| Pharmacokinetic self-potentiation of idarubicin by induction of anthracycline carbonyl reducing enzymes. | |
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MedLine Citation:
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PMID: 18398750 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Severe myelosuppression is one of the major adverse effects of Idarubicin (IDA). Especially, after two sequential therapy courses, IDA showed a stronger myelosuppression than after the first course. IDA was metabolized in liver by carbonyl reducing enzymes (CRE) to its 13-OH metabolite, idarubicinol(IDAol),which is more active compared with IDA. RLN-B2, a rat liver cell line, precultured in the presence of IDA showed higher CRE activity compared with non-precultured cells. A crude extract of the enzyme obtained from the livers of F344 rats preadministered IDA 7 days before they were sacrificed showed higher enzymatic activity than that from non-preadministered rats. At 4 h after IDA i.v., the production of IDAol was facilitated in the preadministered group compared with the non-preadministered group. In conclusion, CRE was induced by IDA pretreatment in vitro and vivo, resulting in increased IDAol, which could cause self-potentiation of the myelosuppressive and probably antitumor effects of IDA. |
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Authors:
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Taro Yamashita; Toshihiro Fukushima; Takanori Ueda |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Leukemia & lymphoma Volume: 49 ISSN: 1029-2403 ISO Abbreviation: Leuk. Lymphoma Publication Date: 2008 Apr |
Date Detail:
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Created Date: 2008-04-09 Completed Date: 2008-08-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9007422 Medline TA: Leuk Lymphoma Country: England |
Other Details:
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Languages: eng Pagination: 809-14 Citation Subset: IM |
Affiliation:
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First Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alcohol Oxidoreductases
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genetics*,
metabolism Animals Anthracyclines Cell Line Gene Expression Regulation, Enzymologic / drug effects* Idarubicin / metabolism, pharmacokinetics* Liver / cytology, enzymology Pharmacokinetics Rats |
| Chemical | |
Reg. No./Substance:
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0/Anthracyclines; 58957-92-9/Idarubicin; EC 1.1.-/Alcohol Oxidoreductases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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