Comprehensive mechanism-based antibody pharmacokinetic modeling.
Annu Int Conf IEEE Eng Med Biol Soc
; 2011: 4318-23, 2011.
Article
en En
| MEDLINE
| ID: mdl-22255295
ABSTRACT
Pharmacokinetic models of antibody distribution and dynamics are useful for predicting and optimizing therapeutic behavior. Targeted antigens are produced and distributed in various tissues in specific patterns in disease phenotypes. Existing models leave out significant mechanistic detail which would enable an understanding of how to modify therapeutics in an optimal manner to allow appropriate tissue penetration in either a healthy or diseased state. The model presented here incorporates additional complexity such as diffusion through endothelial barriers, differential transcytosis properties, FcRn-mediated recycling, and incorporates these properties in an organ-specific manner. This creates a platform which can be expanded upon to include understanding of the effect of target on therapeutic distribution and clearance, differences in dynamics during a diseased versus healthy state, differential dose strategies, and mechanistic translation between animal models and human disease state. This model represents a superior alternative to typical and potentially over-simplified scaling strategies utilized in most existing physiologically-based pharmacokinetic models. Ultimately, this will enable better therapeutic design and greater pharmacological effects.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Farmacocinética
/
Modelos Teóricos
/
Anticuerpos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Annu Int Conf IEEE Eng Med Biol Soc
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos