Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
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Biomarkers (BM) are gradually being recognized as useful tools to evaluate drugs from development through post-approval periods. In the past decade, practical use of BM has advanced particularly in the field of anti-cancer drug development. Regardless of the use of BM, approximately 10% of key clinical trials for new drug applications of anti-cancer drugs were conducted as multiregional clinical trials. ⋯ However, only two guidelines regarding BM, i.e., terminologies of pharmacogenomics (E15 guideline) and document format in BM qualification submission to regulatory agencies (E16 guideline), have been harmonized in the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) so far. It is important to strengthen international harmonization and collaboration among academia, industry, and regulatory agencies, followed by the establishment of an international guideline on the application of BM in drug evaluation. This article outlines the regulatory perspective on remaining challenges and current Pharmaceuticals and Medical Devices Agency (PMDA) activities for use of BM in drug evaluation.
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Use of prescription opioids for cancer pain according to the World Health Organization analgesic ladder has been accepted in Japan. Although oxycodone and fentanyl are commonly used as first-line analgesics, a few clinical reports have been published on interindividual variations in their pharmacokinetics and clinical responses in cancer patients. (1) Some factors relating to CYP2D6, CYP3A, ATP-binding cassette sub-family B member 1 (ABCB1), and opioid receptor mu 1 (OPRM1) involve oxycodone pharmacokinetics and sensitivity in humans. The relations between their genetic variations and clinical responses to oxycodone are being revealed in limited groups. ⋯ However, the variations in opioid switching remain to be clarified in clinical settings. In our study, genetic factors related to interindividual variations in clinical responses in opioid switching to fentanyl were revealed in Japanese populations. In this symposium review, the possibility of approaches to personalized palliative care using opioids based on genetic variants of CYP2D6, CYP3A5, ABCB1, and OPRM1 is discussed.