Effect of clinofibrate, a new hypelipidemic agent, on biliary and serum lipids in patients with hyperlipidemia

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      Clinofibrate was given to 15 patients with hyperlipidemia, for 6–8 weeks at the daily daily dose of 600 mg, and its effect on 3 biliary lipid components (cholesterol, bile acids and phospholipids) and on the lithogenic index was investigated. After clinofibrate treatment, 6 of the patients were given 1.5 g/day clofibrate for 6–8 weeks to compare the effect of clofibrate with that of clinofibrate.
      The molar percentages of biliary cholesterol and phospholipids to the total. mol number of the 3 biliary lipid components decreased, and that of bile acids increased during clinofibrate administration. In this way, the molar ratio of bile acids to cholesterol increased during the treatment. Neither the lithogenic index calculated by the formula of Admirand and Small nor that of Hegardt, Dam and Holzbach was altered significantly by the treatment. There was no apparent relationship between the effect of the drug on the lithogenic index and any of the factors initial lithogenic index, rate of decrease of serum lipids, or type of hyperlipidemia.
      Although clofibrate had no significant effect on the maximum solubility of cholesterol in the bile, the molar percentage of biliary cholesterol was elevated and the lithogenic index increased as compared with the control and clinofibrate period. No significant influence on bile acid composition in the bile was observed, with either clinofibrate or clofibrate.


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        • Heady J.A.
        A cooperative trial on the primary prevention of ischemic heart disease using clofibrate-Design, methods, and progress.
        Bull. W.H.O. 1973; 48: 243
        • Cooper J.
        • Geizerova M.
        • Oliver M.F.
        Clofibrate and gallstones.
        Lancet. 1975; i: 1083
        • The Coronary Drug Project Research Group
        Gallbladder diseases as a side effect of drugs.
        N. Engl. J. Med. 1977; 296: 1185
        • Oliver M.F.
        • Heady J.A.
        • Morris J.N.
        • Cooper J.
        A cooperative trial in the primary prevention of ischemic heart disease using clofibrate.
        Brit. Heart J. 1978; 40: 1069
        • Thistle J.L.
        • Schoenfield L.J.
        Induced alterations in composition of bile of persons having cholelithiasis.
        Gastroenterology. 1971; 61: 448
        • Pertsemlidis D.
        • Panveliwalla D.
        • Ahrens E.H.
        Effects of clofibrate and of an estrogen-progestin combination of fasting biliary lipids and cholic acid kinetics in man.
        Gastroenterology. 1974; 66: 565
        • Grundy S.M.
        • Mok H.Y.I.
        Colestipol, clofibrate and phytosterols in combined therapy of hyperlipidemia.
        J. Lab. Clin. Med. 1977; 89: 354
        • Angelin B.
        • Einarsson K.
        • Leijd B.
        Biliary lipid composition during treatment with different hypolipidemic drugs.
        Europ. J. Clin. Invest. 1979; 9: 185
      1. Hypolipidemic agents and gallstones.
        Med. Lett. Drug Therap. 1977; 18: 46
        • Bennion L.J.
        • Grundy S.M.
        Risk factors for the development of cholelithiasis in man.
        N. Engl. J. Med. 1978; 299: 1161
        • Bennion L.J.
        • Grundy S.M.
        Risk factors for the development of cholelithiasis in man.
        N. Engl. J. Med. 1978; 299: 1221
        • Admirand W.H.
        • Small D.M.
        The physicochemical basis of cholesterol gallstone formation in man.
        J. Clin. Invest. 1968; 47: 1043
        • Hegardt F.G.
        • Dam H.
        The solubility of cholesterol in aqueous solutions of bile salts and lecithin.
        Z. Emaehrungwiss. 1971; 10: 223
        • Holzbach R.T.
        • Marsh M.
        • Olszewski M.
        Cholesterol solubility in bile-Evidence that supersaturated bile is frequent in healthy man.
        J. Clin. Invest. 1973; 52: 1467
        • Toki K.
        • Nakamura Y.
        • Agatsuma K.
        • Nakatani H.
        • Aono S.
        Hypolipidemic action of a new aryloxy compound (S-8527).
        Atherosclerosis. 1973; 18: 101
        • Suzuki K.
        Effect of S-8527 {1,1-bis[4′-(1″-carboxy-1″-methylpropoxy)-phenyl]-cyclohexane}, a new hypolipidemic compound, on triglyceride metabolism in rats.
        Biochem. Pharmacol. 1974; 24: 1203
        • Fukumoto Y.
        • Tarui S.
        Effect of lipoclin (S-8527) on the patients of diabetic hyperlipidemia.
        Geriat. Med. 1977; 15: 1084
        • Ogino K.
        • Fukui I.
        • et al.
        Double-blind comparative trial of S-8527 (Lipoclin®) and clofibrate on hyperlipidemia.
        Clin. Eval. 1978; 6: 483
        • Thurnberg L.A.
        • Anthony-Mote A.
        The quantitative determination of bile salts in bile using thin-layer chromatography and 3-hydroxysteroid dehydroxylase.
        Clin. Chim. Acta. 1969; 24: 253
        • Uchida K.
        • Nomura Y.
        • Kadowaki M.
        • Miyata K.
        • Miyake T.
        Effects of estradiol, dietary cholesterol and l-thyroxine on biliary bile acid composition and secretary rate, and on plasma, liver and bile cholesterol levels in rats.
        Endocrinol. Japon. 1970; 17: 107
        • Folch J.
        • Lee M.
        • Stanley G.H.S.
        A simple method for the isolation and purification of total lipids from animal tissues.
        J. Biol. Chem. 1957; 226: 497
      2. Cholesterol (Enzymatic) Technicon Method No. S.E. 4-0040 F.C. 6. Technicon Instruments Co, Tarrytown, NY1976
        • Hoeflmyar J.
        • Fried R.
        Eine Methode zur routinemaessigen Bestimmung des Lipidphosphor and Phosphatide.
        Med. Ernaehr.. 1966; 7: 1
        • Thomas P.J.
        • Hofman A.F.
        A simple calculation of the lithogenic index of bile.
        Gastroenterology. 1973; 65: 698
      3. Triglyceride (Enzymatic) Technicon Method No. S.F. 4-0039 P.A. 6. Technicon Instruments Co, Tarrytown, NY1976
        • Sakamoto S.
        • et al.
        Morphological change in the liver of rats treated with a new hypolipidemic agent S-8527.
        Atherosclerosis. 1973; 18: 109
      4. Irie, T. et al., Personal communication.

        • Hall M.J.
        • Nelson L.M.
        • Russell I.
        • Howard A.N.
        A comparison of the effect of gemfibrosil and clinofibrate on the lithogenic index of bile.
        Scot. Med. J. 1979; 24: 175
        • Schlierf G.
        • Fischer H.
        • Roche A.
        • Stiehl A.
        • Oster P.
        • Schellenberg B.
        • Vollmar J.
        Gallenlipide unter Gazafibrat.
        Münch. Med. Wschr. 1980; 122: 165
        • Schlierf G.
        • Chwat M.
        • Feuerborn E.
        • Wuelfinghof E.
        • Heuck C.C.
        • Kohlmeier M.
        • Oster P.
        • Stiehl A.
        Biliary and plasma lipids and lipid-lowering chemotherapy-Studies with clofibrate, fenofibrate and etofibrate in healthy volunteers.
        Atherosclerosis. 1980; 36: 323