Role of Clinical Pharmacokinetics Studies in Contemporary Oncology Drug Development

Abstract

Pharmacokinetics (PK) studies enable drug developers to elucidate the relationship of dose to blood concentrations of drugs in various patient populations and determining the need for dose adjustment based on PK differences among demographic subgroups or subgroups with impaired elimination. PK studies also provide the basis for therapeutic drug monitoring in rare patient populations or when effective drugs with very narrow safe therapeutic windows must be used. Population PK studies are aimed at optimizing the dose and schedule by identifying the factors that alter the dose-concentration relationship and determining if such alterations change the therapeutic index using a data-driven approach and integrated sources of information. The clinical importance of identifying and implementing optimum dosing strategies has led to increased application of the population PK strategies in early oncology clinical trials. Multi-scale mechanistic PK models have been developed in an attempt to better predict the clinical performance of the oncology drug candidates. F. M. Uckun (*) AresMIT Biomedical Computational Strategies (ABCS), Minneapolis, MN, USA Ares Pharmaceuticals, St. Paul, MN, USA e-mail: [email protected]; [email protected] S. Qazi AresMIT Biomedical Computational Strategies (ABCS), Minneapolis, MN, USA Ares Pharmaceuticals, St. Paul, MN, USA Bioinformatics Program, Gustavus Adolphus College, St. Peter, MN, USA e-mail: [email protected] # Springer Nature Switzerland AG 2019 F. J. Hock, M. R. Gralinski (eds.), Drug Discovery and Evaluation: Methods in Clinical Pharmacology, https://doi.org/10.1007/978-3-319-56637-5_24-1 1 Over the last two decades PK studies have increasingly become an integral part of early clinical development of promising oncology drugs entering the clinical space. Of the total of 4,481 interventional clinical oncology trials with integrated PK studies registered in the clinicaltrials.gov data repository that were initiated within the 24-year time interval between 1994 and 2018, ~60% of the clinical PK studies were initiated within the last 8 years.