inhibitors in the ...
7191095 - Influence of aldosterone on epithelial leakiness of rat proximal tubules. microconducti...
209115 - Catabolism of the apoprotein of low density lipoproteins by the isolated perfused rat l...
2143535 - Nonlinear elimination kinetics of 5-fluoro-2'-deoxyuridine in isolated perfused rat liv...
1987305 - Intrinsic vasodilation protects wistar kyoto rats from progressive glomerulosclerosis a...
9194125 - Relationship between time-resolved and non-time-resolved beer-lambert law in turbid media.
Publication Detail:
Type:  Journal Article     Date:  2010-06-16
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  100     ISSN:  1520-6017     ISO Abbreviation:  J Pharm Sci     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  334-40     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Wiley-Liss, Inc.
Affiliation:
Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital, St Leonards, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Laboratory of Ageing and Pharmacology, Kolling Institute and Royal North Shore Hospital, St Leonards, NSW, Australia. smitchell@med.usyd.edu.au.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  What is the minimum number of water molecules required to dissolve a potassium chloride molecule?
Next Document:  Relative bioavailability of three different solid forms of PNU-141659 as determined with the artific...