| Presence and ex vivo formation of acridone in blood of patients routinely treated with carbamazepine: exploration of the 9-acridinecarboxaldehyde pathway. | |
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MedLine Citation:
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PMID: 21087114 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Carbamazepine (CBZ) is a useful anticonvulsive drug associated with rare severe adverse drug reactions. The physio-pathological mechanisms of these reactions are unknown although evidence of immunological activation has been reported. The ability of 9-acridinecarboxaldehyde, a CBZ metabolite, to interact with leukocyte constituents was demonstrated, and catabolism of this compound into acridine (AI) and acridone (AO) was observed in vitro. In this study, we have assessed ex vivo the role of the extra-hepatic 9-acridinecarboxaldehyde pathway in the metabolism of CBZ. First, we verified the presence of the terminal metabolites AI and AO in CBZ-treated patients. Then, we tested ex vivo the transformation of CBZ, epoxy CBZ, iminostilbene, and AI into AO in the blood of these patients. We observed no direct formation of hydroxylated CBZ metabolites in isolated blood, and CBZ did not react with blood cells. Conversely, we detected a dose-dependent transformation of epoxy CBZ, iminostilbene, and AI into AO with individual variations from patient to patient. AO might thus be considered as a metabolite of 9-acridinecarboxaldehyde that does not react with cells (detoxicant pathway) as well as a marker of the formation of toxic AI derivatives (toxicant pathway). |
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Authors:
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Olivier Mathieu; Olivier Dereure; Dominique Hillaire-Buys |
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Publication Detail:
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Type: Journal Article Date: 2010-11-18 |
Journal Detail:
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Title: Xenobiotica; the fate of foreign compounds in biological systems Volume: 41 ISSN: 1366-5928 ISO Abbreviation: Xenobiotica Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1306665 Medline TA: Xenobiotica Country: England |
Other Details:
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Languages: eng Pagination: 91-100 Citation Subset: IM |
Affiliation:
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CHRU Montpellier, Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital, Montpellier, F-34000 France; University of Montpellier 1, Faculty of Medicine, Montpellier, F-34000 France. |
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