| Hepatic disposition of fexofenadine: influence of the transport inhibitors erythromycin and dibromosulphothalein. | |
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MedLine Citation:
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PMID: 11303961 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: To examine the disposition of fexofenadine in the isolated perfused rat liver and the influence of erythromycin and dibromosulphthalein (DBSP) on the hepatic uptake and biliary excretion of fexofenadine. METHODS: Livers from four groups of rats were perfused in a recirculatory manner with fexofenadine HCl added as a bolus (125, 250, 500, or 1000 microg) to perfusate. Livers from another three groups of rats were perfused with 250 microg of fexofenadine HCl. With one group as control, erythromycin (4.0 microg/ml) or DBSP (136 microg/ml) was added to the perfusate of the other groups. In all experiments, perfusate and bile were collected for 60 min; in addition, livers from the second experiment were retained for assay. Fexofenadine was determined in perfusate, bile, and homogenized liver by HPLC. RESULTS: The area under the curve (AUC) of fexofenadine was linearly related to concentration. It was unchanged from control (12,800 +/- 200 ng x h/ml) by erythromycin (14,400 +/- 2000 ng x h/ml), but was increased 95% by DBSP (25,000 +/- 2600 ng x h/ml, P <0.001). The ratios of the concentrations of fexofenadine in liver/perfusate were decreased significantly by DBSP; those for bile/liver were increased by erythromycin. CONCLUSIONS: Erythromycin reduced the canalicular transport of fexofenadine into bile, whereas DBSP reduced uptake across the sinusoidal membrane. |
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Authors:
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R W Milne; L A Larsen; K L Jørgensen; J Bastlund; G R Stretch; A M Evans |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Pharmaceutical research Volume: 17 ISSN: 0724-8741 ISO Abbreviation: Pharm. Res. Publication Date: 2000 Dec |
Date Detail:
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Created Date: 2001-04-16 Completed Date: 2001-07-12 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8406521 Medline TA: Pharm Res Country: United States |
Other Details:
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Languages: eng Pagination: 1511-5 Citation Subset: IM |
Affiliation:
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Centre for Pharmaceutical Research, School of Pharmacy and Medical Science, University of South Australia, Adelaide, Australia. robert.milne@unisa.edu.au |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Area Under Curve Bile / drug effects, metabolism Biological Transport, Active / drug effects Erythromycin / pharmacology* Histamine H1 Antagonists / pharmacokinetics* Liver / drug effects, metabolism* Male Protein Synthesis Inhibitors / pharmacology* Rats Rats, Sprague-Dawley Sulfobromophthalein / metabolism* Terfenadine / analogs & derivatives*, pharmacokinetics* |
| Chemical | |
Reg. No./Substance:
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0/Histamine H1 Antagonists; 0/Protein Synthesis Inhibitors; 114-07-8/Erythromycin; 138452-21-8/fexofenadine; 17199-35-8/dibromosulphthalein; 297-83-6/Sulfobromophthalein; 50679-08-8/Terfenadine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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