Báo cáo y học: " Assessing drug distribution in tissues expressing P-glycoprotein through physiologically based pharmacokinetic modeling: model structure and parameters determination" pps
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Cấu trúc
Abstract
Background
Methods
Results
Conclusion
Background
Methods
Structure of the PBPK model
Tissue-distribution models
Well-stirred model (WS)
Mechanistic Transport-Based (MTB) models
Mouse-related parameters
Distribution-related parameters required for the MTB model
Step I: Estimation of in vitro diffusion and P-gp efflux rates of a P-gp substrate through Caco-2 monolayer
Step II: In vitro-in vivo extrapolation of drug diffusion velocity and P-gp efflux rate parameters
Step III: Calculation of the permeability-surface area product (PSAt) and P-gp-mediated efflux clearance (CLP-gp, t) of the P-gp substrate into mice brain and heart
Assessing drug distribution in tissues expressing P-gp
Results
Estimation of metabolic parameters
Estimation of distribution parameters for WS and MTB models
WS Model
MTB Models: Accounting only for P-gp Efflux Activity in Heart and Brain