Document Detail

Role of inter-segmental differences in P-glycoprotein expression and activity along rat small intestine in causing double-peak phenomena of substrate plasma concentration.
MedLine Citation:
PMID:  22850759     Owner:  NLM     Status:  Publisher    
Conflicting results have been reported on segmental differences in expression of P-glycoprotein (P-gp) along the small intestine of animals and humans. In this study, we investigated P-gp mRNA and protein levels within each of nine segments of rat small intestine. In addition, P-gp activity in each segment was evaluated in terms of permeability of Rhodamine123 (Rho123), a typical P-gp substrate, using the serial intestinal non-everted sac method. The P-gp mRNA levels tended to increase from the duodenum to the ileum, with peaks in the upper and lower ileum, while P-gp protein level indicated maximum in the middle ileum. The activity of P-gp was also the highest in the middle ileum, and was highly correlated with P-gp protein level. The double-peaked plasma concentration profile that was observed following oral administration of Rho123 to rats could be well reproduced by an intestinal compartmental kinetic model incorporating inter-segmental differences of absorption and excretion rate constants. Our results suggest that the heterogeneous distribution of P-gp along the small intestine plays a key role in causing the double-peak of plasma concentration of P-gp substrates following oral administration to rats.
Sho Wada; Takashi Kano; Suzune Mita; Yoko Idota; Kaori Morimoto; Fumiyoshi Yamashita; Takuo Ogihara
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-31
Journal Detail:
Title:  Drug metabolism and pharmacokinetics     Volume:  -     ISSN:  1880-0920     ISO Abbreviation:  Drug Metab. Pharmacokinet.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-8-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101164773     Medline TA:  Drug Metab Pharmacokinet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Faculty of Pharmacy, Takasaki University of Health and Welfare.
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