Predicting human drug pharmacokinetics from in vitro permeability using an absorption-disposition model.
J Pharm Sci
; 96(8): 2161-70, 2007 Aug.
Article
em En
| MEDLINE
| ID: mdl-17387695
ABSTRACT
The purpose of this research is to simulate the in vivo performance of drugs with a wide range of solubility and permeability characteristics formulated as oral dosage forms. The absorption-disposition model was developed using a number of physiological parameters as well as in vitro permeability data generated with Caco-2 cells, 2/4/A1 cells, and hexadecane membranes. A total of 13 drugs with varying solubility and permeability properties were examined using the absorption-disposition model to predict their pharmacokinetic profile. The correlation of predicted and experimentally determined AUC and Cmax, as measures of the pharmacokinetic profile, were >0.96 for all permeation techniques examined. The predictive ability of the model is influenced by the type of permeation method employed; 2/4/A1 cell data yielded the highest degree of accuracy in predicting Cmax and AUC values. The absorption-disposition model developed in this work accurately predicts the in vivo performance of a wide range of orally administered drugs with 8 of 9 drugs examined falling within 80-125% of the experimental value of AUC when using 2/4/A1 cells.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Farmacocinética
/
Preparações Farmacêuticas
/
Permeabilidade da Membrana Celular
/
Absorção Intestinal
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
J Pharm Sci
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos