5. Microdose Clinical Study for Drug Development

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  • MAEDA Kazuya
    Department of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo
  • SUGIYAMA Yuichi
    Department of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo

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  • ５．開発戦略におけるマイクロドーズ臨床試験

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Though many types of in vitro high-throughput screening systems have been developed, the number of new drug applications has not increased. One of the reasons is that the time profiles of plasma and tissue concentrations in humans are not desirable for pharmacological actions. Thus, the pharmacokinetics of drug candidates in humans are needed in order to select the most appropriate drugs for further clinical development. The microdosing (MD) study is a powerful approach to directly obtain pharmacokinetic data in humans without extensive toxicology studies. This approach can yield quantitative profiling of drug metabolites by accelerator mass spectrometer (AMS), comparison of plasma and urine profiles of drug candidates simultaneously by cocktail MD administration and measurement by high-spec LC/MS/MS, and real-time monitoring of tissue concentration by positron emission tomography (PET). Therefore, human MD study prior to a clinical study should be very helpful for theoretical drug selection. On the other hand, the concern about the linearity of pharmacokinetics between administration of MD and therapeutic dose is often an issue. In this article, we discuss how to obtain the human pharmacokinetic data of drug candidates by MD study and predict the pharmacokinetics of the clinical dose of specific drugs based on the results of MD and in vitro studies.

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