PMGK

Bruxelles Woluwe

At the heart of pharmacotherapy is the selection of an appropriate drug, dose and dosing regimen. The rational scientific basis for determining the correct dose for an individual patient relies on the disciplines of PK and PD, and the quantitative evaluation of the dose–concentrations-response relationships. These quantitative approaches embody the concept of pharmacometrics. Pharmacometrics is the science of applying quantitative principles to the interpretation of pharmacological observations. One of its focus is thus the analysis of measurements (metrics) associated with PK and to construct mathematical models to describe and quantify interactions between xenobiotics and patients. The aim of implementing pharmacometrics in our center is thus to describe the time course of drug response in individual subjects, to identify individual factors which predict differences in response, to elucidate drug behavior and to translate those discoveries to the clinic. The final aim is to propose adapted treatments and/or to build dosage algorithms that would allow individualizing and optimizing drug therapies. Central to the area of pharmacometrics is the concept of integrating multiple disciplines such as physiology, pathology, genetics, biology, pharmacology, drug intake, absorption, disposition, and action. This description illustrates the obvious connection with other disciplines. Thus, pharmacometrics is a bridging discipline. More particularly, PK is a very complex aspect of pharmacology and constitutes a basis for pharmacometric modeling. Practically, to be investigated accurately, PK necessitates specific approaches and tools exploring both clinical and experimental aspects of drug PK. The dynamic combination of experimental, fundamental and clinical aspects of PK allows descriptive, explicative and mechanistic investigations that conjointly facilitate new discoveries and contribute to establish the potential usefulness of these discoveries for clinical applications and optimization of pharmacotherapy. These considerations highlight the importance of integrating into one facility both in vitro and in vivo aspects of PK, offering the adequate tools to the researchers to explore multiple tracks that will allow characterizing and understanding deeply and precisely the PK behavior of a given drug and to disentangle the mechanistic aspects. Obviously, an integrated PK platform allows testing unexplored, new or emerging hypotheses.tion and quantification of lipids in biological samples by HPLC-MS (examples include oxysterols, ceramides, endocannabinoids, lysophospholipids, etc).