Predicting Human Bioavailability of Subcutaneously Administered Fusion Proteins and Monoclonal Antibodies Using Human Intravenous Clearance or Antibody Isoelectric Point

In this study, we explored the relationships between human SC bioavailability and physicochemical or pharmacokinetic properties of 19 Fc- or albumin-fusion proteins and 98 monoclonal antibodies. An inverse linear correlation was observed between human SC bioavailability and intravenous clearance (CL) or isoelectric point (pI). Multivariate regression models were developed using intravenous CL and pI of a training set (N = 59) as independent variables. The predictive models of mAbs were validated with an independent test set (N = 33). Two linear regression models resulted in 24 (73%) and 27 (82%) among 33 predictions within 0.8- to 1.2-fold deviations. Due to the small sample size of dataset, regression model validation was not conducted for fusion proteins. Overall, this study demonstrated that CL- and pI-based multi variate regression models could be used to predict human SC bioavailability of mAbs.Graphical Abstract
Source: The AAPS Journal - Category: Drugs & Pharmacology Source Type: research