| Poloxamer 407 increases the recovery of paracetamol in the isolated perfused rat liver. | |
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MedLine Citation:
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PMID: 20564335 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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Sarah J Mitchell; Aniko Huizer-Pajkos; Victoria C Cogger; Andrew J McLachlan; David G Le Couteur; Sarah N Hilmer |
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Publication Detail:
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Type: Journal Article Date: 2010-06-16 |
Journal Detail:
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Title: Journal of pharmaceutical sciences Volume: 100 ISSN: 1520-6017 ISO Abbreviation: J Pharm Sci Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985195R Medline TA: J Pharm Sci Country: United States |
Other Details:
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Languages: eng Pagination: 334-40 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Wiley-Liss, Inc. |
Affiliation:
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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. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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