Document Detail


Carbapenem antibiotics inhibit valproic acid transport in Caco-2 cell monolayers.
MedLine Citation:
PMID:  11897429     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Mayumi Torii; Yoshiharu Takiguchi; Miyako Izumi; Tokuya Fukushima; Masayuki Yokota
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of pharmaceutics     Volume:  233     ISSN:  0378-5173     ISO Abbreviation:  Int J Pharm     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-03-18     Completed Date:  2002-04-09     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  7804127     Medline TA:  Int J Pharm     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  253-6     Citation Subset:  IM    
Affiliation:
Department of Clinical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505, Japan.
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MeSH Terms
Descriptor/Qualifier:
Anticonvulsants / 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:
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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