Weisweiler P
Metabolic Research Munich, FRG.
Metabolism. 1989 Mar;38(3):271-4. doi: 10.1016/0026-0495(89)90086-3.
Effects on plasma lipoproteins, lecithin:cholesterol acyltransferase (LCAT), and postheparin lipase (LPL and HTGL) activities were studied in 18 patients with familial hypercholesterolemia during 8-week treatment periods with colestipol (15 g/d), fenofibrate (0.25 g/d), and colestipol plus fenofibrate. Lipoprotein lipids and apolipoproteins were determined by standard procedures, LCAT by a self-substrate method, and lipases by nonradioisotopic methods. Colestipol and fenofibrate, each given independently, caused similar percentage decreases in LDL cholesterol and apolipoprotein B: -18.4% and -8.6% v -17.4% and -10.6% Colestipol increased the VLDL cholesterol concentration, whereas fenofibrate reduced this parameter but increased HDL cholesterol and apolipoprotein A-I levels. The combination of both drugs led to a substantial fall in LDL cholesterol (-36.8%) and in apolipoprotein B (-28.3%) and maintained the other effects of fenofibrate on VLDL and HDL. Colestipol, given independently or with fenofibrate, produced an increase of the fractional esterification rate of the LCAT enzyme (+25.3% and +36.2%). Fenofibrate stimulated the postheparin LPL enzyme by +16.1% and +21.7%, respectively. This study indicates the complementarity in effectiveness when both drugs were administered together. The appropriate reduction in LDL was combined with the favorable effects on HDL in familial hypercholesterolemia.
在18例家族性高胆固醇血症患者中,研究了考来替泊(15g/d)、非诺贝特(0.25g/d)以及考来替泊加非诺贝特在8周治疗期内对血浆脂蛋白、卵磷脂胆固醇酰基转移酶(LCAT)和肝素后脂肪酶(LPL和HTGL)活性的影响。采用标准程序测定脂蛋白脂质和载脂蛋白,用自底物法测定LCAT,用非放射性同位素法测定脂肪酶。单独给予考来替泊和非诺贝特,导致低密度脂蛋白胆固醇和载脂蛋白B的降低百分比相似:分别为-18.4%和-8.6% 对比 -17.4%和-10.6%。考来替泊增加极低密度脂蛋白胆固醇浓度,而非诺贝特降低该参数,但增加高密度脂蛋白胆固醇和载脂蛋白A-I水平。两种药物联合使用导致低密度脂蛋白胆固醇(-36.8%)和载脂蛋白B(-28.3%)大幅下降,并维持了非诺贝特对极低密度脂蛋白和高密度脂蛋白的其他作用。单独给予或与非诺贝特联合给予考来替泊,均可使LCAT酶的分数酯化率增加(分别为+25.3%和+36.2%)。非诺贝特分别使肝素后LPL酶活性增加+16.1%和+21.7%。本研究表明两种药物联合使用时在疗效上具有互补性。在家族性高胆固醇血症中,适当降低低密度脂蛋白与对高密度脂蛋白的有利作用相结合。