Unknown

Dataset Information

0

Synthesis and Evaluation of Bile Acid-Ribavirin Conjugates as Prodrugs to Target the Liver.


ABSTRACT: Ribavirin is used to treat hepatitis C but causes serious hemolytic anemia. The objective of the study was to develop a ribavirin prodrug to achieve liver-specific drug delivery and to reduce its off-target effect in red blood cells (RBCs). The approach aimed to target the human sodium taurocholate cotransporting polypeptide (NTCP), which is a bile acid transporter predominately expressed in the liver. Six prodrugs with ribavirin conjugation at C-3 or C-24 of the bile acids were synthesized. In vitro uptake studies indicated that all six prodrugs were NTCP substrates. Metabolic studies in vitro indicated that ribavirin-l-Val-glycochenodeoxycholic acid (GCDCA) was able to release ribavirin in the mouse liver S9 fraction. Additionally, in vitro studies showed that ribavirin in RBC was reduced by 16.7-fold from prodrug compared with parent drug incubation. Moreover, almost no prodrug was present in RBC. In vivo study in mice also showed that ribavirin-l-Val-GCDCA could provide almost the same ribavirin exposure in the liver as ribavirin administration, but with about 1.8-fold less exposure of ribavirin in RBC, plasma, and kidney. Overall, the study suggested that ribavirin-l-Val-GCDCA has the potential to achieve ribavirin-specific liver delivery.

SUBMITTER: Dong Z 

PROVIDER: S-EPMC4522399 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

Synthesis and Evaluation of Bile Acid-Ribavirin Conjugates as Prodrugs to Target the Liver.

Dong Zhongqi Z   Li Qing Q   Guo Dong D   Shu Yan Y   Polli James E JE  

Journal of pharmaceutical sciences 20150202 9


Ribavirin is used to treat hepatitis C but causes serious hemolytic anemia. The objective of the study was to develop a ribavirin prodrug to achieve liver-specific drug delivery and to reduce its off-target effect in red blood cells (RBCs). The approach aimed to target the human sodium taurocholate cotransporting polypeptide (NTCP), which is a bile acid transporter predominately expressed in the liver. Six prodrugs with ribavirin conjugation at C-3 or C-24 of the bile acids were synthesized. In  ...[more]

Similar Datasets

| S-EPMC6214026 | biostudies-literature
| S-EPMC6630699 | biostudies-literature
| S-EPMC10179906 | biostudies-literature
| S-EPMC10244448 | biostudies-literature
| S-EPMC2409274 | biostudies-literature
| S-EPMC4769951 | biostudies-literature
2024-10-09 | GSE279099 | GEO
| S-EPMC2997912 | biostudies-literature
| S-EPMC8472512 | biostudies-literature
| S-EPMC10452260 | biostudies-literature