Evidence map›Paper›PMID 25645375›Full record

ArticleJournal of pharmaceutical sciences2015

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

Zhongqi Dong, Qing Li, Dong Guo, Yan Shu, James E Polli

Open access · greenAbstract read
In one paragraph

Article in Journal of pharmaceutical sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.3field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Article
  3. Transporter-Mediated Drug Delivery.Molecules (Basel, Switzerland) · 2023
    Review
  4. Review
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Zhongqi DongDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland, 21201.
Qing LiDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland, 21201.
Dong GuoDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland, 21201.
Yan ShuDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland, 21201.
James E PolliDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland, 21201.
University of Maryland, Baltimore · US

Funding

University of Maryland Center of Excellence in Regulatory Science and InnovationU01FD005946 · FDA · UNIV OF MARYLAND, COLLEGE PARK · PI BENTLEY, WILLIAM E., POLLI, JAMES E · 2016 to 2025
$21.5M
University of Maryland Center of Excellence in Regulatory Science and InnovationU01FD004320 · FDA · UNIV OF MARYLAND, COLLEGE PARK · PI BENTLEY, WILLIAM E., POLLI, JAMES E · 2011 to 2016
$3.8M
Creating a toolkit to measure in vivo bile acid transportR21DK093406 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI POLLI, JAMES E, RAUFMAN, JEAN-PIERRE · 2012 to 2013
$404k
FDA HHS U01 FD004320FDA HHS U01FD004320-01FDA HHS U01 FD005946NIDDK NIH HHS DK093406NIDDK NIH HHS R21 DK093406
6 · The paper itself

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.

Indexed as

ProdrugsAnimalsAntiviral AgentsBile Acids and SaltsCell LineDrug Delivery SystemsDrug StabilityErythrocytesHumansIn Vitro TechniquesKidneyLiverMiceOrganic Anion Transporters, Sodium-DependentRibavirinSymportersAntiviral AgentsBile Acids and SaltsOrganic Anion Transporters, Sodium-DependentProdrugsRibavirinsodium-bile acid cotransporterSymportersbile acid transportershepatocytesmetabolismNTCPprodrugsribavirinsite-specific delivery

Identifiers

PMID25645375
PMCPMC4522399
OpenAlexW2076726517

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.