| Alterations in the renal excretion of valproate and its metabolites after chronic treatment. | |
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MedLine Citation:
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PMID: 1985825 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Urinary excretion of valproate (VPA, administered as its sodium salt) and its various metabolites was studied in rats before and after 6 weeks of chronic treatment with intraperitoneal (i.p.) injection of 200 mg/kg VPA three times daily. Urinary excretion was determined after i.p. injection of a single dose of 200 mg/kg VPA, to which [14C]labeled VPA had been added to yield a dose of 1 microCi/kg body weight. Unlabeled VPA and metabolites were determined in urine by gas chromatography-mass spectrometry (GC-MS). After injection of a single dose of VPA before onset of chronic treatment, approximately 40-50% of the dose administered was excreted in the urine within 24 h, mainly in the form of conjugated VPA and omega-oxidation products, i.e., 5-hydroxy-VPA and 2-propyl-glutaric acid. After chronic treatment, urinary excretion of total radioactivity increased approximately 75% as compared with activity before chronic treatment, demonstrating a marked increase in elimination rate of VPA during prolonged administration. Determination of VPA and metabolites in urine by GC-MS indicated that this enhanced elimination resulted mainly from increases in glucuronidation and beta-oxidation of VPA, whereas omega-oxidation was apparently not altered or was even reduced. The data strongly indicate that at least in rats VPA produces induction of its own metabolism during prolonged treatment. |
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Authors:
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J E Fisher; H Nau; W Löscher |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Epilepsia Volume: 32 ISSN: 0013-9580 ISO Abbreviation: Epilepsia Publication Date: 1991 Jan-Feb |
Date Detail:
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Created Date: 1991-02-11 Completed Date: 1991-02-11 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2983306R Medline TA: Epilepsia Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 146-50 Citation Subset: IM |
Affiliation:
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Institute of Toxicology and Embryopharmacology, Free University of Berlin, F.R.G. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arylsulfatases / metabolism Biotransformation Carbon Radioisotopes Enzyme Induction Female Gas Chromatography-Mass Spectrometry Glucuronidase / metabolism Injections, Intraperitoneal Rats Rats, Inbred Strains Valproic Acid / administration & dosage, metabolism, urine* |
| Chemical | |
Reg. No./Substance:
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0/Carbon Radioisotopes; 99-66-1/Valproic Acid; EC 3.1.6.1/Arylsulfatases; EC 3.2.1.31/Glucuronidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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