Document Detail


Establishment of MDCKII Cell Monolayer with Metabolic Activity by CYP3A4 Transduced with Recombinant Adenovirus.
MedLine Citation:
PMID:  22892444     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
This study aims to establish an in vitro system that can assess intestinal first-pass metabolism of CYP3A4 substrate drugs using adenoviral transduction. Madin-Darby canine kidney II (MDCKII) cells were used as a model of intestinal epithelial cells. Recombinant adenovirus expressing green fluorescent protein (AdGFP) and CYP3A4 (AdCYP3A4) was used as vectors. On day 2 after seeding MDCKII cells onto semipermeable membrane, cells were infected with each adenovirus vector at various MOIs (multiplicities of infection) ranging from 0 to 200. On day 5, cell monolayers were used for drug transport study. The expression of GFP in monolayers of MDCKII cells transduced with AdGFP increased MOI-dependently and adenoviral infection showed no effect on the membrane permeability of drugs. The metabolite formation rate of midazolam, a CYP3A4 substrate, in the permeation process of a monolayer linearly increased with an increase in the MOI of AdCYP3A4. When the period that vectors and cells were located adjacent to each other was prolonged, the rate increased 2-fold compared with that calculated from a result with a monolayer obtained from a shorter period of adjacency. This study indicates that monolayers of MDCKII cells transduced with AdCYP3A4 have the potential to enable estimation of the first-pass metabolism by CYP3A4 in the intestinal absorption process.
Authors:
Makoto Kataoka; Yuki Terashima; Katsuhiko Mizuno; Yoshie Masaoka; Shinji Sakuma; Tsuyoshi Yokoi; Shinji Yamashita
Related Documents :
21409224 - Roles of copper chaperone for superoxide dismutase 1 and metallothionein in copper home...
21537954 - Analysis of arsenic metabolites in hepg2 and as3mt-transfected cells.
22431644 - Feline morbillivirus, a previously undescribed paramyxovirus associated with tubulointe...
7948594 - Cell damage in vitro following direct contact with fine particles of titanium, titanium...
11969534 - Influence of substrate microrelief on the fréedericksz transition in a thin nematic cell.
23950874 - Cmv-independent lysis of glioblastoma by ex vivo expanded/activated vδ1+ γδ t cells.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-14
Journal Detail:
Title:  Drug metabolism and pharmacokinetics     Volume:  -     ISSN:  1880-0920     ISO Abbreviation:  Drug Metab. Pharmacokinet.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-15     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 Pharmaceutical Sciences, Setsunan University.
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:  Comparison of pharmacokinetics between loxoprofen and its derivative with lower ulcerogenic activity...
Next Document:  MONITORING OF INOSINE MONOPHOSHATE DEHYDROGENASE ACTIVITY AND EXPRESSION DURING EARLY PERIOD OF A MY...