薬理と治療

Abstract

In 2007, ezetimibe（ZETIA Tablet）, an inhibitor of small intestinal cholesterol transport （Niemann Pick C1 Like 1）, became available in Japan. Ezetimibe was reported to lower plasma LDL cholesterol level by 20％ in Western countries, but little information is available in Japan. The purpose of this study is to investigate the effect of ezetimibe monotherapy on plasma lipids（particularly LDL cholesterol and remnant cholesterol）, glycemic control and adverse reactions in Japanese hyperlipidemic patients. Twenty five patients with hyperlipidemia（male n＝14, female n＝11）were studied. Ten patients had type 2 diabetes mellitus, and they were under stable glycemic control. All patients had normal renal and liver functions. Plasma lipids and other parameters were measured before and after the treatment. Plasma remnant cholesterol was determined as RLP−cholesterol（normal range＜5.2 mg／dL）. Ezetimibe（10 mg／day after breakfast）was administered over 3 months. It significantly reduced plasma total cholesterol by 19.6％（235→189 mg／dL）, plasma LDL−cholesterol by 25.2％（151→113 mg／dL）, and plasma remnant cholesterol by 39.2％（7.9→4.8 mg／dL）. It tended to reduce plasma triglyceride by 16.7％（141→118 mg／dL）and to raise plasma HDLcholesterol by 2 mg／dL （55→57 mg／dL）, but these differences were not statistically different. Fasting plasma glucose and HbA1c were not changed in all patients or in diabetic patients before and after the treatment. Plasma ALT, AST, γ−GTP, CPK and creatinine were not changed before and after the treatment, and no adverse reactions were observed over the study period. It is concluded that the ezetimibe monotherapy is very effective to reduce not only plasma LDL−cholesterol but also plasma remnant cholesterol in Japanese hyperlipidemic patients. Ezetimibe is suggested to protect atherosclerosis since increased remnant lipoproteins which underlie hyeprtriglyceridemia are strongly atherogenic as well as LDL. （Jpn Pharmacol Ther 2008；36：411−6） KEY WORDS Ezetimibe, Hyperlipidemia, Remnant cholesterol, LDL cholesterol, Effectiveness, Safety