Knowledge of human concentration-time profiles from animal data can be useful during early drug development. The objective of this study is to predict human concentration-time profiles of antibody-drug conjugates (ADCs) and subsequently predict pharmacokinetic parameters in humans from rats or monkeys. Eight methods with different exponents of volume of distribution (0.8-1) as well as exponents of clearance (0.85), along with the exponents of volume of distribution for 5 ADCs, were used to predict human concentration-time profiles. The PK parameters were also scaled to humans from monkeys or rats using fixed exponents and compared with the PK parameters predicted from predicted human concentration-time profiles. The results of the study indicated that the exponent 0.9 and the combination of exponents of 0.9 and 0.8 (two exponents, 0.8 and 0.9, were used) were the best method to predict human concentration-time profiles and, subsequently, human PK parameters. The predicted PK parameters from fixed exponents were comparable with the predicted PK parameters estimated from human concentration-time profiles. The proposed methods are applicable to rats or monkeys with the same degree of accuracy. Overall, the proposed methods are robust, accurate, and cost- and time-effective.
Keywords: ADCs; fixed exponent scaling; human concentration–time profiles; pharmacokinetics.