title: Lowering LDL cholesterol, but not raising LDL receptor activity, by ezetimibe.
abstract: BACKGROUND
  Ezetimibe, an inhibitor of intestinal cholesterol absorption, is effective in lowering serum low-density lipoprotein (LDL) cholesterol with or without coadministration of statin. Ezetimibe-plus-statin therapy enhances LDL receptor activity, but it is still unclear whether ezetimibe alone enhances LDL receptor activity, resulting in LDL cholesterol decrease.
  
  
  OBJECTIVE
  We investigated whether ezetimibe lowers serum LDL cholesterol by raising LDL receptor activity in humans.
  
  
  METHODS
  Patients with hypercholesterolemia (n = 28; age [mean ± SD], 61.6 ± 13.0 years; 57% men) were treated with ezetimibe (10 mg/d) for 4 months. Before and after the treatment, serum LDL cholesterol, apolipoprotein B (apo B), and apolipoprotein C-II (apo C-II) were measured. LDL receptor activities were estimated with the equation we reported previously as follows: LDL receptor activity (represented as a percentage of normocholesterolemic subjects) = 63.595 + apo C-II (in mg/dL) × 13.459-apo B (in mg/dL) × 0.366.
  
  
  RESULTS
  By the treatment of ezetimibe, LDL cholesterol (176.8 ± 17.9 vs 138.0 ± 19.7 mg/dL) was lowered 21.9% significantly (P < .01). The estimated LDL receptor activities before and after the ezetimibe treatment were 86.8% ± 21.4% and 89.6% ± 19.7%, respectively, with no significant difference between them (P = .13).
  
  
  CONCLUSIONS
  Ezetimibe lowered LDL cholesterol significantly in patients with hypercholesterolemia without raising LDL receptor activity. The enhancement of LDL receptor activity is less involved in the pharmacologic action of ezetimibe.
authors: Department of Internal Medicine, Tokyo Ariake University of Medical and Health Sciences, 2-9-1 Ariake, Koto-ku, Tokyo 135-0063, Japan. Electronic address: zh2h-hys@asahi-net.or.jp.
authors: Hiroshi
authors: H
authors: Hayashi
authors: Mitsunobu
authors: M
authors: Kawamura
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D053304:Apolipoprotein C-II / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D001384:Azetidines / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood*; D004334:Drug Administration Schedule; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011973:Receptors, LDL / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D053304:Apolipoprotein C-II; D001055:Apolipoproteins B; D001384:Azetidines; D008078:Cholesterol, LDL; D011973:Receptors, LDL; C054300:apolipoprotein C-II (St Michael); D000069438:Ezetimibe
keywords: Apolipoproteins; Ezetimibe; LDL; LDL receptors; Lipoproteins; Pharmacology; Receptors