Cholesterol malabsorption caused by sitostanol ester feeding and neomycin in pravastatin-treated hypercholesterolaemic patients.
Serum cholesterol values were insufficiently reduced by pravastatin in two different patient populations. Therefore, we studied whether further cholesterol reduction could be achieved by inhibiting both cholesterol synthesis (by pravastatin) and absorption (by neomycin or sitostanol ester). Thus, we measured serum cholesterol, cholesterol precursors (reflecting cholesterol synthesis), cholestanol and plant sterols (reflecting cholesterol absorption and biliary secretion) for up to 6 weeks in pravastatin-treated patients with familial hypercholesterolaemia (FH, n = 13) and with and without ileal bypass during addition of neomycin (1.5 g per day) and in another patient population of non-FH (n = 14) subjects during addition of sitostanol ester (1.5 g per day). Addition of neomycin lowered serum total, LDL and HDL cholesterol by a further 20%, and increased the pravastatin-lowered precursor:cholesterol ratios by 20% (irrespective of ileal bypass). It also reduced by 20% the plant sterol:cholesterol ratio (irrespective of ileal bypass) which was markedly increased by pravastatin alone. Pravastatin and neomycin in combination lowered total, LDL and HDL cholesterol by 45%, 53% and 17%, respectively. This combined regimen reduced the serum lathosterol:cholesterol ratio to about half of the reduction caused by pravastatin, while the elevation of the plant sterols:cholesterol ratio was less with the combination than with pravastatin alone. Changes in serum cholesterol precursor:cholesterol and plant sterol:cholesterol ratios during the combined treatment were smaller in the subgroup with ileal bypass. Addition of sitostanol ester did not lower serum total or LDL cholesterol nor the precursor:cholesterol ratios significantly, while the reduction observed in the plant sterols:cholesterol ratios was similar to that achieved with neomycin addition.(ABSTRACT TRUNCATED AT 250 WORDS)
Second Department of Medicine, University of Helsinki, Finland.
H
H
Vanhanen
D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002784:Cholesterol / Q000378:metabolism*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy* / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009355:Neomycin / Q000494:pharmacology* / Q000627:therapeutic use*; D017035:Pravastatin / Q000627:therapeutic use*; D012855:Sitosterols / Q000494:pharmacology* / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D012855:Sitosterols; D002784:Cholesterol; C021255:stigmastanol; D009355:Neomycin; D017035:Pravastatin