Atorvastatin enhances the plasma clearance of chylomicron-like emulsions in subjects with atherogenic dyslipidemia: relevance to the in vivo metabolism of triglyceride-rich lipoproteins

Delayed chylomicron clearance is a characteristic of patients with coronary artery disease. In vivo study of the clearance of labeled chylomicron-like emulsions constitutes a valid model system for evaluation of chylomicron catabolism. The effects of atorvastatin at low (10 mg) and high (40 mg) dose upon the intravascular metabolism and plasma kinetics of chylomicron-like emulsions were evaluated in fasting hyperlipidemic subjects ( n=45). Subjects were randomized to a 6-week treatment period with placebo ( n=15), low dose or high dose atorvastatin (10 mg/day, n=17 and 40 mg/day, n=13). The chylomicron-like emulsion, double-labeled with 14C-Cholesteryl oleate ( 14C-CE) and 3H-triolein ( 3H-TG), was injected in a bolus after a 12-h fast, and blood samples were collected up to 60 min. Plasma decay curves were determined for labeled emulsion CE and TG and residence times (RT) calculated by the occupancy principle. The 14C-CE RT was decreased by 50% after low dose atorvastatin and by 73% after atorvastatin at high dose in comparison to placebo ( P