Pharmacometrics
Introduction
Pharmacometrics is the science of interpreting and understanding pharmacology quantitatively. It involves applying mathematical and statistical models to pharmacological data, supporting decision-making in drug development, regulatory submissions, and clinical practice. Moreover, pharmacometrics is used to optimize drug therapy and dosing regimens for diverse patient populations including children, the elderly or patients with specific conditions such as renal or hepatic impairment or cancer. Pharmacometricians use a variety of modeling techniques to simulate clinical trials, reducing the need for expensive and time-consuming clinical or preclinical trials and aiding in the understanding of complex biological systems. Key pharmacometric methods include population pharmacokinetics (PopPK), pharmacokinetics/pharmacodynamics (PK/PD) modeling, and physiologically-based pharmacokinetic (PBPK) modeling. The insights gained from pharmacometric analyses help in optimizing dosing, enhancing drug efficacy, and minimizing adverse effects facilitating more personalized medicine.
Figure 1: Schematics of empirical and mechanistic pharmacometric models and possible applications in early clinical trials. a) Empirical population pharmacokinetic models can be used to identify and explain sources of variability in a drug’s pharmacokinetics. b) Mechanistic modeling approaches, such as physiologically based pharmacokinetic models, provide a preset of compartments for relevant organs and tissues, that can be further split into sub-compartments, allowing the mechanistic implementation of physiological processes. c) Examples for applications of pharmacometric models in early clinical trials 1. Figure adapted from Türk et al. 2. Drawings by Servier, licensed under CC BY 3.0 3. BP: binding protein; CL: clearance; GIT: gastrointestinal tract; Q: inter-compartmental clearance; RBC: red blood cells; V: compartment.
Collaboration
Since 2019, the Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology has published more than 15 articles in close collaboration with the Department of Clinical Pharmacy at Saarland University in high-ranking, peer-reviewed journals in the field of pharmacometrics and clinical pharmacology 2,4,13–18,5–12. These articles answered important research questions, such as the effect of drug-drug and drug-gene interactions on the pharmacokinetics of various small molecules. A “pharmacometrics warehouse” has been established in close collaboration with the Department of Clinical Pharmacy at Saarland University. This warehouse provides guidance in the preclinical and early clinical stages of drug development at the Robert Bosch Centre for Tumour Diseases (RBCT) by developing state-of-the-art pharmacometric models to answer emerging research questions.
