The Critical Role of Passive Permeability in Designing Successful Drugs.
ChemMedChem
; 15(20): 1862-1874, 2020 10 19.
Article
en En
| MEDLINE
| ID: mdl-32743945
ABSTRACT
Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as inâ
vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Preparaciones Farmacéuticas
/
Membrana Celular
/
Permeabilidad de la Membrana Celular
Límite:
Animals
/
Humans
Idioma:
En
Revista:
ChemMedChem
Asunto de la revista:
FARMACOLOGIA
/
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos