Pemafibrate, một tác nhân điều biến PPARα chọn lọc mới: Khái niệm thuốc và các ứng dụng lâm sàng của nó cho rối loạn lipid máu và bệnh chuyển hóa

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Cardiovasc Diabetol. 2017;16:124 This is a very nice review on the development of a novel SPPARMα, pemafibrate, and its clinical efficacy. Shelly W, Draper MW, Krishnan V, Wong M, Jaffe RB. Selective estrogen receptor modulators: an update on recent clinical findings. Obstet Gynecol Surv. 2008;63(3):163–81. Yamazaki Y, Abe K, Toma T, Nishikawa M, Ozawa H, Okuda A, et al. Design and synthesis of highly potent and selective human peroxisome proliferator-activated receptor alpha agonists. Bioorg Med Chem Lett. 2007;17(16):4689–93. •• Yamamoto Y, Takei K, Arulmozhiraja S, Sladek V, Matsuo N, Han SI, et al. Molecular association model of PPARalpha and its new specific and efficient ligand, pemafibrate: Structural basis for SPPARMalpha. Biochem Biophys Res Commun. 2018;499(2):239–45 This paper computationally constructed the structure of human PPARα in a complex with pemafibrate in comparison with fenofibrate. 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J Clin Lipidol. 2018;12(5):1267–79 This study showed that pemafibrate increases small sized HDL particles with more potent cholesterol efflux capacity than those treated with placebo. •• Araki E, Yamashita S, Arai H, Yokote K, Satoh J, Inoguchi T, et al. Effects of pemafibrate, a novel selective PPARalpha 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. 2018;41(3):538–46 In this study, pemafibrate was administered for 24 weeks in hypertriglyceridemic patients with type 2 diabetes. Fasting blood glucose and insulin levels and HOMA-IR were significantly reduced by pemafibrate in comparison with placebo. Okazaki M, Yamashita S. Recent advances in analytical methods on lipoprotein subclasses: calculation of particle numbers from lipid levels by gel permeation HPLC using "spherical particle model". J Oleo Sci. 2016;65(4):265–82. 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Fibroblast growth factor 21 enhances cholesterol efflux in THP-1 macrophage-derived foam cells. Mol Med Rep. 2015;11(1):503–8. Hounslow N, Suganami H, Nakamura M. Pemafibrate minimally affected the systemic exposure of statins, and vice versa, in healthy male volunteers. Atherosclerosis Supplements. 2018;32:156–7 [ISA2018 Abstract]. • Arai H, Yamashita S, Yokote K, Araki E, Suganami H, Ishibashi S. Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor alpha modulator (SPPARMalpha), in combination with statin treatment: two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia. Atherosclerosis. 2017;261:144–52 This paper evaluated the efficacy and safety of pemafibrate add-on therapy during statin treatment. • Arai H, Yamashita S, Yokote K, Araki E, Suganami H, Ishibashi S. 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. 2018;25(6):521–38 This paper reports the results of a placebo-controlled, double-blind trial which evaluated the efficacy and safety of pemafibrate versus fenofibrate in patients with high triglyceride and low HDL-C levels. • Ishibashi S, Arai H, Yokote K, Araki E, Suganami H, Yamashita S. Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator-activated receptor alpha modulator, in patients with dyslipidemia: Results from a 24-week, randomized, double blind, active-controlled, phase 3 trial. J Clin Lipidol. 2018;12(1):173–84 This paper compared the efficacy and safety of pemafibrate and fenofibrate. Pemafibrate was superior to fenofibrate in terms of serum TG-lowering effect and hepatic and renal safety. 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A pooled analysis of pemafibrate phase II/III clinical trials indicated significant improvement in glycemic and liver function-related parameters. Atherosclerosis Supplements. 2018;32:154–5 [ISA2018 Abstract]. • Takei K, Han SI, Murayama Y, Satoh A, Oikawa F, Ohno H, et al. Selective peroxisome proliferator-activated receptor-alpha modulator K-877 efficiently activates the peroxisome proliferator-activated receptor-alpha pathway and improves lipid metabolism in mice. J Diabetes Investig. 2017;8(4):446–52 This paper investigated the effects of pemafibrate and fenofibrate on the pathology of MCD diet-induced non-alcoholic fatty liver disease, suggesting a favorable effect of pemafibrate on NAFLD/NASH. • Honda Y, Kessoku T, Ogawa Y, Tomeno W, Imajo K, Fujita K, et al. Pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, improves the pathogenesis in a rodent model of nonalcoholic steatohepatitis. 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