Abstract:
:We examine the pharmacokinetic profile of cyclosporin A (CyA) after intravenous administration to rats prepared as models of various disease states found in patients who receive organ transplantations. After intravenous bolus administration to normal rats, the total blood clearance (CLt) of CyA showed a dose-dependent increase. The CLt was reduced in anemic (ANE) rats prepared by venesection, in carbon tetrachloride-induced acute hepatic failure (AHF) rats, and in glycerol-induced acute renal failure (ARF) rats. On the other hand, the volume of distribution at a steady state (Vss) of CyA increased significantly in ANE and aged (AGE) rats. CyA distribution was tissue-specific, and the tissue CyA concentration was disease state-dependent. Linear relationships between the CyA concentration in whole blood and various tissues (liver, kidney and heart) were found in AGE, ANE and AHF animals. However, in ARF rats, tissue concentration was not increased to a great extent in comparison with the other disease models, even though the whole blood CyA concentration was increased. The tissue per blood concentration ratio (Kb), which represented the CyA tissue transfer from systemic circulation, was influenced by the disease state. In the liver, in particular, the Kb increased in the AHF and AGE groups, whereas it decreased in the ANE and ARF rats. The CLt of CyA was negatively related to the erythrocyte per plasma concentration ratio (E/P), and the E/P exhibited disease state-dependent changes, suggesting that this ratio is a valuable indicator for predicting variations in CyA total blood clearance in organ transplant patients during episodes of anemia, nephrotoxicity and hepatotoxicity.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Shibata N,Shimakawa H,Minouchi T,Yamaji Adoi
10.1248/bpb.16.1130subject
Has Abstractpub_date
1993-11-01 00:00:00pages
1130-5issue
11eissn
0918-6158issn
1347-5215journal_volume
16pub_type
杂志文章abstract::The constituents of the stem bark of Garcinia subelliptica (Guttiferae) were investigated based on its trypanocidal activity against epimastigotes of Trypanosoma cruzi, the etiologic agent for Chagas' disease. As the active components, nine xanthones were isolated including two new ones, 4-hydroxybrasilixanthone B and...
journal_title:Biological & pharmaceutical bulletin
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
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journal_title:Biological & pharmaceutical bulletin
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pub_type: 临床试验,杂志文章
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章,评审
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.22.132
更新日期:1999-02-01 00:00:00
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pub_type: 临床试验,杂志文章
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:1996-03-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
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更新日期:2012-01-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
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更新日期:2006-01-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:2001-03-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:1994-07-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b12-00875
更新日期:2013-01-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
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更新日期:2004-12-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
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更新日期:1993-04-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:1998-03-01 00:00:00
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journal_title:Biological & pharmaceutical bulletin
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journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
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更新日期:1997-07-01 00:00:00