Abstract：
PURPOSE:To synthesize a trifluorinated bile acid that can be used for (19)F magnetic resonance imaging (MRI) of bile acid enterohepatic circulation, characterize its in vitro transporter affinity, stability, and (19)F-MRI signal, and assess its ability to concentrate in the gallbladder of C57BL/6 mice. METHODS:Target compound CA-lys-TFA was synthesized and tested for affinity toward the apical sodium dependent bile acid transporter (hASBT) and the Na+/taurocholate cotransporting polypeptide (hNTCP). In a pilot study, fasted mice were gavaged with vehicle control, 150 mg/kg or 300 mg/kg CA-lys-TFA. CA-lys-TFA in gallbladder, liver and plasma at t = 5 h was quantified. Additionally, a 24-h time course (24 mice across eight time points) was studied using 50 mg/kg CA-lys-TFA. RESULTS:CA-lys-TFA was a potent substrate of hASBT (Kt = 39.4 μM, normalized Vmax = 0.853) and hNTCP (Kt = 8.99 μM, normalized Vmax = 0.281). (19)F MRI phantom imaging showed linear signal-concentration dependence. In vivo studies showed that rapid accumulation of CA-lys-TFA in the gallbladder was maximal within 4-7 h. CONCLUSIONS:These findings suggest that CA-lys-TFA, a fluorinated non-radioactive bile acid analogue, has potential for use in MRI to measure in vivo bile acid transport and diagnose bile acid malabsorption and other conditions associated with impaired bile acid transport.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Vivian D,Cheng K,Khurana S,Xu S,Whiterock V,Witter D,Lentz KA,Santone KS,Raufman JP,Polli JEdoi
10.1007/s11095-012-0963-6subject
Has Abstractpub_date
2013-05-01 00:00:00pages
1240-51issue
5eissn
0724-8741issn
1573-904Xjournal_volume
30pub_type
杂志文章abstract：:Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains that affects ~1% of the white ethnic population. In the last decades, a rise in prevalence of CD has been observed that cannot be fully explained by improved diagnostics. Genetic predisposition greatly influenc...
journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：2013-03-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
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更新日期：2018-04-26 00:00:00
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journal_title：Pharmaceutical research
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doi：10.1007/s11095-014-1398-z
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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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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-2085-z
更新日期：2017-03-01 00:00:00
abstract：PURPOSE:Interferon beta is commonly used as therapeutic in the first line of therapy for multiple sclerosis. However, depending on the product, it induces an antibody response in up to 60% of patients. This study evaluated the impact of therapy related factors like dose, route of administration and administration frequ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：2013-06-01 00:00:00
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journal_title：Pharmaceutical research
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doi：10.1007/s11095-014-1349-8
更新日期：2014-09-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016401405119
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journal_title：Pharmaceutical research
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更新日期：1985-11-01 00:00:00
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pub_type： 杂志文章
doi：10.1007/s11095-005-7677-y
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journal_title：Pharmaceutical research
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doi：10.1007/s11095-010-0277-5
更新日期：2010-12-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：2012-09-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：2006-02-01 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：2006-05-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：1992-11-01 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：2019-02-22 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0875-5
更新日期：2013-02-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
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更新日期：2008-12-01 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：2008-08-01 00:00:00
abstract：PURPOSE:The purpose of this work was to investigate the mechanisms of cocrystal formation during cogrinding and storage of solid reactants, and to establish the effects of water by cogrinding with hydrated form of reactants and varying RH conditions during storage. METHODS:The hydrogen bonded 1:1 carbamazepine-sacchar...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9110-6
更新日期：2006-10-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2392-7
更新日期：2018-03-29 00:00:00
