Practical permeability-based hepatic clearance classification system (HepCCS) in drug discovery.
Future Med Chem
; 6(18): 1995-2012, 2014.
Article
em En
| MEDLINE
| ID: mdl-25531965
ABSTRACT
BACKGROUND:
The use of liver microsomes and hepatocytes to predict total in vivo clearance is standard practice in the pharmaceutical industry; however, metabolic stability data alone cannot always predict in vivo clearance accurately.RESULTS:
Apparent permeability generated from Mardin-Darby canine kidney cells and rat hepatocyte uptake for 33 discovery compounds were obtained.CONCLUSION:
When there is underprediction of in vivo clearance, compounds with low apparent permeability (less than 3 × 10(-6) cm/s) all exhibited hepatic uptake. A systematic approach in the form of a classification system (hepatic clearance classification system) and decision tree that will help drug discovery scientists understand in vitro-in vivo clearance prediction disconnect early is proposed.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Preparações Farmacêuticas
/
Hepatócitos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Future Med Chem
Ano de publicação:
2014
Tipo de documento:
Article