Microdosing, isotopic labeling, radiotracers and metabolomics: relevance in drug discovery, development and safety

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Date
2017-12
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Taylor & Francis
Abstract
This review discusses the use of stable (13C, 2D) or radioactive isotopes (14C,11C, 18F, 131I, 64Cu, 68Ga) incorporated into the molecular structure of new drug entities for the purpose of pharmacokinetic or -dynamic studies. Metabolite in safety testing requires the administration of pharmacologically active doses. In such studies, radiotracers find application mainly in preclinical animal investigations, whereby LC-MS/MS is used to identify metabolite structure and drug-related effects. In contrast, first-in-human metabolite studies have to be carried out at nonpharmacological doses not exceeding 100 μg (microdose), which is generally too low for metabolite detection by LC-MS/MS. This short-coming can be overcome by specific radio- or isotopic labeling of the drug of interest and measurements using accelerator mass spectroscopy, single-photon emission computed tomography and positron emission tomography. Such combined radioisotope-based approaches permit Phase 0, first-in-human metabolite study. © 2024Informa UK Limited. This work is licensed under a Crown Copyright protection and licensed for use under the Open Government License unless otherwise indicated. Where any of the Crown copyright information in this work is republished or copied to others, the source of the material must be identified and the copyright status under the Open Government License acknowledged.
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Drugs, Isotopes, Metabolites, Spectroscopy, Photons, Tomography, Positrons, Gallium, Copper, Fluorine, Carbon, Mass spectrometers, Metabolism, Positron computed tomography, Radioisotopes
Citation
Wotherspoon, A. T. L., Safavi-Naeini, M., & Banati, R. B. (2017). Microdosing, isotopic labeling, radiotracers and metabolomics: relevance in drug discovery, development and safety. Bioanalysis, 9(23), 1913-1933. doi:10.4155/bio-2017-0137
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https://doi.org/10.4155/bio-2017-0137
 https://apo.ansto.gov.au/handle/10238/15896
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