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Assessment and modulation of forsythiaside absorption with MDCKII cells and validation with in situ intestinal experiment.
MedLine Citation:
PMID:  22430364     Owner:  NLM     Status:  Publisher    
Forsythiaside was characterized by low intestinal absorption by in situ rat experiment and Caco-2 cells. The mechanisms behind this low absorption had not yet been elucidated. The purpose of this study was to investigate the role of efflux transporters in the intestinal absorption of forsythiaside as a potential mechanism for its low small-intestinal absorption following oral administration. Polarized MDCKII cell lines stably transfected with human or murine complementary DNA encoding for various efflux transporters (P-gp/MDR1, MRP2 and Bcrp1) were used to study transepithelial transport of forsythiaside and compare results with the MDCKII-Wild type cells. The transportation inhibitors GF120918, MK571 and Ko143 were used to investigate the transport mechanism. The active transport of forsythiaside was found in MDCKII-WT cells. The MDCKII-MRP2 and MDCKII-Bcrp1 cells significantly increased forsythiaside efflux ratio compared with the parental cells due to the apically directed transport by MRP2 and Bcrp1, respectively. The efflux ratios in MRP2 and Bcrp1 transfected cell lines were greatly decreased in the presence of MK-571 and Ko143, respectively, which indicated that forsythiaside efflux by MRP2 and Bcrp1 were significantly inhibited by their selective inhibitors. MDCKII-MDR1 cells did not exhibit a significant reduction in the forsythiaside efflux compared with the parental cells, indicating that it was not a good substrate for MDR1. And the results were then validated by the in situ experiment. This study presents direct evidence that forsythiaside is effluxed by both MRP2 and Bcrp1, which may contribute to its poor oral bioavailability.
Yun-Xia Li; Ruo-Qi Zhang; Cheng Peng
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-20
Journal Detail:
Title:  European journal of drug metabolism and pharmacokinetics     Volume:  -     ISSN:  0378-7966     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7608491     Medline TA:  Eur J Drug Metab Pharmacokinet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Pharmacy College, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Road, Chengdu, 610075, People's Republic of China.
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