Scientific Publications by FDA Staff

Regul Toxicol Pharmacol 2018 Aug;97:57-62

Prediction of tissue concentrations of monoclonal antibodies in mice from plasma concentrations.

Mahmood I, Tegenge MA

The objectives of this study were to develop and evaluate allometric methods for predicting tissue-to-plasma partition coefficients (Kp) in mice from experimentally determined in-vivo volume of distribution at steady state (Vss) for monoclonal antibodies (mAbs). The Vss was allometrically predicted (using a fixed exponent 1.0 or 0.9) in a given tissue of the mice. The Kp was predicted using Vss and tissue specific physiological parameters. In total, Kp values were predicted for 20 mAbs, 121 tissues, and 665 tissue concentrations. The predicted Kp values and tissue concentrations were compared with the experimental results as well as an empirically predicted antibody biodistribution coefficient (ABC). Comparison of the predicted Kp values by the two proposed methods with experimentally determined Kp values indicated that 64-75% of the predicted Kp values were within two-fold prediction error. For 665 tissue concentrations, 63%, 74%, and 48% tissue concentration ratio were within 0.5-2 fold prediction error by exponent 1.0, exponent 0.9, and ABC, respectively. The proposed allometric methods are better than ABC method for the prediction of tissue Kp values and tissue concentrations. The proposed methods can reasonably predict tissue concentrations of mAbs using plasma concentration gathered at early stage of biologics development.