| Hepatic disposition of cyclosporine A in isolated perfused rat livers. | |
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MedLine Citation:
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PMID: 15144734 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: To develop an isolated perfused rat liver model to study the hepatic disposition of cyclosporine A (CyA) in both sexes. METHODS: Livers were isolated from male (n = 6) and female (n = 7) rats and perfused with a physiological buffer in a single-pass manner. A bolus 1-mg dose of CyA was injected into the inlet catheter and periodical samples (0-15 min) were collected from the outlet perfusate. The concentrations of CyA in the outlet perfusate, collected bile (0-15 min), and liver tissue (at the end of perfusion) were quantitated by HPLC and subjected to statistical moment analysis. RESULTS: The dilution curves of CyA in the outlet perfusate exhibited unusually long terminal phases due to large volume of distribution of the drug (approximately 100 mL/g) and its slow release from binding sites in the liver (net release rate constant of approximately 0.020 min(-1)). This was in contrast to the rapid uptake of the drug, indicated by significant amounts of the intact drug (>40%) taken up during one single pass through the liver. Consequently, the liver tissue:perfusate distribution ratio of CyA was very high (approximately 220). No significant differences were found between the male and female livers in any of the estimated parameters. CONCLUSIONS: The tissue binding of cyclosporine A is substantial, slowly reversible, and gender-independent in isolated perfused rat livers. |
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Authors:
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Reza Mehvar; Anjaneya P Chimalakonda |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't Date: 2004-02-17 |
Journal Detail:
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Title: Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Soci?t? canadienne des sciences pharmaceutiques Volume: 7 ISSN: 1482-1826 ISO Abbreviation: J Pharm Pharm Sci Publication Date: 2004 Feb |
Date Detail:
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Created Date: 2004-05-17 Completed Date: 2004-06-30 Revised Date: 2010-03-24 |
Medline Journal Info:
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Nlm Unique ID: 9807281 Medline TA: J Pharm Pharm Sci Country: Canada |
Other Details:
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Languages: eng Pagination: 47-54 Citation Subset: IM |
Affiliation:
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School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas 79106, USA. reza.mehvar@ttuhsc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chromatography, High Pressure Liquid Cyclosporine / pharmacokinetics* Female Immunosuppressive Agents / pharmacokinetics Liver / metabolism* Male Perfusion Rats Rats, Sprague-Dawley Sex Factors |
| Chemical | |
Reg. No./Substance:
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0/Immunosuppressive Agents; 59865-13-3/Cyclosporine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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