TY  - JOUR
A1  - Fronton, Ludivine
A1  - Pilari, Sabine
A1  - Huisinga, Wilhelm
T1  - Monoclonal antibody disposition: a simplified PBPK model and its implications for the derivation and interpretation of classical compartment models
JF  - Journal of pharmacokinetics and pharmacodynamics
N2  - The structure, interpretation and parameterization of classical compartment models as well as physiologically-based pharmacokinetic (PBPK) models for monoclonal antibody (mAb) disposition are very diverse, with no apparent consensus. In addition, there is a remarkable discrepancy between the simplicity of experimental plasma and tissue profiles and the complexity of published PBPK models. We present a simplified PBPK model based on an extravasation rate-limited tissue model with elimination potentially occurring from various tissues and plasma. Based on model reduction (lumping), we derive several classical compartment model structures that are consistent with the simplified PBPK model and experimental data. We show that a common interpretation of classical two-compartment models for mAb disposition-identifying the central compartment with the total plasma volume and the peripheral compartment with the interstitial space (or part of it)-is not consistent with current knowledge. Results are illustrated for the monoclonal antibodies 7E3 and T84.66 in mice.
KW  - mAb disposition
KW  - PBPK
KW  - Extravasation rate-limited tissue model
KW  - Classical compartment model
Y1  - 2014
U6  - https://doi.org/10.1007/s10928-014-9349-1
SN  - 1567-567X
SN  - 1573-8744
VL  - 41
IS  - 2
SP  - 87
EP  - 107
PB  - Springer
CY  - New York
ER  -