Journal
CURRENT PHARMACEUTICAL DESIGN
Volume 10, Issue 24, Pages 2991-3008Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1381612043383494
Keywords
radiolabeled; metabolite profiling; covalent binding; mass balance; absorption; bioavailability; tissue distribution
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Radiolabeled compounds are excellent investigative tools and widely used to carry out ADME studies during drug discovery and development stages. The most commonly used radioisotopes are C-14 and H-3. H-3 materials are generally easier to synthesize than C-14 materials. Therefore, a variety of probes and substrates used in in vitro assays are labeled with H-3. Since synthesis of C-14 material requires intensive resources, it is usually not available until after a molecule is considered for potential development or after the molecule enters the development phase. Improvement in the technology in radiochemistry has enabled the use of radiolabeled compounds earlier in pre-clinical and clinical development to address mechanistic issues. For in vitro studies, radiolabeled probes are utilized to test affinity with various transporters, to perform metabolism comparison among species and to assess possible formation of reactive metabolites. For in vivo studies, radiolabeled compounds are employed to identify and elucidate metabolites formed, to investigate the extent of absorption, bioavailability, tissue distribution, mass balance, routes of excretion, and pre-systemic metabolism. Due to the significant impact of radiolabeled studies on drug development, these studies will be performed earlier than have been in the past and will continue to be an integral part of drug discovery and development.
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