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    
Abstract/OtherAbstract:
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.
Authors:
Sho Wada; Takashi Kano; Suzune Mita; Yoko Idota; Kaori Morimoto; Fumiyoshi Yamashita; Takuo Ogihara
Related Documents :
12891489 - Low-fat diet impairs postresection intestinal adaptation in a rat model of short bowel ...
7373489 - Intestinal loop lengthening--a technique for increasing small intestinal length.
1706669 - Distributional change of achromatic epithelial cells of the intestine in the fetuses an...
3688229 - Effect of chloroquine on intestinal lipid metabolism.
6131789 - Stimulatory effect of short chain fatty acids on the epithelial cell proliferation in r...
2597179 - Metabolism of n-acetyl-l-cysteine. some structural requirements for the deacetylation a...
21842269 - Profile of nucleotide catabolism and ectonucleotidase expression from the hippocampi of...
3550529 - Regrowth of lesioned dorsal root nerve fibers into the spinal cord of neonatal rats.
21787199 - Ultrasound enhances the healing of orthodontically induced root resorption in rats.
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:  -    
Affiliation:
Faculty of Pharmacy, Takasaki University of Health and Welfare.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

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


Previous Document:  Flow cytometry analysis of cancer cell death induced by the extract of Thai plant <i>Ellipeiopsis ch...
Next Document:  Effects of grapefruit juice and <i>SLCO1B1</i> 388A>G polymorphism on the pharmacokinetics of pitava...