Beyond CL and V_SS: A comprehensive approach to human pharmacokinetic predictions

This article presents a comprehensive examination of processes related to the prediction of human pharmacokinetics (PK), a crucial task of clinical drug candidate selection. By systematically incorporating in vitro absorption, distribution, metabolism and excretion (ADME) and in vivo PK data with expert judgement, the study achieves high-quality human PK predictions for 40 orally administered compounds from Boehringer Ingelheim's new chemical entity (NCE) portfolio. Overall, the article provides a detailed evaluation of and guidance for a structured process to predict full concentration-time profiles beyond single-parameter predictions, using state-of-the-art methodologies. Furthermore, it discusses future challenges and improvements, and aims to provide valuable insights for scientists working in drug metabolism and PK (DMPK) or PK/pharmacodynamics (PK/PD) modelling.