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Pharmacokinetics of Jnj-73763989 And Jnj-56136379 (Bersacapavir) In Participants With Moderate Hepatic Impairment
This article is protected by copyright. All rights reserved.PMID:36786053 | DOI:10.1002/jcph.2214
Source: The Journal of Clinical Pharmacology - February 14, 2023 Category: Drugs & Pharmacology Authors: Thomas N Kakuda Atef Halabi Gernot Klein Madhu Sanga Carine Guinard-Azadian Monika Kowalik Katja Nedoschinsky Julius Nangosyah Emmanuel Njumbe Ediage Vera Hillewaert Peter Verboven Ivo Goris Jan Snoeys Martyn Palmer Michael Biermer Source Type: research

Pharmacokinetics, Safety, and Tolerability of the siRNA JNJ ‐73763989 in Healthy Chinese Adult Participants
AbstractJNJ-73763989, composed of the 2 short-interfering RNA triggers JNJ-73763976 and JNJ-73763924, targets all hepatitis B virus messenger RNAs, thereby reducing all viral proteins. In this phase 1, single-site, open-label, parallel-group, randomized study, participants were given 1 subcutaneous injection of JNJ-73763989 (100 or 200  mg) to investigate the pharmacokinetics, safety, and tolerability of JNJ-73763989 in healthy Chinese adult participants. Plasma and urine pharmacokinetic parameters were determined for each trigger up to 48 hours after dosing. Eighteen participants, 9 per dose group, were enrolled. The me...
Source: Clinical Pharmacology in Drug Development - November 23, 2022 Category: Drugs & Pharmacology Authors: Haiyan Li, Xiaoye Niu, Yu Zhang, Danning Zhang, Yanqing Zhang, Liqun Wang, Yongqing Miao, Yanxin Jiang, Jia Ji, Qiaoqiao Chen, Xiaoyun Wu, Emmanuel Njumbe Ediage, Thomas N. Kakuda, Michael Biermer Tags: Original Article Source Type: research

Vitexin attenuates autoimmune hepatitis in mouse induced by syngeneic liver cytosolic proteins via activation of AMPK/AKT/GSK-3 β/Nrf2 pathway
In conclusion, vitexin ameliorated hepatic injury in EAH mice through activation of the AMPK/AKT/GSK-3β pathway and upregulation of the Nrf2 gene.PMID:34953801 | DOI:10.1016/j.ejphar.2021.174720
Source: European Journal of Pharmacology - December 26, 2021 Category: Drugs & Pharmacology Authors: Lei Zhang Dazhi Chen Yulu Tu Tiantian Sang Tongtong Pan Hongwei Lin Chao Cai Xiaozhi Jin Faling Wu Lanman Xu Yongping Chen Source Type: research

Anti-inflammatory and anti-fibrotic effects of modafinil in nonalcoholic liver disease
Biomed Pharmacother. 2021 Dec;144:112372. doi: 10.1016/j.biopha.2021.112372. Epub 2021 Oct 28.ABSTRACTSmall- and intermediate-conductance Ca2+-activated K+ channels, KCa2.3 and KCa3.1, are involved in cellular signaling processes associated with inflammation and fibrosis. KCa2.3 and KCa3.1 are upregulated by proinflammatory cytokines and profibrotic growth factors. Cyclic AMP, which downregulates KCa2.3 and KCa3.1, is elevated by modafinil in cells; accordingly, we investigated whether modafinil exerts anti-inflammatory and anti-fibrotic responses via KCa2.3- and KCa3.1-mediated pathways in high-fat diet (HFD)- or thioacet...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - November 19, 2021 Category: Drugs & Pharmacology Authors: Shinkyu Choi Ji Aee Kim Haiyan Li Seong-Eun Jo Huisu Lee Tae Hun Kim Minje Kim Seong-Jin Kim Suk Hyo Suh Source Type: research

TLR4 promotes liver inflammation by activating the JNK pathway.
CONCLUSIONS: APAP-treated TLR4-/- mice showed milder liver injury compared to WT mice. It was confirmed that TLR4 could activate the JNK signaling pathway to induce the secretion of inflammatory factors and the infiltration of macrophages to promote APAP-induced liver injury. This finding might provide a new prevention and treatment idea for clinical drug-induced hepatitis. PMID: 31539158 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - September 22, 2019 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

siRNA drug development against hepatitis B virus infection
Volume 18, Issue 6, June 2018, Page 609-617 .
Source: Expert Opinion on Biological Therapy - May 8, 2018 Category: Drugs & Pharmacology Authors: Robert Flisiak Jerzy Jaroszewicz Mariusz Łucejko Source Type: research

Safety, Tolerability, and Pharmacokinetics of ARC ‐520 Injection, an RNA Interference‐Based Therapeutic for the Treatment of Chronic Hepatitis B Virus Infection, in Healthy Volunteers
Abstract ARC‐520 Injection, an RNA interference drug for the treatment of hepatitis B that targets cccDNA‐derived viral mRNA transcripts with high specificity, effectively reduces the production of viral proteins and HBV DNA. In this phase 1 randomized, double‐blind, placebo‐controlled study, 54 healthy volunteers (half male, half female) received a single, intravenous dose of 0.01–4.0 mg/kg ARC‐520 Injection (n = 36) or placebo (n = 18). Assessments included safety, tolerability, pharmacokinetics, and pharmacodynamics (cytokines and complement). Pharmacokinetics of the siRNA and peptide excipient components co...
Source: Clinical Pharmacology in Drug Development - December 11, 2016 Category: Drugs & Pharmacology Authors: Thomas Schluep, Jason Lickliter, James Hamilton, David L. Lewis, Ching ‐Lung Lai, Johnson YN Lau, Stephen A. Locarnini, Robert G. Gish, Bruce D. Given Tags: Original Article Source Type: research

Hepatic Stellate Cells in Liver Fibrosis and siRNA-Based Therapy.
Abstract Hepatic fibrosis is a reversible wound-healing response to either acute or chronic liver injury caused by hepatitis B or C, alcohol, and toxic agents. Hepatic fibrosis is characterized by excessive accumulation and reduced degradation of extracellular matrix (ECM). Excessive accumulation of ECM alters the hepatic architecture leading to liver fibrosis and cirrhosis. Cirrhosis results in failure of common functions of the liver. Hepatic stellate cells (HSC) play a major role in the development of liver fibrosis as HSC are the main source of the excessive production of ECM in an injured liver. RNA interfere...
Source: Pharmacological Reviews - August 17, 2016 Category: Drugs & Pharmacology Authors: Omar R, Yang J, Liu H, Davies NM, Gong Y Tags: Rev Physiol Biochem Pharmacol Source Type: research

RNA Interference as a Therapeutic Strategy for the Treatment of Liver Diseases.
Abstract RNA interference has emerged as an innovative technology for gene silencing that degrades mRNAs complementary to the antisense strands of double-stranded, short interfering RNAs (siRNAs). Its therapeutic application has important advantages over small-molecule drugs since offers the possibility of targeting virtually all genes and allows selective silencing of one or several genes. So far, a relative small proportion of cellular proteins can bind and respond to chemical drugs. Based on that, RNA interference-mediated gene silencing is widely considered as a crucial breakthrough in molecular biology with a...
Source: Current Pharmaceutical Design - October 23, 2015 Category: Drugs & Pharmacology Authors: Gonzalez-Rodriguez A, Valverde AM Tags: Curr Pharm Des Source Type: research

New and Emerging Agents for the Treatment of Hemophilia: Focus on Extended Half-Life Recombinant Clotting Proteins
Abstract Hemophilia A and B are X-linked disorders caused by deficient or defective clotting factor VIII (FVIII) or IX factor (FIX) proteins, and characterized by spontaneous or traumatic bleeding into joints and muscles. Previous use of plasma and plasma-derived clotting factors that lacked appropriate viral inactivation steps in manufacturing led to significant morbidity associated with transfusion-transmitted HIV and hepatitis C virus (HCV). The development of recombinant proteins revolutionized their treatment, and, with no new HIV or HCV infection via clotting proteins for nearly 30 years, greatly improved t...
Source: Drugs - August 27, 2015 Category: Drugs & Pharmacology Source Type: research

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