Effects of colesevelam HC1 on sterol and bile acid excretion in patients with type IIa hypercholesterolemia.
Colesevelam HC1 is a potent bile acid-binding polymer. This study's aim was to determine effects of colesevelam HCl on sterol and bile acid excretion in patients with type IIa hypercholesterolemia. Twenty-four patients (low-density lipoprotein cholesterol, 130 to 220 mg/dL) enrolled in an open-label, parallel-design study, entered an American Heart Association/National Cholesterol Education Program diet for 6 weeks and were randomized to colesevelam HCl, 2.3 or 3.8 g/day for 4 weeks. In an apparent dose-related manner, respective mean serum concentrations HCl of low-density lipoprotein cholesterol decreased by 10% (P < 0.01) and 13% (P = 0.05), mean total cholesterol levels decreased by 4.9% (P = 0.05) and 6.1% (P = 0.09), and total fecal bile acid excretion showed median changes of +324% (P < 0.05) and +316% (P < 0.05). Colesevelam HCl did not affect fecal neutral sterol or fecal fatty acid excretion; however, 24-hr urinary mevalonic acid levels significantly increased in both treatment groups (P < 0.05). The cholesterol-lowering action of colesevelam HCl appears to be mediated through increased bile acid excretion.
Donovan
J M
JM
Genzyme Drug Discovery and Development, Waltham, Massachusetts 02451, USA. joanne.donovanMD@genzyme.com
Von Bergmann
K
K
Setchell
K D R
KD
Isaacsohn
J
J
Pappu
A S
AS
Illingworth
D R
DR
Olson
T
T
Burke
S K
SK
D000499:Allylamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D000069472:Colesevelam Hydrochloride; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013261:Sterols / Q000378:metabolism*; D016896:Treatment Outcome
D001647:Bile Acids and Salts; D008078:Cholesterol, LDL; D013261:Sterols; D000499:Allylamine; D002784:Cholesterol; D000069472:Colesevelam Hydrochloride