Physiologically Based Pharmacokinetic Modelling for First-In-Human Predictions: An Updated Model Building Strategy Illustrated with Challenging Industry Case Studies

摘要: Physiologically based pharmacokinetic modelling is well established in the pharmaceutical industry and accepted by regulatory agencies for prediction of drug–drug interactions. However, physiologically valuable to address a much wider range applications, new impact expected as its full power leveraged. As one example, already routinely used during drug discovery in-vitro in-vivo translation preclinical species, this leads application verified models first-in-human predictions. A consistent cross-industry strategy area would increase confidence approach facilitate further learning. With mind, article aims enhance previously published model-building strategy. Based on experience scientists from multiple companies participating GastroPlus™ User Group Steering Committee, Absorption, Distribution, Metabolism Excretion knowledge integrated decision trees proposed each essential component prediction. We have reviewed many relevant scientific publications identify findings highlight gaps that need be addressed. Finally, four case studies more challenging compounds illustrate key components