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Trends of Innovative Clinical Drug Development using AMS (Accelerator Mass Spectrometry) and $^{14}C$-micro Tracer  

Cho, Kyung Hee (Seoul Medical Science Institute/Seoul Clinical Laboratories)
Lee, Hee Joo (BioCore)
Choie, Hyung Sik (BioCore)
Lee, Kyoung Ryul (Seoul Medical Science Institute/Seoul Clinical Laboratories)
Dueker, Stephen R. (Eckert & Ziegler Vitalea Science)
Shin, Young G. (College of Pharmacy, Chungnam National University)
Publication Information
YAKHAK HOEJI / v.57, no.6, 2013 , pp. 412-419 More about this Journal
Abstract
Drug discovery and development processes are time consuming and costly endeavors. It has been reported that on average it takes 10 to 15 years and costs more than $ 1billion to bring a molecule from discovery to market. Compounds fail for various reasons but one of the significant reasons that accounts for failures in clinical trials is poor prediction/understanding of pharmacokinetics and drug metabolism in human. In an effort to improve the number of compounds that exhibit optimal absorption, distribution, metabolism, elimination (ADME), and pharmacokinetic properties in human, drug metabolism, pharmacokinetic scientists have been continually developing new technologies and compound screening strategies. Over the last few years, accelerator mass spectrometry (AMS) and its applications to preclinical/clinical pharmacokinetics and ADME studies have significantly increased, particularly for new chemical/biological entities that are difficult to support with conventional radiolabel studies. In this review, the application of AMS for micro-dosing, micro-tracer absolute bioavailability, mass balance and metabolite profiling studies will be discussed.
Keywords
accelerator mass spectrometry; micro-dosing; absolute bioavailability; mass balance/metabolite profiling; $^{14}C$-micro-tracer;
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1 Dueker, S. R., Sivaraman, L., Wang, J., Wang, L., Fung, N., Maxwell, B., Bonnie, W., Christopher, L., Arnold, M. and McNerney, M. : Placental transfer of a pegylated adnectin in guinea pig (abstract #: 2783), presented poster (http:// www.toxicology.org/AI/PUB/Tox/2012toxsup.pdf).
2 Roffey, S. J., Obach, R. S., Gedge, J. I. and Smith, D. A. : What is the objective of the mass balance study? A retrospective analysis of data in animal and human excretion studies employing radiolabeled drugs. Drug Metab. Rev. 39, 17 (2007).   DOI   ScienceOn
3 Lappin, G., Seymour, M., Gross, G., Jorgensen, M., Kall, M. and Kvaerno, L. : Meeting the MIST regulations: human metabolism in Phase I using AMS and a tiered bioanalytical approach. Bioanalysis 4, 407 (2012).   DOI   ScienceOn
4 Lappin, G. and Stevens, L.: Biomedical accelerator mass spectrometry : recent applications in metabolism and pharmacokinetics. Exp. Opin. Drug Metab.Toxicol. 4, 1021 (2008).   DOI   ScienceOn
5 Salehpour, M., Ekblom, J., Sabetsky, V., Hakansson, K. and Possnert, G. : Accelerator mass spectrometry offers new opportunities for microdosing of peptide and protein pharmaceuticals. Rap. Commun. Mass Spec. 24, 1481 (2010).   DOI   ScienceOn
6 Lappin, G., Seymour, M., Young, G., Higton, D. and Hill, H. M. : AMS method validation for quantitation in pharmacokinetic studies with concomitant extravascular and intravenous administration. Bioanalysis 3, 393 (2011).   DOI   ScienceOn
7 Garner, R. C. : Practical experience of using human microdosing with AMS analysis to obtain early human drug metabolism and PK data. Bioanalysis 2, 429 (2010).   DOI   ScienceOn
8 식품의약품 안전청 : 한국 식약청 마이크로도징 가이드 라인. "의약품의 임상시험 수행과 품목허가를 위한 비임상시험 가이드라인, 2012, 6".
9 Graham, R. A., Lum, B. L., Morrison, G., Chang, I., Jorga, K., Dean, B., Shin, Y. G., Yue, Q., Mulder, T., Malhi, V., Xie, M., Low, J. A. and Hop, C. E. : A single dose mass balance study of the Hedgehog pathway inhibitor vismodigib (GDC-0449) in human using accelerator mass spectrometry. Drug Metab. Dispos. 39, 1460 (2011).   DOI   ScienceOn
10 ICH M3 guidance, http://www.ema.europa.eu/docs/en_GB/ document_li brary/Sci ent i fic_gui deline/2009/09/ WC500002720.pdf.
11 Smith, D. A. : The debate is over : accerelator MS provides the route to better drug-development paradigms/protocols. Bioanalysis 3, 391 (2011).   DOI   ScienceOn
12 Garner, R. C. : Accelerator mass spectrometry in pharmaceutical research and development-a new ultrasensitive analytical method for isotope measurement. Curr. Drug Metab. 1, 205 (2000).   DOI
13 Dueker, S. R., Vuong, L. T., Lohstroh, P. N., Giacomo, J. A. and Vogel, J. S. : Quantifying exploratory low dose compounds in humans with AMS. Adv. Drug Del. Rev. 63, 518 (2011).   DOI   ScienceOn
14 Schulze-Koenig, T., Dueker, S. R., Giacomo, J., Suter, M., Vogel, J. S. and Synal, H. : BioMICADAS : Compact next generation AMS system for pharmaceutical science. Nuclear Instr. and Methods in Physics Res. sect B : Beam interactions with Materials and Atoms 268, 891 (2010).   DOI   ScienceOn
15 Lappin, G. and Garner, R. C. : Current perspectives of 14Cisotope measurement in biomedical accelerator mass spectrometry. Anal. Bioanal. Chem. 378, 356 (2004).   DOI   ScienceOn
16 FDA 2004 critical path initiative, http://www.fda.gov/ ScienceResearch/SpecialTopics/CriticalPathInitiative/ ucm076689.htm.
17 Madan, A., O'Brien, Z., Wen, J., O'Brien, C., Farber, R. H., Beaton, G., Crowe, P., Oosterhuis, B., Garner, R. C., Lappin, G. and Bozigian, H. P. : A Pharmacokinetic evaluation of five H(1) antagonists after an oral and intravenous microdose to human subjects. Br. J. Clin. Pharmacol. 67, 288 (2009).   DOI   ScienceOn
18 Ings, R. M. J. : Microdosing : a valuable tool for accelerating drug development and the role of bioanalytical methods in meeting the challenge. Bioanalysis 1, 1293 (2009).   DOI   ScienceOn
19 Lappin, G., Seymour, M., Young, G., Higton, D. and Hill, H. M. : An AMS method to determine analyte recovery from pharmacokinetic studies with concomitant extravascular and intravenous administration. Bioanalysis 3, 407 (2011).   DOI   ScienceOn
20 Lappin, G., Wagner, C. C., Langer, O. and Van de Merbel, N. : New Ultrasensitive detection technologies and techniques for use in microdosing studies. Bioanalysis 1, 357 (2009).   DOI   ScienceOn
21 Allison, M. : Reinventing clinical trials. Nat. Biotechnol. 30, 41 (2012).   DOI   ScienceOn
22 U.S. Food and drug administration : FDA MIST guidance, http://www.fda.gov/downloads/Drugs/GuidanceCompliance RegulatoryInformation/Guidances/ucm079266.pdf.
23 Paul, S. M., Mytelka, D. S., Dunwiddie, C. T., Persinger, C. C., Munos, B. H., Lindborg, S. R. and Schacht, A. L. : How to improve R&D productivity : the pharmaceutical industry's grand challenge. Nat. Rev. Drug Discov. 9, 203 (2010).
24 Graham, R. A., Hop, C. E., Borin, M. T., Lum, B. L., Colburn, D., Chang, I., Shin, Y. G., Malhi, V., Low. J. A. and Dresser, M. J. : Single and multiple dose intravenous and oral pharmakinetics of the hedgehog pathway inhibitor vismodegib in healthy female subjects. Br. J. Clin. Pharmocol. 74, 788 (2012).   DOI   ScienceOn
25 Bae, S. K. and Shon, J. : Microdosing studies using accelerated mass spectrometry as exploratory investigational new drug trials. Arch. Pharm. Res. 34, 1789 (2011).   DOI
26 Lappin, G. and Seymour, M. : Addressing metabolite safety during first-in-man studies using 14C-labeled drug and accelerator mass spectrometry. Bioanalysis 2, 1315 (2010).   DOI   ScienceOn