| Characterization of oxalic acid derivatives as new metabolites of metamizol (dipyrone) in incubated hen's egg and human. | |
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MedLine Citation:
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PMID: 16417995 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Metamizol (dipyrone, 1), a widely used drug with effective analgesic and antispasmodic properties, shows severe side effects like agranulocytosis and anaphylactic shock reactions, the reasons of which are not known until today. After oral administration 1 is completely metabolized. All hitherto known metabolites have an intact pyrazolinone ring structure like the parent compound and are completely extractable from urine with polar organic solvents. However, only a fractional amount of the applied dosage can be recovered by this procedure. To clarify the reason of this deficit of unknown metabolites we followed the hypothesis of oxidative rupture of the heterocyclic ring during metabolism of 1. On the basis of former in vitro results we now were able to identify in quality three oxalic acid derivatives and one acetic acid phenylhydrazide as new metabolites of metamizol in the allantoic fluid (AF) of incubated hen's eggs as well as in human urine by means of GC-MS analysis and comparison with unequivocally synthesized authentic reference compounds. Whereas the oxamazide 7, the phenylhydrazide 8 and N-methyloxamic acid 9 are only present in trace concentrations and therefore cannot account for the deficit in the balance of metabolites, the oxalic acid monohydrazide 11 seems to be excreted in higher amount. But quantitative determination of this new metabolite would be required to answer the open questions concerning the biotransformation of metamizol and thereby to detect new facts about mode of action and side effects of this drug. |
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Authors:
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Julia C Wessel; Magdalena Matyja; Michael Neugebauer; Heiko Kiefer; Thomas Daldrup; Fuad A Tarbah; Horst Weber |
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Publication Detail:
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Type: Journal Article Date: 2006-01-18 |
Journal Detail:
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Title: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences Volume: 28 ISSN: 0928-0987 ISO Abbreviation: Eur J Pharm Sci Publication Date: 2006 May |
Date Detail:
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Created Date: 2006-03-14 Completed Date: 2006-06-14 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9317982 Medline TA: Eur J Pharm Sci Country: Netherlands |
Other Details:
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Languages: eng Pagination: 15-25 Citation Subset: IM |
Affiliation:
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Institut für Pharmazeutische und Medizinische Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Animals Anti-Inflammatory Agents, Non-Steroidal / metabolism* Biotransformation Chickens Dipyrone / metabolism* Eggs / analysis Esters / chemistry, metabolism Female Gas Chromatography-Mass Spectrometry Humans Hydrolysis Indicators and Reagents Magnetic Resonance Spectroscopy Male Methylation Oxalates / chemistry* Rats |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents, Non-Steroidal; 0/Esters; 0/Indicators and Reagents; 0/Oxalates; 68-89-3/Dipyrone |
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