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Warner A.W.,Merck And Co. | Bienfait K.L.,Merck And Co. | Bledsoe M.,Office of Research and Development | Burckart G.,Office of Clinical Pharmacology | And 7 more authors.
Pharmacogenomics | Year: 2013

Clinical trial samples collected for pharmacogenomic and future research are vital resources for the development of safe and effective drugs, yet collecting adequate, representative sample sets in global trials is challenging. The Drug Information Association (DIA) sponsored a workshop on future use sampling in September 2011, bringing together experts from regulatory agencies, academia and industry to discuss challenges to future use sample collection and identify actions to improve collection. Several common themes and associated action items emerged, including the need for international guidance on the collection of samples for future research; additional discussion related to coding, scope of research, and return of research results; and additional education about pharmacogenomic/future research and the importance of long-term storage of specimens. © 2013 Future Medicine Ltd. Source


Katayama R.,Massachusetts General Hospital | Katayama R.,Harvard University | Aoyama A.,Divisions of Experimental Chemotherapy | Aoyama A.,Tokyo Medical University | And 8 more authors.
Cancer Research | Year: 2013

The receptor tyrosine kinase c-MET is the high-affinity receptor for the hepatocyte growth factor (HGF). The HGF/c-MET axis is often dysregulated in tumors. c-MET activation can be caused by MET gene amplification, activating mutations, and auto- or paracrine mechanisms. Thus, c-MET inhibitors are under development as anticancer drugs. Tivantinib (ARQ 197) was reported as a small-molecule c-MET inhibitor and early clinical studies suggest antitumor activity. To assess whether the antitumor activity of tivantinib was due to inhibition of c-MET, we compared the activity of tivantinib with other c-MET inhibitors in both c-MET-addicted and nonaddicted cancer cells. As expected, other c-MET inhibitors, crizotinib and PHA-665752, suppressed the growth of c-MET-addicted cancers, but not the growth of cancers that are not addicted to c-MET. In contrast, tivantinib inhibited cell viability with similar potency in both c-MET-addicted and nonaddicted cells. These results suggest that tivantinib exhibits its antitumor activity in a manner independent of c-MET status. Tivantinib treatment induced a G2-M cell-cycle arrest in EBC1 cells similarly to vincristine treatment, whereas PHA-665752 or crizotinib treatment markedly induced G0-G1 cell-cycle arrest. To identify the additional molecular target of tivantinib, we conducted COMPARE analysis, an in silico screening of a database of drug sensitivities across 39 cancer cell lines (JFCR39), and identified microtubule as a target of tivantinib. Tivantinib-treated cells showed typical microtubule disruption similar to vincristine and inhibited microtubule assembly in vitro. These results suggest that tivantinib inhibits microtubule polymerization in addition to inhibiting c-MET. Cancer Res; 73(10); 3087-96. © 2013 AACR. Source


Nagai N.,Pharmaceuticals and Medical Devices Agency PMDA
Drug Metabolism and Pharmacokinetics | Year: 2010

Drug interaction studies on new drug applications (NDAs) for new molecular entities (NMEs) approved in Japan between 1997 and 2008 are examined in the Pharmaceuticals and Medical Devices Agency (PMDA). The situations of drug interaction studies in NDAs have changed over the past 12 years, especially in metabolizing enzyme and transporter-based drug interactions. Materials and approaches to study drugmetabolizing enzyme-based drug interactions have improved, and become more rational based on mechanistic theory and new technologies. On the basis of incremental evidence of transporter roles in human pharmacokinetics, transporter-based drug interactions have been increasingly studied during drug development and submitted in recent NDAs. Some recently approved NMEs include transporter-based drug interaction information in their package inserts (PIs). The regulatory document "Methods of Drug Interaction Studies," in addition to recent advances in science and technology, has also contributed to plan and evaluation of drug interaction studies in recent new drug development. This review summarizes current situations and further discussion points on drug interaction studies in NDAs in Japan. Source


Ishikawa H.,Pharmaceuticals and Medical Devices Agency PMDA
Transactions of Japanese Society for Medical and Biological Engineering | Year: 2014

Introduction and consultation about quality and safety view from the initial stage of the development in order to create innovative medical devices. This consultation system is mainly for University, Laboratories and venture companies who has very progressive idea or studies but the little experience bout the regulation. © 2014, Japan Soc. of Med. Electronics and Biol. Engineering. All rights reserved. Source


Otsubo Y.,Pharmaceuticals and Medical Devices Agency PMDA | Asahina Y.,Pharmaceuticals and Medical Devices Agency PMDA | Noguchi A.,Pharmaceuticals and Medical Devices Agency PMDA | Sato Y.,Pharmaceuticals and Medical Devices Agency PMDA | And 4 more authors.
Drug Metabolism and Pharmacokinetics | Year: 2012

Summary: Pharmacogenomics (PGx) has been utilized as a tool to improve a drug's benefit/risk ratio and the efficiency of drug developments. In order to examine what factors are involved to determine the level of contexts (contents and descriptions) of drug-PGx biomarker information, we graded sections of Japanese package inserts and US drug labels into six levels according to the importance of cautions in regards to clinical practice and compared similarities and differences of the contexts between the two countries. Out of 54 contexts identified, 33 (61%) were graded differently between Japan and the US. The different contexts were mainly related to metabolizing enzymes used in terms of safety, therapeutic areas other than oncology, outcome before 1993, Japan-based companies having marketing authorization and no PGx data on the Japanese population. We describe the potential reasons that could lead to the differences between the two countries such as genetic differences and quantitative evidence in the Japanese population, and also discuss future perspectives to improve PGx utilization in clinical practices in Japan. © 2012 by the Japanese Society for the Study of Xenobiotics (JSSX). Source

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