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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 4 h, 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 4 h, 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 released in liver homogenate, respectively. In vitro results showed that these bile acid conjugates are potential prolonged release prodrugs with binding affinity for ASBT.