Clinical Pharmacology – Biomolecular
2019 PharmSci 360
For indications where it is either infeasible or unethical to run clinical trials in humans, it becomes necessary to find methodologies translate the results obtained in animal models to human outcomes. To predict the survival benefits of G-CSF treatment in the acute radiation syndrome (ARS) indication, data collated from several sources was utilized: pegfilgrastim or filgrastim PK, absolute neutrophil count (ANC) response from 10 clinical trials of adults (healthy volunteers and cancer patients) and pediatric cancer patients; as well as data from pivotal trials of ARS in non-human primates (NHPs). This session will cover the integration of all the data using mechanistic modeling of PK and granulopoiesis in humans in the cancer-induced neutropenia setting (CIN), the mechanistic modeling of ARS (injury and neutropenia) in NHPs, and modeling of overall survival in NHPs. Finally, a methodology will be presented for combining these models to predict the survival benefit to humans of G-CSF treatment in the ARS setting.