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.
Santos
R D
RD
The Heart Institute of the Medical School Hospital (InCor), University of São Paulo, São Paulo, Brazil.
Ventura
L I
LI
Spósito
A C
AC
Schreiber
R
R
Ramires
J A
JA
Maranhão
R C
RC
D000328:Adult; D000368:Aged; D001053:Apolipoproteins / Q000097:blood; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D002914:Chylomicrons / Q000493:pharmacokinetics*; D003198:Computer Simulation; D005217:Fat Emulsions, Intravenous / Q000493:pharmacokinetics; D005260:Female; D015248:Gemfibrozil / Q000627:therapeutic use*; D006801:Humans; D015228:Hypertriglyceridemia / Q000188:drug therapy* / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D018709:Statistics, Nonparametric; D014280:Triglycerides / Q000097:blood
D001053:Apolipoproteins; D002914:Chylomicrons; D005217:Fat Emulsions, Intravenous; D000960:Hypolipidemic Agents; D014280:Triglycerides; D002784:Cholesterol; D015248:Gemfibrozil