| Nitric oxide induced sinusoidal relaxation after a propranolol priming dose in the perfused rat liver reduces propranolol availability on subsequent dosing. | |
| | |
MedLine Citation:
|
PMID: 20659130 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
|
1. The present study sought to explain the mechanism leading to reduced availability of propranolol when given after a priming dose in the single-pass perfused rat liver. 2. Extracellular sucrose space (as a measure of sinusoidal relaxation) in perfused rat liver before and after propranolol or propranolol and N(G)-nitro-L-arginine methyl ester (L-NAME; nitric oxide (NO) synthase inhibitor) treatment were examined. The results showed that propranolol induces sinusoidal relaxation in the perfused liver and this effect could be abolished by NO synthase inhibitor L-NAME. 3. Two bolus injections of propranolol were given to the isolated perfused rat liver and outflow concentration-time profiles of intact propranolol were determined. A two-phase physiologically based organ pharmacokinetic model was applied to estimate hepatocellular influx, efflux, binding, ion-trapping and metabolic elimination pharmacokinetic parameters for propranolol. The recovery of propranolol in the second injection was approximately 54% of that in the first injection. The permeability-surface area product, the binding and the intrinsic clearance all increased significantly after prior exposure of the rat liver to the first bolus of propranolol (P < 0.05). 4. Based on the findings of the present study, we propose that the most likely explanation for the reduced availability of a second propranolol dose (after administration of a priming dose) in the perfused liver is a consequence of the NO-mediated sinusoidal relaxation effect of propranolol, arising from the priming dose. This observation supports the view that the pharmacokinetics of some drugs might be altered by the pharmacodynamic effects of the same drug given earlier in the perfused liver. |
| | |
Authors:
|
Xin Liu; Yuhong Zou; Alexander M Khlentzos; Yan Yang; Julijana Nikolovski; Michael Weiss; Michael S Roberts |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Clinical and experimental pharmacology & physiology Volume: 37 ISSN: 1440-1681 ISO Abbreviation: Clin. Exp. Pharmacol. Physiol. Publication Date: 2010 Oct |
Date Detail:
|
Created Date: 2010-10-29 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0425076 Medline TA: Clin Exp Pharmacol Physiol Country: Australia |
Other Details:
|
Languages: eng Pagination: 1028-33 Citation Subset: IM |
Copyright Information:
|
© 2010 The Authors. Clinical and Experimental Pharmacology and Physiology © 2010 Blackwell Publishing Asia Pty Ltd. |
Affiliation:
|
Therapeutics Research Centre, School of Medicine, University of Queensland, Brisbane, Qld, Australia. |
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: Feasibility of high-density electrophysiological study using multiple-electrode array in isolated sm...
Next Document: Protective effects of lithium treatment for spatial memory deficits induced by tau hyperphosphorylat...