| Pharmacokinetic analysis and anticonvulsant activity of two polyesteric prodrugs of valproic acid. | |
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MedLine Citation:
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PMID: 8427944 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The pharmacokinetics of the following two polyesteric prodrugs of valproic acid (VPA) have been investigated: 1,4-butanediol divalproate (BDV) and glyceryl trivalproate (GTV). In addition, the anticonvulsant activity of these compounds has been evaluated and compared to that of VPA and valpromide (VPD). Valproic acid, and its two esteric derivatives were administered intravenously to six dogs at an equivalent dose (400 mg VPA) and their pharmacokinetics investigated. In the case of BDV, the biotransformation to VPA was complete, but in the case of GTV, it was only partial. Of the two investigated esteric prodrugs of VPA, only BDV demonstrated anticonvulsant activity and showed less neurotoxicity than VPA and VPD, and therefore had a better protective index. The anticonvulsant activity is explained on pharmacokinetic and pharmacodynamic grounds due to its complete conversion to VPA and the possible synergism in anticonvulsant activity between VPA and 1,4-butanediol. |
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Authors:
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S Hadad; T B Vree; E van der Kleijn; M Bialer |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biopharmaceutics & drug disposition Volume: 14 ISSN: 0142-2782 ISO Abbreviation: Biopharm Drug Dispos Publication Date: 1993 Jan |
Date Detail:
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Created Date: 1993-03-08 Completed Date: 1993-03-08 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7911226 Medline TA: Biopharm Drug Dispos Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 51-9 Citation Subset: IM |
Affiliation:
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Department of Pharmacy, School of Pharmacy, Hebrew University of Jerusalem, Israel. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anticonvulsants / pharmacokinetics*, pharmacology Butylene Glycols / pharmacokinetics*, pharmacology Dogs Drug Evaluation, Preclinical Female Male Molecular Structure Prodrugs / pharmacokinetics*, pharmacology Random Allocation Triglycerides / pharmacokinetics*, pharmacology Valproic Acid / analogs & derivatives*, pharmacokinetics, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Anticonvulsants; 0/Butylene Glycols; 0/Prodrugs; 0/Triglycerides; 146356-76-5/glyceryl trivalproate; 77656-73-6/1,4-butanediol divalproate; 99-66-1/Valproic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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