| Effects of albumin on the disposition of morphine and morphine-3-glucuronide in the rat isolated perfused liver. | |
| | |
MedLine Citation:
|
PMID: 9075586 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
1. The effect of albumin on the disposition of morphine and hepatically generated morphine-3-glucuronide (M3G) was investigated in the single-pass rat isolated perfused liver. 2. Using a balanced cross-over design, each of 10 livers was perfused at 30 mL/min with medium containing 2.7 mumol/L morphine in the presence and absence of 10 g/L bovine serum albumin (BSA). 3. Both bile flow rate and hepatic oxygen consumption were significantly higher (P < 0.005) when BSA was present in the perfusion medium, suggestive of a change in the functional performance of the perfused liver. 4. The binding of morphine and M3G was negligible in both BSA-free and -containing perfusate. 5. Outflow perfusate contained both morphine and M3G, while the metabolite but not morphine was found in bile. The recovery of the administered morphine was approximately 100% and was not altered (P > 0.05) by the presence or absence of BSA. 6. The fraction of morphine escaping heptic extraction in the absence of BSA (mean +/- SD; 0.41 +/- 0.14) was not altered significantly (P > 0.05) by the presence of the protein in perfusate (0.35 +/- 0.13), indicating no change in the intrinsic clearance or morphine despite the difference in oxygen consumption. 7. The fraction of hepatically generated M3G excreted in bile was significantly higher (P < 0.005) when BSA was present in the perfusate than when it was not (0.44 +/- 0.14 vs 0.38 +/- 0.16, respectively). 8. The results are consistent with the concept that BSA modifies the ability of solutes, including M3G, to move through the paracellular pathway from the canalicular to the vascular space. 9. It is concluded that because albumin may modify not only the unbound fraction of a ligand in perfusate, but also the functional performance of the liver, care is needed in the interpretation of studies examining the influence of the protein on the hepatic disposition of drugs and their metabolites. |
| | |
Authors:
|
J A O'Brien; A M Evans; R L Nation |
Related Documents
:
|
5256 - Uptake and disposition of chlorinated biphenyls by isolated perfused rat liver. 9352876 - Effect of fasting on the uptake of bilirubin and sulfobromophthalein by the isolated pe... 4056346 - Reduction of the increased portal vascular resistance of the isolated perfused cirrhoti... 17910026 - Quantitative atp synthesis in human liver measured by localized 31p spectroscopy using ... 3432946 - Proliferative exocrine pancreatic lesions in rats. the effect of sample size on the inc... 16984956 - Use of a pharmacokinetic-driven computational fluid dynamics model to predict nasal ext... |
Publication Detail:
|
Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Clinical and experimental pharmacology & physiology Volume: 24 ISSN: 0305-1870 ISO Abbreviation: Clin. Exp. Pharmacol. Physiol. Publication Date: 1997 Feb |
Date Detail:
|
Created Date: 1997-06-02 Completed Date: 1997-06-02 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0425076 Medline TA: Clin Exp Pharmacol Physiol Country: AUSTRALIA |
Other Details:
|
Languages: eng Pagination: 143-8 Citation Subset: IM |
Affiliation:
|
Centre for Pharmaceutical Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cross-Over Studies Female Liver / drug effects*, metabolism* Longitudinal Studies Morphine / pharmacokinetics* Morphine Derivatives / pharmacokinetics* Perfusion Protein Binding / drug effects Rats Rats, Sprague-Dawley Serum Albumin, Bovine / pharmacology* |
| Chemical | |
Reg. No./Substance:
|
0/Morphine Derivatives; 0/Serum Albumin, Bovine; 20290-09-9/morphine-3-glucuronide; 57-27-2/Morphine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Hypotensive effect of chronically infused adrenomedullin in conscious Wistar-Kyoto and spontaneously...
Next Document: Effect of NG-monomethyl-L-arginine on the microcirculation of rat skin.