A Fully Integrated Assay Panel for Early Drug Metabolism and Pharmacokinetics Profiling.
Assay Drug Dev Technol
; 18(4): 157-179, 2020.
Article
em En
| MEDLINE
| ID: mdl-32407132
ABSTRACT
Evaluation and optimization of physicochemical and metabolic properties of compounds are a crucial component of the drug development process. Continuous access to this information during the design-make-test-analysis cycle enables identification of chemical entities with suitable properties for efficient project progression. In this study, we describe an integrated and automated assay panel (DMPK Wave 1) that informs weekly on lipophilicity, solubility, human plasma protein binding, and metabolic stability in rat hepatocytes and human liver microsomes. All assays are running in 96-well format with ultraperformance liquid chromatography-mass spectrometry (MS)/MS as read-out. A streamlined overall workflow has been developed by optimizing all parts of the process, including shipping of compounds between sites, use of fit-for-purpose equipment and information systems, and technology for compound requesting, data analysis, and reporting. As a result, lead times can be achieved that well match project demands across sites independently of where compounds are synthesized. This robust screening strategy is run on a weekly basis and enables optimization of structure-activity relationships in parallel with DMPK properties to allow efficient and informed decision making.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Preparações Farmacêuticas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Assay Drug Dev Technol
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Suécia