Japan Pharmaceutical Information Center

Shibuya-ku, Japan

Japan Pharmaceutical Information Center

Shibuya-ku, Japan
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Tsuji M.,Institute of Molecular Function | Shudo K.,Japan Pharmaceutical Information Center | Kagechika H.,Tokyo Medical and Dental University
FEBS Open Bio | Year: 2017

Understanding and identifying the receptor subtype selectivity of a ligand is an important issue in the field of drug discovery. Using a combination of classical molecular mechanics and quantum mechanical calculations, this report assesses the receptor subtype selectivity for the human retinoid X receptor (hRXR) and retinoic acid receptor (hRAR) ligand-binding domains (LBDs) complexed with retinoid ligands. The calculated energies show good correlation with the experimentally reported binding affinities. The technique proposed here is a promising method as it reveals the origin of the receptor subtype selectivity of selective ligands. © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.


Oshima Y.,Tokyo Medical University | Oshima Y.,Cancer Institute | Yuji K.,Tokyo Medical University | Tanimoto T.,Cancer Institute | And 3 more authors.
Internal Medicine | Year: 2013

Objective The development of myeloid malignancies is a concern when administering thrombopoietin receptor (or the myeloproliferative leukemia virus proto-oncogene product, MPL) agonists. Progression from myelodysplastic syndrome (MDS) to acute myelogenous leukemia [AML, 9 (6.12%) AML patients among 147 MDS subjects] was reported in a clinical trial. However, only one (0.15%) case of AML among 653 immune thrombocytopenic purpura (ITP) subjects was reported. Our objective was to determine whether there is currently a safety signal in the FDA files termed Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) for AML in ITP patients who receive MPL agonists. Methods We conducted a case-controlled study using the FAERS as a source of case and control data. We compared demographic characteristics, such as gender, age and exposure to MPL agonists between AML patients and others among ITP subjects registered between 2002 and 2011. Results Total of 4,821 ITP subjects were identified, including 62 AML patients. The number of patients treated with romiplostim and eltrombopag was 54 (1.74%) AML patients among 3,102 ITP subjects and nine (1.52%) AML patients among 594 ITP subjects, respectively. It should be noted that all AML patients were exposed to one or more MPL agonists. Another factor associated with AML was male gender. Conclusion We herein report an association between AML and MPL agonist use in ITP subjects. Due to various biases and the incompleteness of the FAERS data, further studies are warranted to determine whether the detected signal is a real risk. Physicians should not alter their prescribing behaviors based on this single preliminary analysis. © 2013 The Japanese Society of Internal Medicine.


Hashiguchi M.,Keio University | Imai S.,Keio University | Uehara K.,Japan Pharmaceutical Information Center | Maruyama J.,Keio University | And 2 more authors.
PLoS ONE | Year: 2015

We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2-10 months for known ADRs and 19-44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0-122.5 days and 185.5-306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release. © 2015 Hashiguchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Arai Y.,Japan Pharmaceutical Information Center
Yakushigaku zasshi. The Journal of Japanese history of pharmacy | Year: 2010

There are approximately 1300 kinds of ethical drugs currently approved for use in Japan, excluding high molecular weight drugs and Chinese medicines. Among them, 81 contain alpha-amino acids, though some consist of a-amino acid parenteral fluid and peptide-type drugs, which include ACE inhibitors. Of these, 30 kinds of drugs are made from both natural and non-natural amino acids, and 51 kinds of drugs are prepared from amino acid derivatives. All of these drugs were developed in the last 50 years. Amino acids moieties such as D-phenylglycine and D-phydroxyphenylglycine have contributed to enhancing the stability, absorbability, and effectiveness of many drugs, particularly antibiotics, such as certain types of penicillin and cephalosporin. In recent years, radioactive and antiviral agents containing amino acid skeletons have also been developed for use as anti-AIDS medications.


Tsuji M.,Institute of Molecular Function | Shudo K.,Japan Pharmaceutical Information Center | Kagechika H.,Tokyo Medical and Dental University
Journal of Computer-Aided Molecular Design | Year: 2015

Retinoid X receptors (RXRs) are ligand-controlled transcription factors which heterodimerize with other nuclear receptors to regulate gene transcriptions associated with crucial biological events. 9-cis retinoic acid (9cRA), which transactivates RXRs, is believed to be an endogenous RXR ligand. All-trans retinoic acid (ATRA) is a natural ligand for retinoic acid receptors (RARs), which heterodimerize with RXRs. Although the concentration of 9cRA in tissues is very low, ATRA is relatively abundant and some reports show that ATRA activates RXRs. We computationally studied the possibility of ATRA binding to RXRs using two different docking methods with our developed programs to assess the binding affinities of naturally occurring retinoids. The simulations showed good correlations to the reported binding affinities of these molecules for RXRs and RARs. © 2015 Springer International Publishing Switzerland


Takahashi H.,Japan Pharmaceutical Information Center
Yakushigaku zasshi. The Journal of Japanese history of pharmacy | Year: 2010

The drug reevaluation system was established to review the quality, efficacy and safety of drugs approved in the past based on current medical and pharmaceutical scientific standards. There have been three reevaluations of ethical drugs in Japan implemented according to the approved dates. The first reevaluation started in 1971 and finished in 1995 for the drugs that were approved up until September 1967. The second reevaluation started in 1984 and finished in 1996 for the drugs that were approved between October 1967 and March 1980. The new reevaluation system for all drugs regardless of the approval date consists of periodic reevaluation and Ad Hoc reevaluation. This system started in 1988 and has continued up to the present. Periodic reevaluation is a system where the efficacy and safety of drugs of all therapeutic categories are reviewed every five years based on literature screening. However, this system is currently suspended. Ad Hoc reevaluation is used to supplement periodic reevaluation and is performed at the onset of an emergency or when an entire therapeutic category becomes roblematic. In the second reevaluation and new reevaluation system, it is harder to judge which products must be reevaluated than in the first reevaluation for all drugs. In addition, the quality reevaluation for oral solid formulations based on dissolution studies started in February in 1997 and is almost finished.


PubMed | Institute of Molecular Function, Japan Pharmaceutical Information Center and Tokyo Medical and Dental University
Type: Journal Article | Journal: Journal of computer-aided molecular design | Year: 2015

Retinoid X receptors (RXRs) are ligand-controlled transcription factors which heterodimerize with other nuclear receptors to regulate gene transcriptions associated with crucial biological events. 9-cis retinoic acid (9cRA), which transactivates RXRs, is believed to be an endogenous RXR ligand. All-trans retinoic acid (ATRA) is a natural ligand for retinoic acid receptors (RARs), which heterodimerize with RXRs. Although the concentration of 9cRA in tissues is very low, ATRA is relatively abundant and some reports show that ATRA activates RXRs. We computationally studied the possibility of ATRA binding to RXRs using two different docking methods with our developed programs to assess the binding affinities of naturally occurring retinoids. The simulations showed good correlations to the reported binding affinities of these molecules for RXRs and RARs.


PubMed | Japan Pharmaceutical Information Center and Keio University
Type: Journal Article | Journal: PloS one | Year: 2015

We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2-10 months for known ADRs and 19-44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0-122.5 days and 185.5-306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release.


PubMed | Kissei Pharmaceutical Co Ltd, Daiichi Sankyo, Jikei University School of Medicine, Keio University and 2 more.
Type: | Journal: Drug design, development and therapy | Year: 2015

The use of a statistical approach to analyze cumulative adverse event (AE) reports has been encouraged by regulatory authorities. However, data variations affect statistical analyses (eg, signal detection). Further, differences in regulations, social issues, and health care systems can cause variations in AE data. The present study examined similarities and differences between two publicly available databases, ie, the Japanese Adverse Drug Event Report (JADER) database and the US Food and Drug Administration Adverse Event Reporting System (FAERS), and how they affect signal detection.Two AE data sources from 2010 were examined, ie, JADER cases (JP) and Japanese cases extracted from the FAERS (FAERS-JP). Three methods for signals of disproportionate reporting, ie, the reporting odds ratio, Bayesian confidence propagation neural network, and Gamma Poisson Shrinker (GPS), were used on drug-event combinations for three substances frequently recorded in both systems.The two databases showed similar elements of AE reports, but no option was provided for a shareable case identifier. The average number of AEs per case was 1.61.3 (maximum 37) in the JP and 3.33.5 (maximum 62) in the FAERS-JP. Between 5% and 57% of all AEs were signaled by three quantitative methods for etanercept, infliximab, and paroxetine. Signals identified by GPS for the JP and FAERS-JP, as referenced by Japanese labeling, showed higher positive sensitivity than was expected.The FAERS-JP was different from the JADER. Signals derived from both datasets identified different results, but shared certain signals. Discrepancies in type of AEs, drugs reported, and average number of AEs per case were potential contributing factors. This study will help those concerned with pharmacovigilance better understand the use and pitfalls of using spontaneous AE data.


PubMed | Zhejiang University, Japan Pharmaceutical Information Center, University of Southern California and Saban Research Institute
Type: Journal Article | Journal: EMBO molecular medicine | Year: 2016

Neutrophils generated by granulocyte colony-stimulating factor (GCSF) are functionally immature and, consequently, cannot effectively reduce infection and infection-related mortality in cancer chemotherapy-induced neutropenia (CCIN). Am80, a retinoic acid (RA) agonist that enhances granulocytic differentiation by selectively activating transcription factor RA receptor alpha (RAR), alternatively promotes RA-target gene expression. We found that in normal and malignant primary human hematopoietic specimens, Am80-GCSF combination coordinated proliferation with differentiation to develop complement receptor-3 (CR3)-dependent neutrophil innate immunity, through altering transcription of RA-target genes RAR

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