Abstract:
:To investigate the transport function of the blood-brain barrier (BBB), we employed an in vitro model of the BBB, consisting of a co-culture of porcine brain capillary endothelial cells (BCECs) with rat astrocytes. Porcine BCECs were cultured on a filter insert with rat astrocytes on the underlying plastic well. Rat astrocytes induced characteristic BBB properties of porcine BCECs, such as gamma-glutamyl-transpeptidase activity and intercellular adhesion of porcine BCECs. Next, the transport properties of P-glycoprotein (P-gp) substrate and several anionic compounds across the co-cultured porcine BCECs were characterized. Expression of P-gp was detected by immunocytochemistry, and efflux-directed transport of the P-gp substrate [(3)H]daunomycin was observed. Luminal-to-abluminal transport of the monocarboxylic acid transporter 1 (MCT1) substrate [(14)C]benzoic acid was saturable, and the K(m) value (3.05 mM) was similar to that for brain uptake observed in vivo. Abluminal-to-luminal transport of [(14)C]benzoic acid was also saturable, indicating that the monocarboxylic acid transporter of the BBB contributes to the efflux from the brain as well as to blood-to-brain influx. Abluminal-to-luminal transport of organic anions, [(3)H]dehydroepiandrosterone sulfate, [(3)H]estrone sulfate and [(3)H]estradiol 17beta-D-glucuronide was significantly higher than the corresponding luminal-to-abluminal transport. These results demonstrate the presence of multiple efflux transport pathways in this in vitro model.
journal_name
Drug Metab Pharmacokinetjournal_title
Drug metabolism and pharmacokineticsauthors
Kido Y,Tamai I,Nakanishi T,Kagami T,Hirosawa I,Sai Y,Tsuji Adoi
10.2133/dmpk.17.34subject
Has Abstractpub_date
2002-01-01 00:00:00pages
34-41issue
1eissn
1347-4367issn
1880-0920pii
JST.JSTAGE/dmpk/17.34journal_volume
17pub_type
杂志文章abstract::Maleic acid (MA) was purposefully adulterated in an array of starch-based foods in Taiwan, inciting a food safety incident. Due to limited data on the pharmacokinetics and bioavailability of ingested MA, we studied pharmacokinetic (PK) parameters in serum and urine of Sprague Dawley rats. Three groups of male and fema...
journal_title:Drug metabolism and pharmacokinetics
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journal_title:Drug metabolism and pharmacokinetics
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journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
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更新日期:2011-06-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Drug metabolism and pharmacokinetics
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journal_title:Drug metabolism and pharmacokinetics
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更新日期:2005-04-01 00:00:00
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更新日期:2011-01-01 00:00:00
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journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.24.333
更新日期:2009-01-01 00:00:00
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journal_title:Drug metabolism and pharmacokinetics
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doi:10.2133/dmpk.21.375
更新日期:2006-10-01 00:00:00
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journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章,评审
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更新日期:2003-01-01 00:00:00
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更新日期:2002-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.dmpk.2018.04.002
更新日期:2018-08-01 00:00:00
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journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.25.149
更新日期:2010-01-01 00:00:00
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pub_type: 杂志文章,随机对照试验
doi:10.1016/j.dmpk.2017.12.001
更新日期:2018-06-01 00:00:00
abstract:UNLABELLED:Better prediction of drug disposition prior to the clinical trial is critical for the efficient development of new drugs. The purpose of this study is to develop a novel multiple assessment methodology of hepatocellular drug disposition from drug uptake to efflux including biliary and basolateral excretion, ...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1016/j.dmpk.2015.12.001
更新日期:2016-04-01 00:00:00
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journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1016/j.dmpk.2019.10.002
更新日期:2020-02-01 00:00:00
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journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1016/j.dmpk.2020.03.003
更新日期:2020-06-01 00:00:00
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journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1016/j.dmpk.2015.04.005
更新日期:2015-08-01 00:00:00
abstract::Tacrolimus is a widely used immunosuppressant after organ transplantation. The narrow therapeutic window and individual variability in tacrolimus pharmacokinetics make management of this agent a great challenge. This study was undertaken to determine the association of clinical markers, cytochrome P450, family 3, subf...
journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.2133/dmpk.dmpk-13-rg-095
更新日期:2014-01-01 00:00:00