| Carbapenem antibiotics inhibit valproic acid transport in Caco-2 cell monolayers. | |
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MedLine Citation:
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PMID: 11897429 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The concomitant use of carbapenem antibiotics with valproic acid has been prohibited because carbapenems induced a decrease in plasma concentration of valproic acid in epileptic patients during valproic acid therapy. Our previous in vivo study in rats proposed that inhibition by carbapenem of the intestinal absorption of valproic acid might be a possible mechanism for the drug-drug interaction. To demonstrate the hypothesis, we examined the effects of imipenem and panipenem on intestinal transepithelial transport of valproic acid using Caco-2 cell monolayers. Imipenem and panipenem inhibited the transport of [14C]-valproic acid across the Caco-2 cell monolayers from apical-to-basolateral side in a concentration-dependent manner, although they had no effect on the uptake of [14C]-valproic acid by Caco-2 cells. The inhibition by the carbapenems of the valproic acid transport was found even when they were added to only the basolateral side. From these results, the carbapenems may inhibit the absorption of valproic acid at the basolateral membrane of intestinal epithelial cells, which contributes to the decrease in plasma concentration of valproic acid after oral administration. |
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Authors:
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Mayumi Torii; Yoshiharu Takiguchi; Miyako Izumi; Tokuya Fukushima; Masayuki Yokota |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: International journal of pharmaceutics Volume: 233 ISSN: 0378-5173 ISO Abbreviation: Int J Pharm Publication Date: 2002 Feb |
Date Detail:
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Created Date: 2002-03-18 Completed Date: 2002-04-09 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 7804127 Medline TA: Int J Pharm Country: Netherlands |
Other Details:
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Languages: eng Pagination: 253-6 Citation Subset: IM |
Affiliation:
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Department of Clinical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anticonvulsants
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antagonists & inhibitors,
pharmacokinetics Biological Transport / drug effects Caco-2 Cells / drug effects, metabolism* Carbapenems / pharmacology* Humans Intestinal Mucosa / drug effects, metabolism Valproic Acid / antagonists & inhibitors, pharmacokinetics* |
| Chemical | |
Reg. No./Substance:
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0/Anticonvulsants; 0/Carbapenems; 99-66-1/Valproic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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