Comparison of Various Approaches to Translate Non-Linear Pharmacokinetics of Monoclonal Antibodies from Cynomolgus Monkey to Human.

European Journal of Drug Metabolism and Pharmacokinetics
Renu SinghDanica Stanimirovic

Abstract

The prediction of pharmacokinetics of monoclonal antibodies (mAbs) exhibiting non-linear pharmacokinetics in preclinical species to human is challenging, and very limited scientific work has been published in this field of research. Therefore, we have conducted an elaborate comparative assessment to determine the most reliable preclinical to clinical scaling strategy for mAbs with non-linear pharmacokinetics. We have compared three different scaling approaches to predict human pharmacokinetics from cynomolgus monkey. In the first approach, cynomolgus monkey pharmacokinetic parameters estimated using a two-compartment model with parallel linear and non-linear elimination were allometrically scaled to simulate human pharmacokinetics. In the second approach, allometric exponents were integrated with a minimal physiologically based pharmacokinetic (mPBPK) model to translate human pharmacokinetics. In the third approach, we have employed a species time-invariant method, wherein a two-compartment model with parallel linear and non-linear elimination was used as a framework model for simulation of the human profile. Human exposure parameters projected by an integrated allometric method were only within two fold for approximately 45-70...Continue Reading

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Citations

Jul 18, 2021·European Journal of Drug Metabolism and Pharmacokinetics·Yichao YuGuo-Fu Li

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