Effects of etofibrate upon the metabolism of chylomicron-like emulsions in patients with coronary artery disease.
Slow chylomicron intravascular catabolism has been associated with coronary artery disease and screening for drugs that can speed-up this process can be important. In this study, the effects of etofibrate upon chylomicron metabolism was tested by determination of the plasma kinetics of a chylomicron-like emulsion model in 12 patients with coronary artery disease, aged 59+/-11 years, (total cholesterol: 240+/-41 mg/dl; triglycerides: 188+/-42 mg/dl) submitted to a randomized, crossover, double-blind, placebo-controlled study with administration of 1 g per day etofibrate or placebo for 1-month. A 1-month washout period was inserted between the treatment periods. Patients were intravenously injected a chylomicron-like emulsion doubly labeled with 14C-cholesteryl oleate and 3H-triolein at baseline and after treatments. After etofibrate treatment, there was decrease of total cholesterol and triglyceride plasma levels and a trend to increase high-density lipoprotein cholesterol plasma levels. Etofibrate elicited 62% enhancement of post-heparin lipolytic activity and 100% increase of 3H-triglyceride fractional clearance rate compared with placebo treatment. 14C-cholesterol ester fractional clearance rate was 260% greater after etofibrate than after placebo. Therefore, a potent effect of etofibrate on both chylomicron lipolysis and remnant removal was achieved, indicating that this drug can be used to improve this metabolism in future prospective studies.
Spósito
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AC
Heart Institute (InCor), Laboratório de Metabolismo Lipídico, Instituto do Coração do Hospital das Clínicas da U.S.P., University of São Paulo Medical School, University of São Paulo, Av. Dr. Eneas C. Aguiar, Brazil.
Maranhão
R C
RC
Vinagre
C G
CG
Santos
R D
RD
Ramires
J A
JA
D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D002914:Chylomicrons / Q000008:administration & dosage / Q000187:drug effects / Q000493:pharmacokinetics*; D002995:Clofibric Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives; D003327:Coronary Disease / Q000097:blood* / Q000188:drug therapy; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D004655:Emulsions; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D015415:Biomarkers; D008076:Cholesterol, HDL; D002914:Chylomicrons; D004655:Emulsions; D014280:Triglycerides; C009746:etofibrate; D002995:Clofibric Acid; D002784:Cholesterol