Adefovir dipivoxil, a marketed drug for the treatment of hepatitis B, is dosed at submaximally efficacious doses because of renal toxicity. In an effort to improve the therapeutic index of adefovir, 1-aryl-1,3-propanyl prodrugs were synthesized with the rationale that this selectively liver-activated prodrug class would enhance liver levels of the active metabolite adefovir diphosphate (ADV-DP) and/or decrease kidney exposure. The lead prodrug (14, MB06866, pradefovir), identified from a variety of in vitro and in vivo assays, exhibited good oral bioavailability (F = 42%, mesylate salt, rat) and rate of prodrug conversion to ADV-DP. Tissue distribution studies in the rat using radiolabeled materials showed that cyclic 1-aryl-1,3-propanyl prodrugs enhance the delivery of adefovir and its metabolites to the liver, with pradefovir exhibiting a 12-fold improvement in the liver/kidney ratio over adefovir dipivoxil.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm7012216 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Hemophagocytic Lymphohistiocytosis Associated With Epstein-Barr Virus Infection in an Immunocompetent Adult.
Cureus
December 2024
Department of Internal Medicine, Unidade Local de Saúde Entre Douro e Vouga, Santa Maria da Feira, PRT.
Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal entity characterized by an unregulated activation of the immune system. In the adult population, it is most commonly secondary to infectious, autoimmune, or neoplastic diseases. We present a case of a 23-year-old female diagnosed with infectious mononucleosis and hospitalized due to a persistent three-week fever and malaise with a new onset of jaundice and findings compatible with acute hepatitis and hepatosplenomegaly.
View Article and Find Full Text PDFKnowledge, attitudes, practices, and vaccination coverage of medical students toward hepatitis B virus in North Sudan, 2023.
PeerJ
January 2025
Department of Internal Medicine, Faculty of Medicine and Health Science, University of Dongola, Dongola, Northern State, Sudan.
Background: Hepatitis B virus (HBV) is a global health issue, particularly among healthcare personnel, including students because of its occupational exposure pattern. Healthcare Workers and medical students are recommended to have better knowledge, attitudes and good practices and vaccination toward infection control in general and HBV in particular. This study aimed to assess the knowledge, attitudes, and practices of medical students from North Sudan regarding HBV and its vaccination coverage.
View Article and Find Full Text PDFCharacterization of Incident Hepatitis C Virus Infection among People Living with HIV in a HIV Clinic in Korea.
Infect Chemother
December 2024
Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Medical Center, Seoul, Korea.
Background: Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) can cause more rapid progression to cirrhosis than HCV-monoinfection. In this study, incident HCV case (IHCV)s were investigated in a HIV clinic in Korea.
Materials And Methods: A retrospective HIV cohort was constructed who visited National Medical Center in Korea from 2013 to 2022 and performed ≥ 1 anti-HCV antibody tests (anti-HCV) during the study period.
Multi-omics reveals the mechanism of Trimethylamine N-oxide derived from gut microbiota inducing liver fatty of dairy cows.
BMC Genomics
January 2025
College of Animal Science and Technology, Ningxia University, Yinchuan, 750021, China.
Background: Trimethylamine N-oxide (TMAO) is a metabolite produced by gut microbiota, and its potential impact on lipid metabolism in mammals has garnered widespread attention in the scientific community. Bovine fatty liver disease, a metabolic disorder that severely affects the health and productivity of dairy cows, poses a significant economic burden on the global dairy industry. However, the specific role and pathogenesis of TMAO in bovine fatty liver disease remain unclear, limiting our understanding and treatment of the condition.
View Article and Find Full Text PDFCobalt chloride-mimicked hepatocyte cell hypoxia induces TREX1 leading to Hepatitis B virus restriction.
J Infect Dis
January 2025
Institut Pasteur, Université de Paris Cité, Virus and Cellular Stress Unit, Department of Virology, Paris, France.
Background: Restriction factors are host cell proteins that play a role in limiting virus replication. They form part of the intrinsic immune system and function as a first line of defense against viral infections. Hepatitis B virus (HBV) does not escape this rule and TREX1, a host restriction enzyme acts as an antiviral factor, leading to the inhibition of the virus.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!