Grundy S M, Mok H Y
J Lab Clin Med. 1977 Feb;89(2):354-66.
Studies were carried out to determine effects of combined chemotherapy in patients with hyperlipidemia. In one study, 14 patients were treated first with colestipol and then with the combination of colestipol and clofibrate. In a second study, six patients were given clofibrate followed by addition of phytosterols. The following measurements were made in most patients: (1) plasma lipid concentrations, (2) fecal excretions of neutral steroids and bile acids, and (3) lipid composition of gallbladder bile. In six patients of the first study, hepatic secretion rates of biliary lipids and pool sizes of bile acids were also estimated. In the first study, colestipol alone caused a marked increase in fecal bile acids that resulted in a sizable decrease in plasma cholesterol concentrations (average 21 percent). In several patients, however, triglycerides were increased somewhat by colestipol. Despite interruption of the enterohepatic circulation of bile acids, the bile acid pool was not reduced, since a compensatory increase took place in bile acid synthesis. Also, except in one patient who developed gallstones following institution of colestipol, saturation of gallbladder bile with cholesterol was not markedly increased by this drug alone. Addition of clofibrate frequently produced a further decrement in plasma cholesterol, and the mild hypertriglyceridemia induced by colestipol was reversed. However, colestipol plus clofibrate usually caused a striking increase in saturation of gallbladder bile. Previous studies have shown that clofibrate causes a flux of cholesterol from tissue pools by simultaneously decreasing cholesterol synthesis and increasing its excretion. To further increase cholesterol excretion, phytosterols, which block cholesterol absorption, were added to clofibrate in the second study. Although phytosterols did not cause a further reduction in plasma cholesterol in these particular patients, they nevertheless greatly enhanced cholesterol excretion.
开展了多项研究以确定联合化疗对高脂血症患者的影响。在一项研究中，14名患者先接受考来烯胺治疗，随后接受考来烯胺与氯贝丁酯的联合治疗。在另一项研究中，6名患者先服用氯贝丁酯，随后添加植物甾醇。大多数患者进行了以下测量：（1）血浆脂质浓度，（2）中性类固醇和胆汁酸的粪便排泄量，以及（3）胆囊胆汁的脂质成分。在第一项研究的6名患者中，还估算了胆汁脂质的肝分泌率和胆汁酸池大小。在第一项研究中，单独使用考来烯胺导致粪便胆汁酸显著增加，从而使血浆胆固醇浓度大幅下降（平均21%）。然而，在几名患者中，考来烯胺使甘油三酯有所升高。尽管胆汁酸的肠肝循环被中断，但胆汁酸池并未减少，因为胆汁酸合成发生了代偿性增加。此外，除了一名在服用考来烯胺后出现胆结石的患者外，单独使用该药物并未使胆囊胆汁的胆固醇饱和度显著增加。添加氯贝丁酯通常会使血浆胆固醇进一步降低，考来烯胺所致的轻度高甘油三酯血症也会得到逆转。然而，考来烯胺加氯贝丁酯通常会使胆囊胆汁的饱和度显著增加。先前的研究表明，氯贝丁酯通过同时降低胆固醇合成并增加其排泄，使胆固醇从组织池中流出。为了进一步增加胆固醇排泄，在第二项研究中，将阻断胆固醇吸收的植物甾醇添加到氯贝丁酯中。尽管植物甾醇在这些特定患者中并未使血浆胆固醇进一步降低，但它们极大地增强了胆固醇排泄。
