Synthesis and in vitro evaluation of potential sustained release prodrugs via targeting ASBT.
Synthesis and in vitro evaluation of potential sustained release prodrugs via targeting ASBT.
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DOI：
10.1016/j.ijpharm.2010.06.039
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发表时间：
2010-08-30
影响因子：
5.8
通讯作者：
Polli, James E.
中科院分区：
文献类型：
--
作者：
Zheng, Xiaowan;Polli, James E.
The objective was to synthesize prodrugs of niacin and ketoprofen that target the human apical sodium-dependent bile acid transporter (ASBT) and potentially allow for prolonged drug release. Each drug was conjugated to the naturally occurring bile acid chenodeoxycholic acid (CDCA) using lysine as a linker. Their inhibitory binding and transport properties were evaluated in stably transfected ASBT-MDCK monolayers, and the kinetic parameters Ki, Kt, normJmax, and Pp were characterized. Enzymatic stability of the conjugates was evaluated in Caco-2 and liver homogenate. Both conjugates were potent inhibitors of ASBT. For the niacin prodrug, substrate kinetic parameter Kt was 8.22 μM and normJmax was 0.0917. In four hours, 69.4% and 26.9% of niacin was released from 1 μM and 5 μM of the conjugate in Caco-2 homogenate, respectively. For the ketoprofen prodrug, Kt was 50.8 μM and normJmax was 1.58. In four hours, 5.94% and 3.73% of ketoprofen was released from 1 μM and 5 μM of the conjugate in Caco-2 homogenate, and 24.5% and 12.2% of ketoprofen was release in liver homogenate, respectively. In vitro results showed that these bile acid conjugates are potential prolonged release prodrugs with binding affinity for ASBT.
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DOI：
10.1124/jpet.107.135863
发表时间：
2008-07-01
影响因子：
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作者：
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Offermanns, S
影响因子：
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作者：
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