Heller F R, Desager J P, Harvengt C
Metabolism. 1981 Jan;30(1):67-71. doi: 10.1016/0026-0495(81)90221-3.
Plasma lipids and lipoprotein cholesterol concentrations and lecithin:cholesterol acyltransferase activity were measured in 7 normolipidemic subjects before, and 7 days after, the administration of fenofibrate (300 mg daily) and colestipol (15 g daily) taken separately or simultaneously. Fenofibrate provoked a significant decrease in the mean plasma triglycerides (26%) and cholesterol (10%) concentration; only plasma cholesterol concentrations were significantly lowered by colestipol (26%). The cholesterol lowering effects of the two drugs were additive as was observed when colestipol was added to fenofibrate. The mean plasma high density lipoprotein cholesterol (HDL-C) concentration was significantly increased by fenofibrate (10%) and when colestipol was added to fenofibrate (15%), but not by colestipol alone. Both fenofibrate and colestipol caused significant reduction of the mean plasma low density lipoprotein cholesterol (LDL-C) concentration and the mean plasma LDL-C/HDL-C ratio (13% and 18%, respectively, with fenofibrate, 44% and 52% with colestipol, and 53% and 62% with colestipol added to fenofibrate). The mean plasma fractional esterification rate was significantly increased by 25% and 12%, respectively, with fenofibrate and colestipol when taken separately, and still more (91%) when colestipol was added to fenofibrate. The mean plasma molar esterification rate was significantly lowered by colestipol, but remained unchanged with the other drug regimens. This study shows that fenofibrate and colestipol given to normolipidemic subjects can induce in a very short period of time (7 days) marked changes in lipoprotein metabolism. Interpretations of the findings in relation to lipoprotein metabolism are discussed.
在7名血脂正常的受试者单独或同时服用非诺贝特(每日300毫克)和考来替泊(每日15克)之前及之后7天,测量了血浆脂质、脂蛋白胆固醇浓度以及卵磷脂胆固醇酰基转移酶活性。非诺贝特使平均血浆甘油三酯浓度显著降低(26%),胆固醇浓度降低(10%);考来替泊仅使血浆胆固醇浓度显著降低(26%)。两种药物的降胆固醇作用具有相加性,如将考来替泊添加到非诺贝特中时所观察到的那样。非诺贝特使平均血浆高密度脂蛋白胆固醇(HDL-C)浓度显著升高(10%),当将考来替泊添加到非诺贝特中时升高幅度更大(15%),但考来替泊单独使用时无此作用。非诺贝特和考来替泊均使平均血浆低密度脂蛋白胆固醇(LDL-C)浓度以及平均血浆LDL-C/HDL-C比值显著降低(非诺贝特分别降低13%和18%,考来替泊降低44%和52%,考来替泊添加到非诺贝特中时降低53%和62%)。单独服用非诺贝特和考来替泊时,平均血浆分数酯化率分别显著升高25%和12%,当考来替泊添加到非诺贝特中时升高幅度更大(91%)。考来替泊使平均血浆摩尔酯化率显著降低,但其他药物治疗方案使其保持不变。本研究表明,给予血脂正常的受试者非诺贝特和考来替泊可在非常短的时间内(7天)诱导脂蛋白代谢发生显著变化。讨论了这些发现与脂蛋白代谢相关的解释。