Genotoxicity Assessment of Drug Metabolites in the Context of MIST and Beyond.
Chem Res Toxicol
; 33(1): 10-19, 2020 01 21.
Article
en En
| MEDLINE
| ID: mdl-31859487
ABSTRACT
While there are dedicated guidelines for industry regarding the assessment of the genotoxic potential of new pharmaceuticals and impurities, and the general safety assessment of major drug metabolites, only limited guidance exists on the assessment of potential genotoxic minor drug metabolites. In this Perspective, we discuss challenges associated with assessing the genotoxic potential of human metabolites and share five case studies within the context of an "aware-avoid-assess" paradigm. A special focus is on a class of potentially genotoxic carcinogens, aromatic amines (arylamines and anilines). This compound class is frequently used as building blocks and may show up as impurities, metabolites, or degradants in pharmaceuticals. We propose several recommendations that should help project teams at different stages of pharmaceutical development. In most cases, proactive interactions with the relevant health authority should be considered to endorse the proposed genotoxicity assessment strategy for minor drug metabolites.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Preparaciones Farmacéuticas
/
Carcinógenos
/
Desarrollo de Medicamentos
/
Mutágenos
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Chem Res Toxicol
Asunto de la revista:
TOXICOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Suiza