A Physiologically-Based Pharmacokinetic Model for the Prediction of "Half-Life Extension" and "Catch and Release" Monoclonal Antibody Pharmacokinetics.

ABSTRACT: Monoclonal antibodies (mAbs) can be engineered to have "extended half-life" and "catch and release" properties to improve target coverage. We have developed a mAb physiologically-based pharmacokinetic model that describes intracellular trafficking, neonatal Fc receptor (FcRn) recycling, and nonspecific clearance of mAbs. We extended this model to capture target binding as a function of target affinity, expression, and turnover. For mAbs engineered to have an extended half-life, the model was able to accurately predict the terminal half-life (82% within 2-fold error of the observed value) in the human FcRn transgenic (Tg32) homozygous mouse and human. The model also accurately captures the trend in pharmacokinetic and target coverage data for a set of mAbs with differing catch and release p

SUBMITTER: Jones HM 

PROVIDER: S-EPMC7499188 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature