The application of human phase 0 microdosing trials: A systematic review and perspectives

References

• FDA. Innovation or stagnation: challenges and opportunity on the critical path to new medical products. MD: U.S. Department of Health and Human Services, Food and Drug Administration; 2004 Available from: http://www.fda.gov/downloads/ScienceResearch/SpecialTopics/CriticalPathInitiative/CriticalPathOpportunitiesReports/ucm113411.pdf. Accessed August 5, 2014.
   Google Scholar
• EMEA. Position paper on non-clinical safety studies to support clinical trials with a single microdose. Position paper:CPMP/SWP2599. London: Committee for medicinal products for human use (CHMP); 2004. Available from: http://www.tga.gov.au/pdf/euguide/swp259902r1en.pdf. Accessed July 11, 2014.
   Google Scholar
• FDA. Guidance for Industry, Investigators, and Reviewers: exploratory IND Studies. MD: U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER); 2006. Available from: http://www.fda.gov/OHRMS/DOCKETS/98fr/05d–0122–gdl0002.pdf. Accessed July 11, 2014.
   Google Scholar
• International Conference on Harmonisation. ICH guideline M3(R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals. December 2009.
   Google Scholar
• Lappin G, Garner RC. A review of human phase 0 (microdosing) clinical trials following the US food and drug administration exploratory investigational new drug studies guidance. Int J Pharm Med 2006; 20: 159–165.
   Google Scholar
• Lappin G, Garner RC. Big physics, small doses: the use of AMS and PET in human microdosing of development drugs. Nat Rev Drug Discov 2003; 2: 233–240.
   PubMed Web of Science ®Google Scholar
• Maeda K, Sugiyama Y. Novel strategies for microdose studies using non-radiolabeled compounds. Adv Drug Deliv Rev 2011; 63: 532–538.
   PubMed Web of Science ®Google Scholar
• Aalborg University Hospital. Microdose study of melphalan, bortezomib and dexamethasone (Phase-0-MM) In: ClinicalTrials.gov [Internet]. Bethesda, MD: National Library of Medicine; 2000. Available from: http://clinicaltrials.gov/show/NCT0209861 NLM Identifier: NCT0209861. Accessed July 15, 2015.
   Google Scholar
• Gordi T, Baillie R, Vuong le T, et al. Pharmacokinetic analysis of 14C-ursodiol in newborn infants using accelerator mass spectrometry. J Clin Pharmacol 2014; 54: 1031–1037.
   PubMed Web of Science ®Google Scholar
• Cahn A, Hodgson S, Wilson R, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics of GSK2239633, a CC-chemokine receptor 4 antagonist, in healthy male subjects: Results from an open-label and from a randomised study. BMC Pharmacol Toxicol 2013; 14:14.
   PubMed Web of Science ®Google Scholar
• Heuveling DA, de Bree R, Vugts DJ, et al. Phase 0 microdosing PET study using the human mini antibody F16SIP in head and neck cancer patients. J Nucl Med 2013; 54: 397–401.
   PubMed Web of Science ®Google Scholar
• Kuwano K, Hashino A, Asaki T, et al. 2-{4-[(5,6-Diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl) acetamide (NS-304), an orally available and long–acting prostacyclin receptor agonist prodrug. J Pharmacol Exp Ther 2007; 322: 1181–1188.
   PubMed Web of Science ®Google Scholar
• Ostenfeld T, Beaumont C, Bullman J, et al. Human microdose evaluation of the novel EP1 receptor antagonist GSK269984A. Br J Clin Pharmacol 2012; 74: 1033–1044.
   PubMed Web of Science ®Google Scholar
• Chen J, Garner RC, Lee LS, et al. Accelerator mass spectrometry measurement of intracellular concentrations of active drug metabolites in human target cells in vivo. Clin Pharmacol Ther 2010; 88: 796–800.
   PubMed Web of Science ®Google Scholar
• Cho DY, Bae SH, Shon JH, Bae SK. High-sensitive LC-MS/MS method for the simultaneous determination of mirodenafil and its major metabolite, SK-3541, in human plasma: Application to microdose clinical trials of mirodenafil. J Sep Sci 2013; 36: 840–848.
   PubMed Web of Science ®Google Scholar
• Harrison A, Gardner I, Hay T, et al. Case studies addressing human pharmacokinetic uncertainty using a combination of pharmacokinetic simulation and alternative first in human paradigms. Xenobiotica 2012; 42: 57–74.
   PubMed Web of Science ®Google Scholar
• Sun L, Li H, Willson K, et al. Ultrasensitive liquid chromatography-tandem mass spectrometric methodologies for quantification of five HIV-1 integrase inhibitors in plasma for a microdose clinical trial. Anal Chem 2012; 84: 8614–8621.
   PubMed Web of Science ®Google Scholar
• Yamazaki A, Kumagai Y, Yamane N, et al. Microdose study of a P-glycoprotein substrate, fexofenadine, using a non-radioisotope-labelled drug and LC/MS/MS. J Clin Pharm Ther 2010; 35: 169–175.
   PubMed Web of Science ®Google Scholar
• Yamane N, Tozuka Z, Sugiyama Y, et al. Microdose clinical trial: quantitative determination of fexofenadine in human plasma using liquid chromatography/electrospray ionization tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2007; 858: 118–128.
   PubMed Web of Science ®Google Scholar
• Chen J, Flexner C, Liberman RG, et al. Biphasic elimination of tenofovir diphosphate and nonlinear pharmacokinetics of zidovudine triphosphate in a microdosing study. J Acquir Immune Defic Syndr 2012; 61: 593–599.
   PubMed Web of Science ®Google Scholar
• Ikeda T, Aoyama S, Tozuka Z, et al. Microdose pharmacogenetic study of 14C-tolbutamide in healthy subjects with accelerator mass spectrometry to examine the effects of CYP2C9 *3 on its pharmacokinetics and metabolism. Eur J Pharm Sci 2013; 49: 642–648.
   PubMed Web of Science ®Google Scholar
• Wagner CC, Simpson M, Zeitlinger M, et al. A combined accelerator mass spectrometry-positron emission tomography human microdose study with 14C- and 11C-labelled verapamil. Clin Pharmacokinet 2011; 50: 111–120.
   PubMed Web of Science ®Google Scholar
• Ieiri I, Doi Y, Maeda K, et al. Microdosing clinical study: Pharmacokinetic, pharmacogenomic (SLCO2B1), and interaction (grapefruit juice) profiles of celiprolol following the oral microdose and therapeutic dose. J Clin Pharmacol 2012; 52: 1078–1089.
   PubMed Web of Science ®Google Scholar
• Maeda K, Takano J, Ikeda Y, et al. Nonlinear pharmacokinetics of oral quinidine and verapamil in healthy subjects: a clinical microdosing study. Clin Pharmacol Ther 2011; 90: 263–270.
   PubMed Web of Science ®Google Scholar
• Gao L, Li J, Kasserra C, et al. Precision and accuracy in the quantitative analysis of biological samples by accelerator mass spectrometry: application in microdose absolute bioavailability studies. Anal Chem 2011; 83: 5607–5616.
   PubMed Web of Science ®Google Scholar
• Zhou XJ, Garner RC, Nicholson S, et al. Microdose pharmacokinetics of IDX899 and IDX989, candidate HIV-1 non-nucleoside reverse transcriptase inhibitors, following oral and intravenous administration in healthy male subjects. J Clin Pharmacol 2009; 49: 1408–1416.
   PubMed Web of Science ®Google Scholar
• Lappin G, Shishikura Y, Jochemsen R, et al. Comparative pharmacokinetics between a microdose and therapeutic dose for clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen), and phenobarbital in human volunteers. Eur J Pharm Sci 2011; 43: 141–150.
   PubMed Web of Science ®Google Scholar
• Lappin G, Shishikura Y, Jochemsen R, et al. Pharmacokinetics of fexofenadine: evaluation of a microdose and assessment of absolute oral bioavailability. Eur J Pharm Sci 2010; 40: 125–131.
   PubMed Web of Science ®Google Scholar
• Lappin G, Boyce MJ, Matzow T, et al. A microdose study of 14C-AR-709 in healthy men: Pharmacokinetics, absolute bioavailability and concentrations in key compartments of the lung. Eur J Clin Pharmacol 2013; 69: 1673–1682.
   PubMed Web of Science ®Google Scholar
• Madan A, O'Brien Z, Wen J, et al. A pharmacokinetic evaluation of five H1 antagonists after an oral and intravenous microdose to human subjects. Br J Clin Pharmacol 2009; 67: 288–298.
   PubMed Web of Science ®Google Scholar
• Barthel H, Luthardt J, Becker G, et al. Individualized quantification of brain beta-amyloid burden: results of a proof of mechanism phase 0 florbetaben PET trial in patients with Alzheimer's disease and healthy controls. Eur J Nucl Med Mol Imaging 2011; 38: 1702–1714.
   PubMed Web of Science ®Google Scholar
• Bauer M, Langer O, Dal-Bianco P, et al. A positron emission tomography microdosing study with a potential antiamyloid drug in healthy volunteers and patients with Alzheimer's disease. Clin Pharmacol Ther 2006; 80: 216–227.
   PubMed Web of Science ®Google Scholar
• Kaplan N, Garner C, Hafkin B. AFN-1252 in vitro absorption studies and pharmacokinetics following microdosing in healthy subjects. Eur J Pharm Sci 2013; 50: 440–446.
   PubMed Web of Science ®Google Scholar
• Kusuhara H, Ito S, Kumagai Y, et al. Effects of a MATE protein inhibitor, pyrimethamine, on the renal elimination of metformin at oral microdose and at therapeutic dose in healthy subjects. Clin Pharmacol Ther 2011; 89: 837–844.
   PubMed Web of Science ®Google Scholar
• Tozuka Z, Kusuhara H, Nozawa K, et al. Microdose study of 14 c-acetaminophen with accelerator mass spectrometry to examine pharmacokinetics of parent drug and metabolites in healthy subjects. Clin Pharmacol Ther 2010; 88: 824–830.
   PubMed Web of Science ®Google Scholar
• Croft M, Keely B, Morris I, et al. Predicting drug candidate victims of drug-drug interactions, using microdosing. Clin Pharmacokinet 2012; 51: 237–246.
   PubMed Web of Science ®Google Scholar
• Maeda K, Ikeda Y, Fujita T, et al. Identification of the rate-determining process in the hepatic clearance of atorvastatin in a clinical cassette microdosing study. Clin Pharmacol Ther 2011; 90: 575–581.
   PubMed Web of Science ®Google Scholar
• Ieiri I, Nishimura C, Maeda K, et al. Pharmacokinetic and pharmacogenomic profiles of telmisartan after the oral microdose and therapeutic dose. Pharmacogenet Genomics 2011; 21: 495–505.
   PubMed Web of Science ®Google Scholar
• Sevick-Muraca EM, Sharma R, Rasmussen JC, et al. Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study. Radiology 2008; 246: 734–741.
   PubMed Web of Science ®Google Scholar
• Pan CX, Wang S, De Vere White R, et al. A Phase 0 microdosing clinical trial to identify chemoresistance. Cancer Res 2011; 71(Suppl. 1): LB-403.
   Google Scholar
• M. D. Anderson Cancer Center. Temsirolimus In Phase 0. In: ClinicalTrials.gov [Internet]. Bethesda, MD: National Library of Medicine; 2000. Available from: http://clinicaltrials.gov/show/NCT01417065 NLM Identifier: NCT01417065. Accessed August 4, 2014.
   Google Scholar
• University of California, Davis. A diagnostic Feasibility Trial of a [14C]Oxaliplatin Microdosing Assay for Prediction of Chemoresistance to Oxaliplatin Chemotherapy. In: ClinicalTrials.gov [Internet]. Bethesda, MD: National Library of Medicine; 2000. Available from: http://clinicaltrials.gov/show/NCT02077998 NLM Identifier: NCT02077998. Accessed August 5, 2014.
   Google Scholar
• Lappin G, Kuhnz W, Jochemsen R, et al. Use of microdosing to predict pharmacokinetics at the therapeutic dose: Experience with 5 drugs. Clin Pharmacol Ther 2006; 80: 203–215.
   PubMed Web of Science ®Google Scholar
• Lappin G, Noveck R, Burt T. Microdosing and drug development: past, present and future. Expert Opin Drug Metab Toxicol 2013; 9: 817–834.
   PubMed Web of Science ®Google Scholar
• Boulton DW, Kasichayanula S, Keung CF, et al. Simultaneous oral therapeutic and intravenous 14C-microdoses to determine the absolute oral bioavailability of saxagliptin and dapagliflozin. Br J Clin Pharmacol 2013; 75: 763–768.
   PubMed Web of Science ®Google Scholar
• Jiang H, Zeng J, Li W, et al. Practical and efficient strategy for evaluating oral absolute bioavailability with an intravenous microdose of a stable isotopically-labeled drug using a selected reaction monitoring mass spectrometry assay. Anal Chem 2012; 84: 10031–10037.
   PubMed Web of Science ®Google Scholar
• Xu XS, Dueker SR, Christopher LJ, et al. Overcoming bioanalytical challenges in an Onglyza intravenous [(14)C]microdose absolute bioavailability study with accelerator MS. Bioanalysis 2012; 4: 1855–1870.
   PubMed Web of Science ®Google Scholar
• Vuong LT, Blood AB, Vogel JS, et al. Applications of accelerator MS in pediatric drug evaluation. Bioanalysis 2012; 4: 1871–1882.
   PubMed Web of Science ®Google Scholar
• Henderson PT, Li T, He M, et al. A microdosing approach for characterizing formation and repair of carboplatin-DNA monoadducts and chemoresistance. Int J Cancer 2011; 129: 1425–1434.
   PubMed Web of Science ®Google Scholar
• Kinders R, Parchment RE, Ji J, et al. Phase 0 clinical trials in cancer drug development: From FDA guidance to clinical practice. Mol Interv 2007; 7: 325–334.
   PubMed Web of Science ®Google Scholar
• Kummar S, Rubinstein L, Kinders R, et al. Phase 0 clinical trials: conceptions and misconceptions. Cancer J 2008; 14: 133–137.
   PubMed Web of Science ®Google Scholar
• Takimoto CH. Phase 0 clinical trials in oncology: a paradigm shift for early drug development? Cancer Chemother Pharmacol 2009; 63: 703–709.
   PubMed Web of Science ®Google Scholar
• Ieiri I, Fukae M, Maeda K, et al. Pharmacogenomic/pharmacokinetic assessment of a four–probe cocktail for CYPs and OATPs following oral microdosing. Int J Clin Pharmacol Ther 2012; 50: 689–700.
   PubMed Web of Science ®Google Scholar
• Yamane N, Takami T, Tozuka Z, et al. Microdose clinical trial: quantitative determination of nicardipine and prediction of metabolites in human plasma. Drug Metab Pharmacokinet 2009; 24: 389–403.
   PubMed Web of Science ®Google Scholar