Colestipol, clofibrate, and phytosterols in combined therapy of hyperlipidemia.
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.
D000328:Adult; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D002994:Clofibrate / Q000627:therapeutic use*; D003084:Colestipol / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005243:Feces / Q000032:analysis; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism; D006949:Hyperlipidemias / Q000188:drug therapy*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010840:Phytosterols / Q000627:therapeutic use*; D011073:Polyamines / Q000627:therapeutic use*; D013256:Steroids / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D001647:Bile Acids and Salts; D010840:Phytosterols; D011073:Polyamines; D013256:Steroids; D014280:Triglycerides; D002784:Cholesterol; D002994:Clofibrate; D003084:Colestipol