Pharmaceutical Research

, Volume 29, Issue 12, pp 3235–3250

Inhibition of Cholesterol Absorption: Targeting the Intestine

  • Stephen D. Lee
  • Pavel Gershkovich
  • Jerald W. Darlington
  • Kishor M. Wasan
Expert Review


Atherosclerosis, the gradual formation of a lipid-rich plaque in the arterial wall is the primary cause of Coronary Artery Disease (CAD), the leading cause of mortality worldwide. Hypercholesterolemia, elevated circulating cholesterol, was identified as a key risk factor for CAD in epidemiological studies. Since the approval of Mevacor in 1987, the primary therapeutic intervention for hypercholesterolemia has been statins, drugs that inhibit the biosynthesis of cholesterol. With improved understanding of the risks associated with elevated cholesterol levels, health agencies are recommending reductions in cholesterol that are not achievable in every patient with statins alone, underlying the need for improved combination therapies. The whole body cholesterol pool is derived from two sources, biosynthesis and diet. Although statins are effective at reducing the biosynthesis of cholesterol, they do not inhibit the absorption of cholesterol, making this an attractive target for adjunct therapies. This report summarizes the efforts to target the gastrointestinal absorption of cholesterol, with emphasis on specifically targeting the gastrointestinal tract to avoid the off-target effects sometimes associated with systemic exposure.

Key words

absorption atherosclerosis cholesterol heart disease targeted therapy 



ATP-binding cassette


Acyl CoA cholesterol Acyl transferase




antisense oligonucleotides


bile acid sequestrants


coronary artery disease


low-density lipoproteins


liver X receptor


microsomal triglyceride transfer protein


Niemann Pick C 1 Like 1


nanostructured aluminosilicate


RNA interference


sterol regulatory element binding protein


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Stephen D. Lee
    • 1
  • Pavel Gershkovich
    • 1
    • 2
  • Jerald W. Darlington
    • 3
  • Kishor M. Wasan
    • 1
  1. 1.Faculty of Pharmaceutical SciencesUniversity of British ColumbiaVancouverCanada
  2. 2.School of PharmacyUniversity of NottinghamNottinghamUK
  3. 3.AMCOL International CorporationHoffman EstatesUSA

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