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((More citations needed|date=October 2023))

'''Cholesterol absorption inhibitors''' are a class of compounds that prevent the uptake of [[cholesterol]] from the small intestine into the circulatory system. Most of these molecules are [[monobactams]] but show no [[antibiotic]] activity. An example is [[ezetimibe]] (SCH 58235)<ref name="pmid11901097">((cite journal |vauthors=Patrick JE, Kosoglou T, Stauber KL |title=Disposition of the selective cholesterol absorption inhibitor ezetimibe in healthy male subjects |journal=Drug Metab. Dispos. |volume=30 |issue=4 |pages=430–7 |date=April 2002 |pmid=11901097 |doi= 10.1124/dmd.30.4.430|s2cid=30862556 |display-authors=etal|url=http://pdfs.semanticscholar.org/dd8b/416bac0b0bc3c5e0cf9ea5d6d0364a1560d7.pdf |archive-url=https://web.archive.org/web/20190304141956/http://pdfs.semanticscholar.org/dd8b/416bac0b0bc3c5e0cf9ea5d6d0364a1560d7.pdf |url-status=dead |archive-date=2019-03-04 ))</ref><ref name="pmid12423709">((cite journal |vauthors=Dujovne CA, Ettinger MP, McNeer JF |title=Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia |journal=Am. J. Cardiol. |volume=90 |issue=10 |pages=1092–7 |date=November 2002 |pmid=12423709 |doi= 10.1016/S0002-9149(02)02798-4|display-authors=etal))</ref><ref name="pmid9526571">((cite journal |vauthors=Rosenblum SB, Huynh T, Afonso A |title=Discovery of 1-(4-fluorophenyl)-(3R)-[3-(4-fluorophenyl)-(3S)-hydroxypropyl]-(4S)-(4 -hydroxyphenyl)-2-azetidinone (SCH 58235): a designed, potent, orally active inhibitor of cholesterol absorption |journal=J. Med. Chem. |volume=41 |issue=6 |pages=973–80 |date=March 1998 |pmid=9526571 |doi=10.1021/jm970701f|display-authors=etal))</ref><ref name="pmid14604738">((cite journal |vauthors=Jeu L, Cheng JW |title=Pharmacology and therapeutics of ezetimibe (SCH 58235), a cholesterol-absorption inhibitor |journal=Clin Ther |volume=25 |issue=9 |pages=2352–87 |date=September 2003 |pmid=14604738 |doi= 10.1016/S0149-2918(03)80281-3))</ref> Another example is [[Sch-48461]].<ref name="pmid7669087">((cite journal |vauthors=Salisbury BG, Davis HR, Burrier RE |title=Hypocholesterolemic activity of a novel inhibitor of cholesterol absorption, SCH 48461 |journal=Atherosclerosis |volume=115 |issue=1 |pages=45–63 |date=May 1995 |pmid=7669087 |doi= 10.1016/0021-9150(94)05499-9|display-authors=etal))</ref> The "Sch" is for [[Schering-Plough]], where these compounds were developed.
[[Phytosterols]] are also cholesterol absorption inhibitors.

Viscous [[soluble fiber]] is available in foods or [[fiber supplement]]s and can reduce LDL-C. It is hypothesized that this effect is by binding to [[bile acids]] and preventing their resorption.<ref>((cite journal |last1=Moreyra |first1=Abel E. |title=Effect of Combining Psyllium Fiber With Simvastatin in Lowering Cholesterol |journal=Archives of Internal Medicine |date=23 May 2005 |volume=165 |issue=10 |pages=1161 |doi=10.1001/archinte.165.10.1161 |url=https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486567))</ref> [[Psyllium]] reduces LDL-C by 0.33 mmol/l (12.5 mg/dl) and also reduces [[apolipoprotein B]], leading one systematic review to conclude that it "effectively improves conventional and alternative lipids markers, potentially delaying the process of atherosclerosis-associated CVD risk in those with or without hypercholesterolemia".<ref>((cite journal |last1=Jovanovski |first1=Elena |last2=Yashpal |first2=Shahen |last3=Komishon |first3=Allison |last4=Zurbau |first4=Andreea |last5=Blanco Mejia |first5=Sonia |last6=Ho |first6=Hoang Vi Thanh |last7=Li |first7=Dandan |last8=Sievenpiper |first8=John |last9=Duvnjak |first9=Lea |last10=Vuksan |first10=Vladimir |title=Effect of psyllium (Plantago ovata) fiber on LDL cholesterol and alternative lipid targets, non-HDL cholesterol and apolipoprotein B: a systematic review and meta-analysis of randomized controlled trials |journal=The American Journal of Clinical Nutrition |date=1 November 2018 |volume=108 |issue=5 |pages=922–932 |doi=10.1093/ajcn/nqy115 |pmid=30239559 |issn=1938-3207|doi-access=free ))</ref> Another soluble fiber, [[konjac]] [[glucomannan]], reduces LDL by 10 percent.<ref>((cite journal |last1=Ho |first1=Hoang Vi Thanh |last2=Jovanovski |first2=Elena |last3=Zurbau |first3=Andreea |last4=Blanco Mejia |first4=Sonia |last5=Sievenpiper |first5=John L. |last6=Au-Yeung |first6=Fei |last7=Jenkins |first7=Alexandra L. |last8=Duvnjak |first8=Lea |last9=Leiter |first9=Lawrence |last10=Vuksan |first10=Vladimir |title=A systematic review and meta-analysis of randomized controlled trials of the effect of konjac glucomannan, a viscous soluble fiber, on LDL cholesterol and the new lipid targets non-HDL cholesterol and apolipoprotein B |journal=The American Journal of Clinical Nutrition |date=May 2017 |volume=105 |issue=5 |pages=1239–1247 |doi=10.3945/ajcn.116.142158 |pmid=28356275 |issn=1938-3207|doi-access=free ))</ref>

==Physiology==
There are two sources of cholesterol in the upper intestine: dietary (from food) and [[biliary]] (from bile).  Dietary cholesterol, in the form of [[lipid]] emulsions, combines with [[Bile acid|bile salts]], to form bile salt [[micelles]] from which cholesterol can then be absorbed by the intestinal [[enterocyte]].

Once absorbed by the enterocyte, cholesterol is reassembled into intestinal [[lipoproteins]] called [[chylomicrons]].  These [[chylomicron]]s are then secreted into the [[lymphatics]] and circulated to the liver.  These cholesterol particles are then secreted by the liver into the blood as [[VLDL]] particles, precursors to [[LDL]].

As a class, cholesterol absorption inhibitors block the uptake of micellar cholesterol, thereby reducing the incorporation of cholesterol esters into chylomicron particles. By reducing the cholesterol content in chylomicrons and chylomicron remnants, cholesterol absorption inhibitors effectively reduce the amount of cholesterol that is delivered back to the liver.

The reduced delivery of cholesterol to the liver increases hepatic LDL receptor activity and thereby increases clearance of circulating LDL.  The net result is a reduction in circulating LDL particles.

==Importance==
Managing cholesterol at the site of absorption is an increasingly popular strategy in the treatment of [[hypercholesterolemia]] ((Citation needed|date=December 2015)).  Cholesterol absorption inhibitors are known to have a synergistic effect when combined a class of [[antihyperlipidemics]] called [[statins]], to achieve an overall serum cholesterol target. For statin-resistant or statin-sensitive populations that are characterized by low one-year compliance rates, such a combination therapy is proving to be especially effective ((Citation needed|date=December 2015)).
==See also==
* [[Ezetimibe]] (Zetia) - one of the most successfully selling drugs in this class

==References==
((reflist|2))

((Lipid modifying agents))

[[Category:Hypolipidemic agents]]

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