The effects of gemfibrozil upon the metabolism of chylomicron-like emulsions in patients with endogenous hypertriglyceridemia

Objective: To evaluate the effects of gemfibrozil upon the intravascular metabolism of chylomicron-like emulsions in endogenous hypertriglyceridemia. Methods: We evaluated the plasma kinetics of a chylomicron-like emulsion in 39 subjects: 27 hypertriglyceridemics, total cholesterol (TC) expressed as median (%25; %75) 7.47 (6.1; 8.19) mmol/l and plasma triglycerides (TG) 4.28 (3.6; 18.5) mmol/l and in 12 normolipidemics, TC 4.7 (3.85; 5.37) mmol/l and TG 0.91 (0.64; 1.75) mmol/l. Hypertriglyceridemics were evaluated at baseline and after a 30-day 1200-mg/day gemfibrozil (n = 8) or placebo treatment (n = 7). The emulsion labelled with ¹⁴C-cholesteryl oleate (¹⁴C-CO) and ³H-triolein (³H-TO) was injected intravenously after a 12-h fast. The plasma kinetics of ³H-TO and ¹⁴C-CO were determined to assess, respectively, lipolysis and clearance of chylomicron and remnants by compartmental analysis. Results: The residence times (in minutes) of ³H-TO and ¹⁴C-CO of hypertriglyceridemics were roughly twice the values of normolipidemics, i.e. 8.0 (5.5; 12.0) versus 15.0 (11.0; 24.0) and 21.5 (14.0; 33.0) versus 44.0 (32.0; 72.0), P = 0.001. Gemfibrozil treatment of hypertriglyceridemic patients reduced the residence times of ³H-TO and ¹⁴C-CO, respectively, by 46% (P = 0.003) and 53% (P = 0.008). Effects were noted on the slow phase of emulsion plasma removal, which was reduced in hypertriglyceridemics. After treatment, the emulsion residence times determined in hypertriglyceridemics attained the values of the normolipidemic group. Conclusions: Gemfibrozil treatment normalised the defects in chylomicron-like emulsion catabolism observed in endogenous hypertriglyceridemia patients.