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Evaluation of the hypolipidemic activity of xenalipin in experimental animals

  • Michael C. Lewis
    Correspondence
    Correspondence address: Mr. Michael C. Lewis, Department of Pharmacology, The Wellcome Research Laboratories, Burroughs Wellcome Co., Research Triangle Park, NC 27709, U.S.A.
    Affiliations
    Departments of Pharmacology, Organic Chemistry, The Wellcome Research Laboratories, Burroughs Wellcome Co., Research Triangle Park, NC 27709 U.S.A.
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  • Gordon L. Hodgson
    Affiliations
    Department of Organic Chemistry, The Wellcome Research Laboratories, Burroughs Wellcome Co., Research Triangle Park, NC 27709 U.S.A.
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  • Thomas K. Shumaker
    Affiliations
    Department of Organic Chemistry, The Wellcome Research Laboratories, Burroughs Wellcome Co., Research Triangle Park, NC 27709 U.S.A.
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  • Donald H. Namm
    Affiliations
    Departments of Pharmacology, Organic Chemistry, The Wellcome Research Laboratories, Burroughs Wellcome Co., Research Triangle Park, NC 27709 U.S.A.
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      Abstract

      Xenalipin (4'-trifluoromethyl-2-biphenylcarboxylic acid) is a chemically novel compound which has been found to be an effective hypolipidemic agent in two animal species. Significant reductions in serum cholesterol and triglycerides were observed in cholesterol-cholic acid-fed rats following oral doses of 10–30 mg/kg/day. Xenalipin was considerably more potent than clofibrate, nicotinic acid, and cholestyramine in the same model. Lipoprotein analysis showed that xenalipin reduced cholesterol and protein content in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL). Triglycerides were reduced in VLDL and IDL. Xenalipin was also effective in reducing serum cholesterol and triglyceride concentrations in normocholesterolemic rats. In diet-induced hypercholesterolemic African green monkeys, xenalipin at oral doses of 15–60 mg/kg b.i.d. reduced serum LDL-cholesterol concentrations. These results suggest that xenalipin has a profile of activity which would be beneficial in therapy for hyperlipidemia.

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