SPPARMαへの期待

出版社： フジメディカル出版
著者：
発行日： 2019-06-10
分野： 臨床医学：内科  >  循環器一般
ISBN： 9784862701725
電子書籍版： 2019-06-10 （初版第1刷）
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商品紹介

選択的PPARαモジュレータ―（SPPARMα）という新たな概念に基づいて創薬されたペマフィブラート。フィブラートを超えた新たなPPARαアゴニストとしての期待は大きい。
その開発の経緯，遺伝子発現解析，作用機序，適応疾患（高TG血症・低HDL-C血症）と使い方，スタチンとの併用療法，安全性（副作用，相互作用）など，新薬の特性を国内屈指の執筆順が詳解。
「脂質異常症」の診療に携わる臨床医必備の1冊。

目次

  • 1 SPPARMαとは？
    　1）パルモディア®はいかに開発されたか：PPAR薬の革新への2つのイノベーション
    　2）遺伝子発現解析からみた有用性
    　3）作用メカニズム ―構造の特徴から作用特性まで
    　4）世界におけるSPPARMα開発の最先端

    2 SPPARMαの臨床
    　1）高TG血症に対して（高レムナント血症，small dense LDLも含めて）
    　2）低HDL-C血症に対して
    　3）スタチンとの併用
    　4）動脈硬化性疾患予防におけるポジショニング

    3 SPPARMαの安全性
    　1）副作用
    　2）薬物動態と薬物相互作用

    4 SPPARMαの幅広い使い方
    　1）腎機能低下例
    　2）NASH
    　3）肥満・メタボリックシンドローム
    　4）２型糖尿病合併例
    　5）高齢者

    5 SPPARMαのエビデンス
    　1）フィブラートのRCTの歴史
    　2）PROMINENTの意義・概要

    6 トピックス
    　topic 1）冠動脈疾患発症における中性脂肪の関わり
    　topic 2）食後高中性脂肪血症管理の重要性
    　topic 3）遺伝子多型から考えるトリグリセライドリスク
    　topic 4）血管炎症におけるPPARαの関わり
    　　　　　　　SPPARMαによる血管慢性炎症抑制のメカニズムと効果への期待
    　topic 5）褐色脂肪細胞およびベージュ脂肪細胞の分化・機能制御におけるPPARαの関わり

    7 SPPARMαの展望　－まとめに代えて

この書籍の参考文献

参考文献のリンクは、リンク先の都合等により正しく表示されない場合がありますので、あらかじめご了承下さい。

本参考文献は電子書籍掲載内容を元にしております。

イントロダクション

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1 SPPARMαとは ?

P.40 掲載の参考文献
1) Issemann I, Green S : Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347 : 645-650, 1990
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12) Araki E et al : Effects of Pemafibrate, a Novel Selective PPARα Modulator, on Lipid and Glucose Metabolism in Patients With Type 2 Diabetes and Hypertriglyceridemia : A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial. Diabetes Care 41 : 538-546, 2018
 
13) Ishibashi S et al ; K-877 Study Group : Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator-activated receptor α modulator, in patients with dyslipidemia : Results from a 24-week, randomized, double blind, active-controlled, phase 3 trial. J Clin Lipidol 12 : 173-184, 2018
 
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P.49 掲載の参考文献
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3) Fruchart JC : Selective peroxisome proliferator-activated receptor α modulators (SPPARMα) : the next generation of peroxisome proliferator-activated receptor α-agonists. Cardiovasc Diabetol 12 : 82, 2013
 
4) Raza-Iqbal S et al : Transcriptome Analysis of K-877 (a Novel Selective PPARα Modulator (SPPARMα)) -Regulated Genes in Primary Human Hepatocytes and the Mouse Liver. J Atheroscler Thromb 22 : 754-772, 2015
 
5) Ishibashi S et al, K-877-04 Study Group : Effects of K-877, a novel selective PPARα modulator (SPPARMα), in dyslipidaemic patients : A randomized, double blind, activeand placebo-controlled, phase 2 trial. Atherosclerosis 249 : 36-43, 2016
 
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P.60 掲載の参考文献
1) Fruchart JC : Selective peroxisome proliferator-activated receptor α modulators (SPPARMα) : the next generation of peroxisome proliferator-activated receptor α-agonists. Cardiovasc Diabetol 12 : 82, 2013
 
2) Takei K et al : Selective peroxisome proliferator-activated receptor-α modulator K-877 efficiently activates the peroxisome proliferator-activated receptor-α pathway and improves lipid metabolism in mice. J Diabetes Investig 8 : 446-452, 2017
 
3) Raza-Iqbal S et al : Transcriptome Analysis of K-877 (a Novel Selective PPARα Modulator (SPPARMα)) -Regulated Genes in Primary Human Hepatocytes and the Mouse Liver. J Atheroscler Thromb 22 : 754-772, 2015
 
4) Takei K et al : Effects of K-877, a novel selective PPARα modulator, on small intestine contribute to the amelioration of hyperlipidemia in low-density lipoprotein receptor knockout mice. J Pharmacol Sci 133 : 214-222, 2017
 
5) Araki M et al : The Peroxisome Proliferator-Activated Receptor α (PPARα) Agonist Pemafibrate Protects against Diet-Induced Obesity in Mice. Int J Mol Sci 19 : 2148, 2018
 
6) Yamamoto Y et al : Molecular association model of PPARα and its new specific and efficient ligand, pemafibrate : Structural basis for SPPARMα. Biochem Biophys Res Commun 499 : 239-245, 2018
 
P.63 掲載の参考文献
1) Yamazaki Y et al : Design and synthesis of highly potent and selective human peroxisome proliferator-activated receptor alpha agonists. Bioorg Med Chem Lett 17 : 4689-4693, 2007
PubMed
2) Yamamoto Y et al : Molecular association model of PPARα and its new specific and efficient ligand, pemafibrate : Structural basis for SPPARMα. Biochem Biophys Res Commun 499 : 239-245, 2018
 
3) Raza-Iqbal S et al : Transcriptome Analysis of K-877 (a Novel Selective PPARα Modulator (SPPARMα)) -Regulated Genes in Primary Human Hepatocytes and the Mouse Liver. J Atheroscler Thromb 22 : 754-772, 2015
 
4) Hennuyer N et al : The novel selective PPARα modulator (SPPARMα) pemafibrate improves dyslipidemia, enhances reverse cholesterol transport and decreases inflammation and atherosclerosis. Atherosclerosis 249 : 200-208, 2016
 
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6) Ishibashi S et al : Effects of K-877, a novel selective PPARα modulator (SPPARMα), in dyslipidaemic patients : A randomized, double blind, active- and placebo-controlled, phase 2 trial. Atherosclerosis 249 : 36-43, 2016
 
7) Ishibashi S et al : Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator-activated receptor α modulator, in patients with dyslipidemia : Results from a 24-week, randomized, double blind, active-controlled, phase 3 trial. J Clin Lipidol 12 : 173-184, 2018
 
8) Arai H et al : Efficacy and Safety of Pemafibrate Versus Fenofibrate in Patients with High Triglyceride and Low HDL Cholesterol Levels : A Multicenter, Placebo-Controlled, Double-Blind, Randomized Trial. J Atheroscler Thromb 25 : 521-538, 2018
 
9) Matsuba I et al : Effects of a novel selective peroxisome proliferator-activated receptor-α modulator, pemafibrate, on hepatic and peripheral glucose uptake in patients with hypertriglyceridemia and insulin resistance. J Diabetes Investig 9 : 1323-1332, 2018
 
10) Araki E et al : Effects of Pemafibrate, a Novel Selective PPARα Modulator, on Lipid and Glucose Metabolism in Patients With Type 2 Diabetes and Hypertriglyceridemia : A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial. Diabetes Care 41 : 538-546, 2018
 
11) Arai H et al : Efficacy and safety of K-877, a novel selective peroxisome proliferatoractivated receptor α modulator (SPPARMα), in combination with statin treatment : Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia. Atherosclerosis 261 : 144-152, 2017
 
12) Yamashita S et al : Effects of pemafibrate (K-877) on cholesterol efflux capacity and postprandial hyperlipidemia in patients with atherogenic dyslipidemia. J Clin Lipidol 12 : 267-1279.e4, 2018
 

2 SPPARMαの臨床

P.75 掲載の参考文献
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P.84 掲載の参考文献
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10) Hennuyer N et al : The novel selective PPARα modulator (SPPARMα) pemafibrate improves dyslipidemia, enhances reverse cholesterol transport and decreases inflammation and atherosclerosis. Atherosclerosis 249 : 200-208, 2016
 
11) Raza-Iqbal S et al : Transcriptome Analysis of K-877 (a Novel Selective PPARα Modulator (SPPARMα)) -Regulated Genes in Primary Human Hepatocytes and the Mouse Liver. J Atheroscler Thromb 22 : 754-772, 2015
 
12) Ishibashi S et al : Effects of K-877, a novel selective PPARα modulator (SPPARMα), in dyslipidaemic patients : A randomized, double blind, active- and placebo-controlled, phase 2 trial. Atherosclerosis 249 : 36-43, 2016
 
13) Ishibashi S et al ; K-877 Study Group : Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator-activated receptor αmodulator, in patients with dyslipidemia : Results from a 24-week, randomized, double blind, active-controlled, phase 3 trial. J Clin Lipidol 12 : 173-184, 2018
 
14) Arai H et al ; K-877 Study Group : Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment : Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia. Atherosclerosis 261 : 144-152, 2017
 
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2) ACCORD Study Group, Ginsberg HN et al : Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 362 : 1563-1574, 2010
 
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3 SPPARMαの安全性

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2) ACCORD Study Group, Ginsberg HN et al : Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 362 : 1563-1574, 2010
 
3) パルモディア錠インタビューフォーム
 
4) Ishibashi S et al : Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator-activated receptor α modulator, in patients with dyslipidemia : Results from a 24-week, randomized, double blind, active-controlled, phase 3 trial. J Clin Lipidol 12 : 173-184, 2018
 
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4 SPPARMαの幅広い使い方

P.126 掲載の参考文献
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4) Araki E et al : Effects of Pemafibrate, a Novel Selective PPARα Modulator, on Lipid and Glucose Metabolism in Patients With Type 2 Diabetes and Hypertriglyceridemia : A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial. Diabetes Care 41 : 538-546, 2018
 
5) 医薬品インタビューフォーム 高脂血症治療剤パルモディア錠
 
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10) Maki T et al : Renoprotective effect of a novel selective PPARα modulator K-877 in db/db mice : A role of diacylglycerol-protein kinase C-NAD (P) H oxidase pathway. Metabolism 71 : 33-45, 2017
 
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5 SPPARMαのエビデンス

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6 トピックス

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7 SPPARMαの展望 - まとめに代えて

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