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Microdose clinical trials can be utilized for the purpose to gain pharmacokinetic information on a tentative drug candidate in human using labelled compound(s) and AMS or imaging technology using PET, or non-labelled compound(s) and LC/MS/MS, and to select drug candidate by ensuring adequate properties in early stage. In 2008, the NEDO (New Energy and Industrial Technology Development Organization) project entitled ‘Establishment of Evolutional Drug development with the Use of Microdosing Clinical Trial’ was adopted. In this project, the quantitative prediction method on drug absorption, distribution, metabolism and excretion (ADME) using modeling and simulation will be applied to human to validate this methodology. That is, based on the in vitro data on metabolism, transport and binding with animal and human tissues, the drug concentration–time profiles in the plasma and target tissues such as the brain, tumor, liver and kidney will be predicted and the validity of the predictions will be investigated by using clinical studies under its microdose and therapeutic dose conditions. PET is a promising approach to determine the functional change of transporters associated with genetic polymorphisms or drug–drug interactions. Labeled PET probes have been developed for specific transporters in this NEDO project. In addition, in 2010, the Ministry of Education, Culture, Sports, Science and Technology (MEXT) has launched its second program, the ‘J-AMP; Japan Advanced Molecular Imaging Program’, using the two major centers (RIKEN, NIRS). In this project, research is undertaken focusing on the cancer and dementia fields to contribute to the development of new drugs and biomarkers as diagnostic tools.

Here, in this presentation, I will share with you our recent progress in the use of the analysis of plasma clearance of drugs and PET imaging to evaluate the transporter function in vivo.


1. Giacomini KM, Sugiyama Y. Membrane transporters and drug response. In Brunton LL, Chabner BA, Knollman B (eds) Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12th edition, Chapter 5. New York, NY: McGraw-Hill 2011; 89–122.

2) Sugiyama Y. Effective use of microdosing and positron emission tomography (PET) studies on new drug discovery and development. Drug Metab Pharmacokinet 2009; 24: 127–129.

3) Sugiyama Y, Yamashita S. Impact of microdosing Clinical Study—why necessary and how useful? Adv Drug Deliv Rev 2011; 63: 494–502.

Takashima T, Nagata H, Nakae T, et al. PET studies using 15R-[11C]TIC-Me for the evaluation of hepatobiliary transport. J Pharmacol Exp Ther 2010; 335: 314–323.

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