Knowledge of biochemical flux (or pathway activity) is required for elements of PK/PD modeling and yields new knowledge regarding interactions surrounding pharmacological networks. Mass spec analyses can be coupled with stable isotope tracer protocols to support nearly all stages of drug development, from early discovery biology to late-stage exposure-response predictions. Tracer protocols and related analyses need to fit within constraints of the biological system under investigation. Half-life of precursor (probe) and product (endpoint of interest) need alignment, as well as alignment with resource request to execute a study and conduct requisite analyses. It is possible to enable decision making with regards to IVIVC, elucidate mechanism of action, and guide dose prediction. These methods can be applied regardless of modality and/or biological system.
Learning Objectives:
Describe the use of isotope tracers to unravel target kinetics.
Understand the experimental challenges associated with designing kinetic experiments.
Gauge application of the approach to elucidation of mechanism of action, guiding of dose selection, etc.
