Document Detail


Effects of AOMA on cholesterol metabolism in man.
MedLine Citation:
PMID:  7087795     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A new cholesterol-lowering agent, surfomer (AOMA), has been developed that blocks cholesterol absorption and lowers plasma cholesterol in animals. To evaluate AOMA in man, we studied its effects on plasma cholesterol, cholesterol absorption, fecal excretion of cholesterol and its bacterial degradation products, coprostanol and coprostanone, and percent saturation of gallbladder bile with cholesterol in 20 individuals chosen for hyperlipidemia. These patients had low density lipoprotein cholesterol (LDL-C) of 215 +/- 29 mg/dl. Two dose levels of AOMA were compared (10.8 and 5.4 grams daily), each for 1 mo in a study that combined features of inpatient and outpatient investigation. AOMA was tolerated well by all volunteers. There was a statistically significant correlation between percent absorption and LDL-C in both the control and AOMA treated states. AOMA lowered mean plasma cholesterol and LDL-C by 9.1% and 12.9% at the high dose and by 6.4% and 8.3% at the low dose, respectively. Triglyceride (control = 223 +/- 58 mg/dl, treatment = 232 +/- 85 mg/dl), high density lipoprotein cholesterol (HDL-C: control = 50 +/- 11 mg/dl, treatment = 50 +/- 13 mg/dl), and other lipoprotein lipids were not affected. AOMA lowered cholesterol absorption by 25% on the high dose. For 18/20 patients there was a statistically significant (p less than 0.001) correlation (r = 0.74) between percent LDL-C reduction and percent absorption inhibition. For these patients, presumably, variable effectiveness of the agent in inhibiting absorption was the most important predictor of individual responsiveness although individual variation in other cholesterol regulatory mechanisms also played a role. Two other patients showed marked LDL-C reduction at unusually low levels of absorption inhibition. We also had the opportunity to compare the effects of AOMA with neomycin in 8 volunteers. Neomycin was 50% more effective in lowering LDL-C than AOMA; however, it was twice as effective in inhibition absorption as well. AOMA dramatically reduced fecal excretion of cholesterol bacterial conversion products; whereas cholesterol per se accounted for only 50% of total neutral steroid excretion in the control state, it accounted for 93% of steroid excretion when patients were administered 10.8 grams of AOMA daily. In four patients studied there was no adverse effect of AOMA on gallbladder saturation with cholesterol; in fact, the percent saturation tended to decrease with AOMA in these four patients.
Authors:
J R Crouse; S M Grundy; J H Johnson
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Metabolism: clinical and experimental     Volume:  31     ISSN:  0026-0495     ISO Abbreviation:  Metab. Clin. Exp.     Publication Date:  1982 Jul 
Date Detail:
Created Date:  1982-08-14     Completed Date:  1982-08-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375267     Medline TA:  Metabolism     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  733-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Bile / analysis
Cholesterol / metabolism*
Cholesterol, LDL
Feces / analysis
Female
Humans
Hypercholesterolemia / drug therapy*
Hyperlipidemias / drug therapy*
Intestinal Absorption
Lipoproteins, LDL / metabolism
Male
Middle Aged
Neomycin / therapeutic use
Polymers / therapeutic use*
Succinates / therapeutic use*
Grant Support
ID/Acronym/Agency:
HL-141297/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cholesterol, LDL; 0/Lipoproteins, LDL; 0/Polymers; 0/Succinates; 1404-04-2/Neomycin; 57-88-5/Cholesterol; 71251-04-2/surfomer

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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