Repurposed drug battles ‘brain-eating’ amoeba
In the summer of 2021, a 54-year-old man was brought to a hospital in Northern California after an unexplained seizure. When an MRI revealed a mysterious mass in the left side of his brain, he was transferred to the University of California, San Francisco (UCSF), Medical Center. A brain biopsy and other tests revealed not a tumor, but an incredibly rare infection of the central nervous system caused by the amoeba
Balamuthia mandrillaris
. One of several “brain-eating” amoebae that occasionally spark headlines, the pathogen kills more than 90% of people who contract it.
But despite initial setbacks, the ...
Source: Science of Aging Knowledge Environment - February 3, 2023 Category: Geriatrics Source Type: research
The cardinal trial of bardoxolone methyl in alport syndrome: when marketing interests prevail over patients clinical needs
Context. Alport syndrome (AS) is a hereditary chronic kidney disease (CKD) with X-linked, autosomal and digenic patterns of transmission. Sieving dysfunction of the glomerular basement membrane caused by congenitally defective type IV collagen results in persistent proteinuria, hematuria and progressive renal dysfunction. There are no disease-specific medications and treatment is based on conservative interventions in particular with renin-angiotensin-aldosterone system inhibitors.
Subject of Review. Evidence that AS is accompanied by glomerular and tubular inflammatory changes and that bardoxolone methyl exerts anti-infl...
Source: Nephron - February 2, 2023 Category: Urology & Nephrology Source Type: research
Regulatory Utility of Mechanistic Modeling to Support Alternative Bioequivalence Approaches: A Workshop Overview
AbstractOn September 30 and October 1, 2021, the U.S. Food and Drug Administration and the Center for Research on Complex Generics co-sponsored a live virtual workshop titled “Regulatory Utility of Mechanistic Modeling to Support Alternative Bioequivalence Approaches.” The overall aims of the workshop included: (i) engaging the generic drug industry and other involved stakeholders regarding how mechanistic modeling and simulation can support their product development and regulatory submissions; (ii) sharing the current state of mechanistic modeling for bioequivalence assessment through case studies; (iii) establishing ...
Source: CPT: Pharmacometrics and Systems Pharmacology - January 12, 2023 Category: Drugs & Pharmacology Authors: Andrew Babiskin,
Fang Wu,
Youssef Mousa,
Ming ‐Liang Tan,
Eleftheria Tsakalozou,
Ross L. Walenga,
Miyoung Yoon,
Sam G. Raney,
James E. Polli,
Anna Schwendeman,
Vishalakshi Krishnan,
Lanyan Fang,
Liang Zhao Tags: MINI REVIEW Source Type: research
Modeling Approaches to Reimagine Stability (MARS) for Enabling Earlier Access to Critical Drugs for Patients with Unmet Medical Needs
In this study, a data mining exercise has been conducted with regulatory submissions of Investigational New Drug (IND) Applications, NDAs, and Abbreviated New Drug Applications (ANDAs) containing MARS data. The case studies presented herein demonstrate how MARS data has been applied to regulatory scenarios involving prediction of retest and/or shelf-life, bridging major development changes, and confirming that no degradation has been observed or predicted. Using the assumption of a linear time trend for those cases that do not display sufficient degradation to conduct MARS for projection of an expiration date, an analysis ...
Source: AAPS PharmSciTech - January 11, 2023 Category: Drugs & Pharmacology Authors: M Scott Furness Hong Cai Sithamalli Chandramouli Mariappan Chelliah Xiao Hong Chen Debasis Ghosh Shaobo Liu Sherita McLamore Ramnarayan Randad Meiyu Shen Source Type: research
Modeling Approaches to Reimagine Stability (MARS) for Enabling Earlier Access to Critical Drugs for Patients with Unmet Medical Needs
In this study, a data mining exercise has been conducted with regulatory submissions of Investigational New Drug (IND) Applications, NDAs, and Abbreviated New Drug Applications (ANDAs) containing MARS data. The case studies presented herein demonstrate how MARS data has been applied to regulatory scenarios involving prediction of retest and/or shelf-life, bridging major development changes, and confirming that no degradation has been observed or predicted. Using the assumption of a linear time trend for those cases that do not display sufficient degradation to conduct MARS for projection of an expiration date, an analysis ...
Source: AAPS PharmSciTech - January 11, 2023 Category: Drugs & Pharmacology Authors: M Scott Furness Hong Cai Sithamalli Chandramouli Mariappan Chelliah Xiao Hong Chen Debasis Ghosh Shaobo Liu Sherita McLamore Ramnarayan Randad Meiyu Shen Source Type: research
ASK120067 potently suppresses B-cell or T-cell malignancies in vitro and in vivo by inhibiting BTK and ITK
Hyperactivation of Bruton’s tyrosine kinase (BTK) or interleukin-2-inducible T cell kinase (ITK) has been attributed to the pathogenesis of B-cell lymphoma or T-cell leukemia, respectively, which suggests that Bruton’s tyrosine kinase and interleukin-2-inducible T cell kinase are critical targets for the treatment of hematological malignancies. We identified a novel third-generation epidermal growth factor receptor (EGFR) inhibitor, ASK120067 (limertinib) in our previous research, which has been applied as a new drug application against non-small cell lung cancer in China. In this work, we found that ASK120067 displaye...
Source: Frontiers in Pharmacology - December 15, 2022 Category: Drugs & Pharmacology Source Type: research
Overview of Clinical Pharmacology Packages of New Drug Applications Approved for the Treatment of Rare Diseases
J Clin Pharmacol. 2022 Dec;62 Suppl 2:S72-S78. doi: 10.1002/jcph.2167.NO ABSTRACTPMID:36461747 | DOI:10.1002/jcph.2167 (Source: The Journal of Clinical Pharmacology)
Source: The Journal of Clinical Pharmacology - December 3, 2022 Category: Drugs & Pharmacology Authors: Hisham Qosa Hazem E Hassan Islam R Younis Source Type: research
Overview of Clinical Pharmacology Packages of New Drug Applications Approved for the Treatment of Rare Diseases
J Clin Pharmacol. 2022 Dec;62 Suppl 2:S72-S78. doi: 10.1002/jcph.2167.NO ABSTRACTPMID:36461747 | DOI:10.1002/jcph.2167 (Source: The Journal of Clinical Pharmacology)
Source: The Journal of Clinical Pharmacology - December 3, 2022 Category: Drugs & Pharmacology Authors: Hisham Qosa Hazem E Hassan Islam R Younis Source Type: research
Overview of Clinical Pharmacology Packages of New Drug Applications Approved for the Treatment of Rare Diseases
J Clin Pharmacol. 2022 Dec;62 Suppl 2:S72-S78. doi: 10.1002/jcph.2167.NO ABSTRACTPMID:36461747 | DOI:10.1002/jcph.2167 (Source: The Journal of Clinical Pharmacology)
Source: The Journal of Clinical Pharmacology - December 3, 2022 Category: Drugs & Pharmacology Authors: Hisham Qosa Hazem E Hassan Islam R Younis Source Type: research
Overview of Clinical Pharmacology Packages of New Drug Applications Approved for the Treatment of Rare Diseases
J Clin Pharmacol. 2022 Dec;62 Suppl 2:S72-S78. doi: 10.1002/jcph.2167.NO ABSTRACTPMID:36461747 | DOI:10.1002/jcph.2167 (Source: The Journal of Clinical Pharmacology)
Source: The Journal of Clinical Pharmacology - December 3, 2022 Category: Drugs & Pharmacology Authors: Hisham Qosa Hazem E Hassan Islam R Younis Source Type: research
XiaoEr LianHuaQinqGan alleviates viral pneumonia in mice infected by influenza A and respiratory syncytial viruses
CONCLUSION: XELH efficacy partially depends on integrated immunoregulatory effects. XELH is a promising therapeutic option against childhood respiratory viral infections.PMID:36444944 | DOI:10.1080/13880209.2022.2147961 (Source: Pharmaceutical Biology)
Source: Pharmaceutical Biology - November 29, 2022 Category: Drugs & Pharmacology Authors: Wenyan Li Tongtong Li Chi Zhao Tao Song Yao Mi Zhang Chuangfeng Yunlong Hou Zhenhua Jia Source Type: research
Animal use and opportunities for reduction in carcinogenicity studies supporting approved new drug applications in the U.S., 2015-2019
Regul Toxicol Pharmacol. 2022 Nov 12:105289. doi: 10.1016/j.yrtph.2022.105289. Online ahead of print.ABSTRACTA minimum of 65,341 rats and mice were used in 109 carcinogenicity studies conducted for new drug applications approved by the U.S. Food and Drug Administration from 2015 through 2019. By analyzing how these animals were used, we compared the potential for reducing animal use of implementing existing international guidelines and recommendations. The greatest reduction, 18.7%, would result from evaluating exposure by microsampling blood in main studies to replace toxicokinetics satellites, which used three-fold more ...
Source: Regulatory Toxicology and Pharmacology : RTP - November 15, 2022 Category: Toxicology Authors: Joseph Manuppello Eryn Slankster-Schmierer Elizabeth Baker Kristie Sullivan Source Type: research
Animal use and opportunities for reduction in carcinogenicity studies supporting approved new drug applications in the U.S., 2015-2019
Regul Toxicol Pharmacol. 2022 Nov 12:105289. doi: 10.1016/j.yrtph.2022.105289. Online ahead of print.ABSTRACTA minimum of 65,341 rats and mice were used in 109 carcinogenicity studies conducted for new drug applications approved by the U.S. Food and Drug Administration from 2015 through 2019. By analyzing how these animals were used, we compared the potential for reducing animal use of implementing existing international guidelines and recommendations. The greatest reduction, 18.7%, would result from evaluating exposure by microsampling blood in main studies to replace toxicokinetics satellites, which used three-fold more ...
Source: Regulatory Toxicology and Pharmacology : RTP - November 15, 2022 Category: Toxicology Authors: Joseph Manuppello Eryn Slankster-Schmierer Elizabeth Baker Kristie Sullivan Source Type: research
A Survey of Population Pharmacokinetic Reports Submitted to the USFDA: An Analysis of Common Issues in NDA and BLA from 2012 to 2021
ConclusionThe findings from this study may help the applicant understand the FDA ’s thinking on the PopPK analysis. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - October 31, 2022 Category: Drugs & Pharmacology Source Type: research
