The pharmacokinetics and pharmacodynamics of agents proven to raise high-density lipoprotein cholesterol

  • Robert W Piepho
    Address for reprints: Robert W. Piepho, PhD, University of Missouri-Kansas City School of Pharmacy, 5005 Rockhill Road, KPB, Room 101, Kansas City, Missouri 64110-2499
    School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri, USA
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      Bile acid sequestrants, fibric acid derivatives (fibrates), hydroxy-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (“statins”), and niacin are able to increase HDL-C serum concentrations to varying degrees. Bile acid sequestrants are the least effective, whereas niacin is the most powerful agent for increasing HDL-C levels. Because of 2 alternate metabolic pathways of niacin breakdown, flushing or hepatotoxicity can occur in patients taking niacin. These effects can be mediated in a carefully designed formulation of niacin that releases the drug at a predictable rate. Niacin has few drug interactions and is a relatively inexpensive means of increasing HDL-C. A combination formulation that combines niacin plus a statin has shown promise in ongoing clinical trials.
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        • Boden W.E.
        • Pearson T.A.
        Raising low levels of high-density lipoprotein cholesterol is an important target of therapy.
        Am J Cardiol. 2000; 85: 645-650
        • Bhatnagar D.
        Lipid-lowering drugs in the management of hyperlipidaemia.
        Pharmacol Ther. 1998; 79: 205-230
      1. Gaw A, Packard CJ, Shepherd J. Principles and Treatment of Lipoprotein Disorders. Fibrates. In: Schettler G, Habennicht AJR, eds. Handbook of Experimental Pharmacology. Berlin: Springer-Verlag, 1994:325–348.

        • Kumar S.
        • Derrington P.N.
        • Bhatnagar D.
        • Laing I.
        Suppression of non-esterified fatty acids to treat type A insulin resistance syndrome.
        Lancet. 1994; 343: 1073-1074
        • Staels B.
        • Dallongeville J.
        • Auwerx J.
        • Schoonjans K.
        • Leitersdorf E.
        • Fruchart J.C.
        Mechanism of action of fibrates on lipid and lipoprotein metabolism.
        Circulation. 1998; 98: 2088-2093
        • Folkers K.
        • Langsjoen P.
        • Willis R.
        • Richardson P.
        • Xia L.J.
        • Ye C.Q.
        • Tamagawa H.
        Lovastatin decreases coenzyme Q levels in humans.
        Proc Natl Acad Sci USA. 1990; 87: 8931-8934
        • Jinn F.Y.
        • Kamanna V.S.
        • Kashyap M.L.
        Niacin decreases removal of high-density lipoprotein apolipoprotein A-1 but not cholesterol ester by Hep G2 cells.
        Arterioscler Thromb Vasc Biol. 1997; 17: 2020-2028
        • Kashyap M.L.
        • Evans R.
        • Simmons P.D.
        • Kohler R.M.
        • McGovern M.E.
        New combination niacin/statin formulation shows pronounced effects on major lipoproteins and is well tolerated (abstract).
        J Am Coll Cardiol. 2000; 35: 326