Isotopic tracers for the measurement of metabolic flux rates

Abstract

Human metabolism is comprised of complex networks, and objective and reliable measures (biomarkers) are needed to guide drug developers toward the goals of safe and efficacious outcomes. The combination of stable isotope labeling with sensitive mass spectrometric analytic techniques is providing increasingly important tools for drug development and early phase clinical studies. The use of stable isotopes allows the measurement of fluxes through metabolic pathways in vivo and provides information about what is new within a biological system and how rapidly molecules are being synthesized and degraded in disease physiology and in response to treatment. This chapter describes a selection of applications for the in vivo assessment of lipid, glucose, and lipoprotein metabolic flux using deuterated water and other stable isotopes that can be used effectively in early clinical research studies to study disease pathology and drug efficacy.