Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

2014 ◽  
Vol 279 (3) ◽  
pp. 467-476 ◽  
Author(s):  
Nanjun Liu ◽  
Elizabeth A. Tengstrand ◽  
Lisa Chourb ◽  
Frank Y. Hsieh
Keyword(s):  
Drug Development ◽  
Safety Assessment ◽  
Drug Induced ◽  
Clinical Biomarker

scholarly journals Qualification of translational safety biomarkers

2021 ◽  
pp. 153537022110021
Author(s):  
John-Michael Sauer ◽  
Amy C Porter
Keyword(s):  
Skeletal Muscle ◽  
Drug Development ◽  
Vascular Injury ◽  
Validation Studies ◽  
Safety Assessment ◽  
Regulatory Agencies ◽  
Development Studies ◽  
Clinical Validation ◽  
Development Tools ◽  
Important Drug

Safety biomarkers are important drug development tools, both preclinically and clinically. It is a straightforward process to correlate the performance of nonclinical safety biomarkers with histopathology, and ideally, the biomarker is useful in all species commonly used in safety assessment. In clinical validation studies, where histopathology is not feasible, safety biomarkers are compared to the response of standard biomarkers and/or to clinical adjudication. Worldwide, regulatory agencies have put in place processes to qualify biomarkers to provide confidence in the manner of use and interpretation of biomarker data in drug development studies. This paper describes currently qualified safety biomarkers which can be utilized to monitor for nephrotoxicity and cardiotoxicity and ongoing projects to qualify safety biomarkers for liver, skeletal muscle, and vascular injury. In many cases, the development and use of these critical drug development tools is dependent upon partnerships and the precompetitive sharing of data to support qualification efforts.

Aggregate Safety Assessment Planning for the Drug Development Life-Cycle

2021 ◽  
Author(s):  
Barbara A. Hendrickson ◽  
William Wang ◽  
Greg Ball ◽  
Dimitri Bennett ◽  
Amit Bhattacharyya ◽  
...  
Keyword(s):  
Life Cycle ◽  
Drug Development ◽  
Safety Assessment ◽  
Development Life Cycle

Drug-induced QTc interval prolongation: A proposal towards an efficient and safe anticancer drug development

2008 ◽  
Vol 44 (4) ◽  
pp. 494-500 ◽  
Author(s):  
Giuseppe Curigliano ◽  
Gianluca Spitaleri ◽  
Howard J. Fingert ◽  
Filippo de Braud ◽  
Cristiana Sessa ◽  
...  
Keyword(s):  
Drug Development ◽  
Anticancer Drug ◽  
Qtc Interval ◽  
Interval Prolongation ◽  
Drug Induced ◽  
Qtc Interval Prolongation ◽  
Anticancer Drug Development

A review of drug-induced Leydig cell hyperplasia and neoplasia in the rat and some comparisons with man

1995 ◽  
Vol 14 (7) ◽  
pp. 562-572 ◽  
Author(s):  
DE Prentice ◽  
AW Meikle
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Safety Assessment ◽  
Hormonal Status ◽  
Control Mechanisms ◽  
Hormone Production ◽  
Drug Induced ◽  
Cell Hyperplasia ◽  
Etiological Factors ◽  
Func Tion

This paper describes control of normal Leydig cell func tion and testosterone production. The macroscopic and histopathological appearances of spontaneous Leydig cell hyperplasias and tumors (LCT) in the rat are reviewed together with their incidence and hormonal status. Drugs which induce LCTs in chronic studies are discussed and include busereline, carbamazepine, cimetidine, finas teride, flutamide, gemfibrozil, histrelin, hydralazine, indomethacin, isradipine, lactitol, leuprolide, metronida zole, mesulergine, nafarelin, norprolac and vidarabine. The known mechanisms of LCT induction in the rat are reviewed together with other possible etiological factors. The incidence, clinical picture and etiological factors of LCTs in man are also surveyed. Hormone production in Leydig cells and LCTs in rats and man are compared. Differences between the two species are considered, par ticularly with regard to Leydig cell control mechanisms. The paper concludes that drug-induced LCTs in rats are most probably not predictive for man and their occurrence has little relevance in human safety assessment.

Drug-induced cardiac toxicity: emphasizing the role of electrocardiography in clinical research and drug development

2004 ◽  
Vol 37 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Ihor Gussak ◽  
Jeffrey Litwin ◽  
Robert Kleiman ◽  
Scott Grisanti ◽  
Joel Morganroth
Keyword(s):  
Drug Development ◽  
Clinical Research ◽  
Cardiac Toxicity ◽  
Drug Induced

Abstract 211: Automated and Non-invasive Estimation of QT Interval from Microscopy Images of Stem Cell-Derived Cardiomyocytes

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Mahnaz Maddah ◽  
Kevin Loewke
Keyword(s):  
Drug Development ◽  
Qt Interval ◽  
Cellular Response ◽  
Cardiovascular Health ◽  
New Drugs ◽  
Patient Specific ◽  
Current Standard ◽  
Drug Induced ◽  
Safety Testing ◽  
Non Invasive

A promising application of induced pluripotent stem cells (iPSCs) is the generation of patient-specific cardiomyocytes (CMs), which can be used for drug development and safety testing related to cardiovascular health. iPSC-derived CMs can be used for preclinical testing of new drugs that may cause drug-induced arrhythmia or long QT syndrome, as well as post-market safety testing of existing drugs. The measurement of QT interval for iPSC-derived CMs is commonly analyzed using electrophysiological potentials captured by a micro-electrode array (MEA). While such systems are the current standard for characterization, they can be expensive and low-throughput, require high cell plating density, and due to the direct contact between cells and electrodes, may cause undesirable cellular response. Here, we present a new method to non-invasively measure the QT-interval in iPSC-derived CMs using video microscopy and computer vision analysis. Our algorithms can reliably and automatically extract beating signal characteristics such as frequency, irregularity, and duration through image analysis of cardiomyocyte motion. Through a correlative study with MEA, we demonstrate that a non-invasive measurement of QT interval can be derived from the duration of visible cellular motion that occurs during contraction and relaxation. We also show that our system can accurately characterize the cellular response from the addition of compounds known to modulate beating frequency and irregularity. Our measurement technique is robust, automated, and requires no physical or chemical contact with the cells, making it ideal for cardiovascular drug development and cardiotoxicity testing.

scholarly journals Evaluation of the relevance of DILI predictive hypotheses in early drug development: review of in vitro methodologies vs. BDDCS classification

2018 ◽  
Vol 7 (3) ◽  
pp. 358-370 ◽  
Author(s):  
Rosa Chan ◽  
Leslie Z. Benet
Keyword(s):  
Liver Injury ◽  
Drug Development ◽  
Safety Concern ◽  
Drug Induced ◽  
Development Review ◽  
Drug Induced Liver Injury ◽  
Underlying Mechanisms ◽  
Early Drug

Drug-induced liver injury (DILI) is a major safety concern; it occurs frequently; it is idiosyncratic; it cannot be adequately predicted; and a multitude of underlying mechanisms has been postulated.

Sign in / Sign up

Export Citation Format

Share Document