Simplification of complex physiologically based pharmacokinetic models of monoclonal antibodies.

ABSTRACT: Monoclonal antibodies (mAbs) exhibit biexponential profiles in plasma that are commonly described with a standard two-compartment model with elimination from the central compartment. These models adequately describe mAb plasma PK. However, these models ignore elimination from the peripheral compartment. This may lead to underestimation of the volume of distribution of the peripheral compartment and thus over-predicts concentration in the peripheral compartment. We developed a simple and physiologically relevant model that incorporates information on binding and dissociation rates between mAb and FcRn receptor, mAb uptake, reflection, and catabolic degradation. We employed a previously published PBPK model and, with assumptions regarding rates of processes controlling mAb disposition, reduc

SUBMITTER: Elmeliegy M 

PROVIDER: S-EPMC4070266 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature