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薬理と治療
Abstract
Background Fibrates have been shown to effectively reduce hypertriglyceridemia and increase HDL cholesterol(HDL-C)levels. This indicates that fibrates therapy complements residual cardiovascular risk beyond the HMG-CoA reductase inhibitors(statins)treatment. Therefore, statins and fibrates combination therapy is a potentially useful strategy to prevent cardiovascular events. However, adverse drug reactions(ADRs)such as transaminase and creatinine elevation have been reported to fibrates treatments. In addition, statins and fibrates combination therapy have potential untoward effects on skeletal muscle, such as elevation of creatine kinase(CK)and myopathy. Here we evaluate and predict potential ADRs of pemafibrate(Parmodia(R) tablet, also known as K-877), which was approved in July 2017. Methods Approval application data for pemafibrate were obtained from PMDA Web site (http:╱╱www.pmda.go. jp╱PmdaSearch╱iyakuSearch╱). To evaluate efficacy and safety of pemafibrate, we compared several parameters between pemafibrate and fenofibrate from meta -analysis data of eight clinical trials. These include three comparative trials investigating the efficacy of pemafibrate and fenofibrate. Results Pemafibrate has greater PPARα activation potency than other fibrates with a lower EC50 value and high degree of subtype selectivity. Although, most of fibrates primarily excreted via the kidneys and display some increase in t1╱2 in patients with renal impairment, pemafibrate primarily eliminate via the liver and had a greater safety window compared with other fibrates. Fenofibrate-treated patients demonstrated a statistically significant increase in serum AST, ALT, γ-GTP, and creatinine level, and reduction in eGFR compared with pemafibrate-treated patients at Weeks 12. Conclusions In this meta-analysis and approval application data, pemafibrate was found to be superior to other fibrates for the treatment of patients with renal impairment. In addition, low drug-drug interaction and wide safety window of pemafibrate would allow to lower risk in myopathy by pemafibrate and statins combination therapy.
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