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

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dc.contributor.authorWotherspoon, ATLen_AU
dc.contributor.authorSafavi-Naeini, Men_AU
dc.contributor.authorBanati, RBen_AU
dc.date.accessioned2025-01-10T03:08:12Zen_AU
dc.date.available2025-01-10T03:08:12Zen_AU
dc.date.issued2017-12en_AU
dc.date.statistics2024-10-29en_AU
dc.description.abstractThis 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.en_AU
dc.format.mediumPrint-Electronicen_AU
dc.identifier.citationWotherspoon, 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-2017-0137en_AU
dc.identifier.issn1757-6180en_AU
dc.identifier.issn1757-6199en_AU
dc.identifier.issue23en_AU
dc.identifier.journaltitleBioanalysisen_AU
dc.identifier.pagination1913-1933en_AU
dc.identifier.urihttps://doi.org/10.4155/bio-2017-0137en_AU
dc.identifier.urihttps://apo.ansto.gov.au/handle/10238/15896en_AU
dc.identifier.volume9en_AU
dc.languageEnglishen_AU
dc.language.isoenen_AU
dc.publisherTaylor & Francisen_AU
dc.subjectDrugsen_AU
dc.subjectIsotopesen_AU
dc.subjectMetabolitesen_AU
dc.subjectSpectroscopyen_AU
dc.subjectPhotonsen_AU
dc.subjectTomographyen_AU
dc.subjectPositronsen_AU
dc.subjectGalliumen_AU
dc.subjectCopperen_AU
dc.subjectFluorineen_AU
dc.subjectCarbonen_AU
dc.subjectMass spectrometersen_AU
dc.subjectMetabolismen_AU
dc.subjectPositron computed tomographyen_AU
dc.subjectRadioisotopesen_AU
dc.titleMicrodosing, isotopic labeling, radiotracers and metabolomics: relevance in drug discovery, development and safetyen_AU
dc.typeJournal Articleen_AU
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