Document Detail

Transepithelial transport of telmisartan in caco-2 monolayers.
MedLine Citation:
PMID:  16327156     Owner:  NLM     Status:  MEDLINE    
Telmisartan is the most recently marketed angiotensin II type 1 receptor antagonist. Drug-drug interactions involving transporters can directly affect the therapeutic safety and efficacy of many important drugs. In clinical practice, telmisartan is coadministered with many kinds of drugs. However, little is known about the contribution of transporters to the intestinal transport of telmisartan. The aim of this study was to determine the transport mechanism of telmisartan across intestinal epithelial cells. In the presence of an inwardly directed proton gradient, the apical-to-basal transport of telmisartan was greater than basal-to-apical transport. Thus, we focused on the uptake mechanism of telmisartan across brush-border membranes. The uptake of telmisartan by Caco-2 cells was shown to be energy- and proton-dependent. Although some monocarboxylates inhibited the uptake of telmisartan, L-lactic acid, which is a typical substrate of the monocarboxylate transporter (MCT) 1-MCT4, did not affect the uptake of telmisartan. Preloading of acetic acid enhanced the uptake of telmisartan, showing a trans-stimulation effect. These results suggest that the carrier-mediated transport system is involved in the uptake of telmisartan by Caco-2 cells and that the apical-localized transport system is similar to MCTs, but not MCT1-MCT4. It is possible that telmisartan reduce the absorption of coadministered drugs by sharing the MCTs. Since MCTs have an important role in the intestinal absorption of pharmacologically active compounds, it is important to be aware of the potential of telmisartan-drug interactions involving MCTs and to act in order to prevent undesirable and harmful consequences.
Yoshikazu Goto; Shirou Itagaki; Shinichiro Umeda; Masaki Kobayashi; Takeshi Hirano; Ken Iseki; Koji Tadano
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  28     ISSN:  0918-6158     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-12-05     Completed Date:  2006-03-09     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  2235-9     Citation Subset:  IM    
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MeSH Terms
Angiotensin II Type 1 Receptor Blockers / antagonists & inhibitors,  metabolism,  pharmacology*
Benzimidazoles / antagonists & inhibitors,  metabolism,  pharmacology*
Benzoates / antagonists & inhibitors,  metabolism,  pharmacology*
Biological Transport / drug effects
Caco-2 Cells / drug effects,  metabolism*,  pathology
Dose-Response Relationship, Drug
Epithelium / drug effects*,  metabolism*,  pathology
Hydrogen-Ion Concentration
Monocarboxylic Acid Transporters / pharmacology
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Benzimidazoles; 0/Benzoates; 0/Monocarboxylic Acid Transporters; U5SYW473RQ/telmisartan

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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