Accelerating drug development: methodology to support first-in-man pharmacokinetic studies by the use of drug candidate microdosing

2007 ◽  
Vol 68 (1) ◽  
pp. 14-22 ◽  
Author(s):  
Matthew A. McLean ◽  
Chi-Yan J. Tam ◽  
Michael T. Baratta ◽  
Christopher L. Holliman ◽  
Robert M. Ings ◽  
...  
Keyword(s):  
Drug Development ◽  
Drug Candidate ◽  
Pharmacokinetic Studies ◽  
Development Methodology

scholarly journals Has molecular imaging delivered to drug development?

2017 ◽  
Vol 375 (2107) ◽  
pp. 20170112 ◽  
Author(s):  
Philip S. Murphy ◽  
Neel Patel ◽  
Timothy J. McCarthy
Keyword(s):  
Molecular Imaging ◽  
Drug Development ◽  
Clinical Studies ◽  
Pharmaceutical Research ◽  
Whole Body ◽  
Drug Candidate ◽  
Clinical Drug Development ◽  
Target Binding ◽  
The Brain ◽  
Clinical Drug

Pharmaceutical research and development requires a systematic interrogation of a candidate molecule through clinical studies. To ensure resources are spent on only the most promising molecules, early clinical studies must understand fundamental attributes of the drug candidate, including exposure at the target site, target binding and pharmacological response in disease. Molecular imaging has the potential to quantitatively characterize these properties in small, efficient clinical studies. Specific benefits of molecular imaging in this setting (compared to blood and tissue sampling) include non-invasiveness and the ability to survey the whole body temporally. These methods have been adopted primarily for neuroscience drug development, catalysed by the inability to access the brain compartment by other means. If we believe molecular imaging is a technology platform able to underpin clinical drug development, why is it not adopted further to enable earlier decisions? This article considers current drug development needs, progress towards integration of molecular imaging into studies, current impediments and proposed models to broaden use and increase impact. This article is part of the themed issue ‘Challenges for chemistry in molecular imaging’.

scholarly journals Challenges of Psychiatry Drug Development and the Role of Human Pharmacology Models in Early Development—A Drug Developer's Perspective

2021 ◽  
Vol 11 ◽  
Author(s):  
Tong Zhu
Keyword(s):  
Drug Development ◽  
Drug Exposure ◽  
Phase 1 ◽  
Drug Candidate ◽  
Phase 2 ◽  
Medical Needs ◽  
Clinical Drug Development ◽  
Human Pharmacology ◽  
Exposure Target ◽  
Target Binding

Psychiatric diseases have the lowest probability of success in clinical drug development. This presents not only an issue to address the unmet medical needs of patients, but also a hurdle for pharmaceutical and biotech industry to continue R&D in this disease area. Fundamental pharmacokinetic and pharmacodynamic principles provide an understanding of the drug exposure, target binding and pharmacological activity at the target site of action for a new drug candidate. Collectively, these principles determine the likelihood of testing the mechanism of action and enhancing the likelihood of candidate survival in Phase 2 clinical development, therefore, they are termed as the “three pillars of survival.” Human Phase 1 pharmacokinetic and pharmacodynamic studies provide evidence of the three pillars. Electroencephalogram (EEG) assessments and cognitive function tests in schizophrenia patients can provide proof of pharmacology and ensure that a pharmacological active regimen will be tested in Phase 2 proof of concept (POC) studies for the treatment of cognitive impairment associated with schizophrenia (CIAS).

scholarly journals Biomedical Graph Visualizer for Identifying Drug Candidates

2020 ◽  
Author(s):  
Ashton Teng ◽  
Blanca Villanueva ◽  
Derek Jow ◽  
Shih-Cheng (Mars) Huang ◽  
Samantha N. Piekos ◽  
...  
Keyword(s):  
Drug Development ◽  
De Novo ◽  
Drug Candidate ◽  
Knowledge Graph ◽  
Major Barrier ◽  
Drug Candidates ◽  
Novel Treatments ◽  
Computational Discovery ◽  
Complex Relationships ◽  
User Friendly

1.AbstractMillions of Americans suffer from illnesses with non-existent or ineffective drug treatment. Identifying plausible drug candidates is a major barrier to drug development due to the large amount of time and resources required; approval can take years when people are suffering now. While computational tools can expedite drug candidate discovery, these tools typically require programming expertise that many biologists lack. Though biomedical databases continue to grow, they have proven difficult to integrate and maintain, and non-programming interfaces for these data sources are scarce and limited in capability. This creates an opportunity for us to present a suite of user-friendly software tools to aid computational discovery of novel treatments through de novo discovery or repurposing. Our tools eliminate the need for researchers to acquire computational expertise by integrating multiple databases and offering an intuitive graphical interface for analyzing these publicly available data. We built a computational knowledge graph focused on biomedical concepts related to drug discovery, designed visualization tools that allow users to explore complex relationships among entities in the graph, and served these tools through a free and user-friendly web interface. We show that users can conduct complex analyses with relative ease and that our knowledge graph and algorithms recover approved repurposed drugs. Our evaluation indicates that our method provides an intuitive, easy, and effective toolkit for discovering drug candidates. We show that our toolkit makes computational analysis for drug development more accessible and efficient and ultimately plays a role in bringing effective treatments to all patients.Our application is hosted at: https://biomedical-graph-visualizer.wl.r.appspot.com/

scholarly journals Bioanalysis and pharmacokinetic studies

2020 ◽  
pp. IPK01
Author(s):  
Maria Veneziano
Keyword(s):  
Drug Discovery ◽  
Small Molecules ◽  
Bioanalytical Methods ◽  
High Resolution Mass Spectrometry ◽  
Drug Candidate ◽  
Pharmacokinetic Studies ◽  
Inborn Errors ◽  
Drug Discovery Program

Biography: Maria Veneziano is currently a Research Investigator in the DMPK unit at IRBM (Pomezia, Italy), an Italian CRO and biotech company specializing in preclinical drug discovery of small molecules, peptides and antibodies. She studied Biological Science at ‘Federico II’ University of Naples (Italy) and completed her PhD in Medical Biotechnologies at Merck Research Laboratories (MRL) in Rome (Italy) developing bioanalytical methods used to identify and quantify amino acids and acylcarnitines for the diagnosis and follow-up of inborn errors of metabolism. As part of the DMPK team at MRL, she was involved in PK and ADME profiling of small molecule and peptide candidates for drug-discovery programs. Presently, Maria leads a group supporting PK and PK/PD studies for small molecules and peptides. Maria Veneziano speaks to the International Journal of Pharmacokinetics about her experience working on pharmacokinetic studies. She starts by discussing the conventional bioanalytical methods used for the quantitative analysis of small molecules and peptides and she highlights the important role of LC–MS detection and sample preparation in the bioanalysis of pharmacokinetic studies. She also speaks about the role of high-resolution mass spectrometry in the bioanalysis of peptides as an important tool in a drug-discovery program to simultaneously define pharmacokinetic and metabolic profiles of the same drug candidate. She also describes cassette dosing and cassette analysis approaches as strategies to increase sample throughput, highlighting advantages and limits of each of these strategies. Finally, Maria speaks about her idea of ‘simplified PK workflow’ based on the miniaturization and automation of all the steps in a PK study, from in vivo administration to sample analysis.

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