Abstract:
PURPOSE:Stable transformants expressing human multidrug resistance 1 (MDR1), monkey MDR1, canine MDR1, rat MDR1a, rat MDR1b, mouse mdr1a, and mouse mdr1b in LLC-PK1 were established to investigate species differences in P-glycoprotein (P-gp, ABCB1) mediated efflux activity. METHODS:The seven cDNAs of MDR1 from five animals were cloned, and their transformants stably expressing the series of MDR1 in LLC-PK1 were established. Transport studies of clarithromycin, daunorubicin, digoxin, erythromycin, etoposide, paclitaxel, propranolol, quinidine, ritonavir, saquinavir, verapamil, and vinblastine were performed by using these cells, and efflux activity was compared among the species. RESULTS:Except for propranolol, all compounds showed efflux activity in all transformants, and were judged to be substrates of P-gp. There were slight interspecies and interisoforms differences in the substrate recognition. However, the efflux ratio among the series of the MDR1 stably expressing cells showed good correlation as represented between human and monkey MDR1, and poor correlation as represented between human MDR1 and mouse mdr1a, and human and canine MDR1. CONCLUSIONS:Results in the present study indicate that all MDR1 stably expressing cells have efflux activity for various P-gp substrates, and that interspecies differences and similarities of the P-gp substrate efflux activity may exist.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Takeuchi T,Yoshitomi S,Higuchi T,Ikemoto K,Niwa S,Ebihara T,Katoh M,Yokoi T,Asahi Sdoi
10.1007/s11095-006-0285-7subject
Has Abstractpub_date
2006-07-01 00:00:00pages
1460-72issue
7eissn
0724-8741issn
1573-904Xjournal_volume
23pub_type
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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abstract::The pharmacokinetics of trilostane and one of its metabolites ketotrilostane are described and characterized in the rat following the separate intravenous administration of trilostane and ketotrilostane. It was noted during these studies that the parent compound and its metabolite undergo metabolic interconversion-tri...
journal_title:Pharmaceutical research
pub_type: 杂志文章
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
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journal_title:Pharmaceutical research
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abstract:PURPOSE:To develop an isolated perfused rat liver (IPRL) model with low baseline levels of tumor necrosis factor (TNF)-alpha in the outlet perfusate to study the effects of immunostimulants and immunosuppressants on the release of TNF-alpha from this organ. METHODS:Isolated rat livers were perfused with a buffer conta...
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
pub_type: 临床试验,杂志文章
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更新日期:2006-09-01 00:00:00
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更新日期:2016-10-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018977021183
更新日期:1992-02-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:2012-12-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:2013-10-01 00:00:00
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:1996-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:2010-09-01 00:00:00