Prediction of human plasma concentration-time profiles of monoclonal antibodies from monkey data by a species-invariant time method.

ABSTRACT

We have previously reported that human total body clearance (CL) and steady-state volume of distribution (Vss) of monoclonal antibodies (mAbs) could be predicted reasonably well from monkey data alone using simple allometry with scaling exponents of 0.79 and 1.12 (for soluble targets), and 0.96 and 1.00 (for membrane-bound targets). In the present study, to predict the plasma concentration-time profiles of mAbs in humans, we employed simple dose-normalization and species-invariant time methods (elementary Dedrick plot and complex Dedrick plot), based on the monkey data and the scaling exponents we previously determined. The results demonstrated that the species-invariant time methods were able to provide higher accuracy of prediction than simple dose-normalization, regardless of the type of target antigens (soluble or membrane-bound). The accuracy between elementary Dedrick plot and complex Dedrick plot was nearly equivalent. The predicted human CL and Vss using species-invariant time methods were within mostly 2-fold differences from the observed values. The prediction not only of pharmacokinetic (PK) parameters but also of the plasma concentration-time profile in humans can serve as guidelines for better planning of clinical studies on mAbs.