Effects of etofibrate upon the metabolism of chylomicron-like emulsions inpatients 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 met abolism 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 +/- 4 2 mg/dl) submitted to a randomized, crossover, double-blind, placebo-contro lled study with administration of 1 g per day etofibrate or placebo for 1-m onth. A I-month washout period was inserted between the treatment periods. Patients were intravenously injected a chylomicron-like emulsion doubly lab eled with C-14-cholesteryl oleate and H-3-triolein at baseline and after tr eatments. After etofibrate treatment, there was decrease of total cholester ol and triglyceride plasma levels and a trend to increase high-density lipo protein cholesterol plasma levels. Etofibrate elicited 62% enhancement of p ost-heparin lipolytic activity and 100% increase of H-3-triglyceride fracti onal clearance rate compared with placebo treatment. C-14-cholestrrol ester fractional clearance rate was 260% greater after etofibrate than after pla cebo. Therefore, a potent effect of etofibrate on both chylomicron lipolysi s and remnant removal was achieved, indicating that this drug can be used t o improve this metabolism in future prospective studies. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.