Changes in plasma activities of lipolytic enzymes and lipids of normolipidemic subjects given phenobarbital, a strong microsomal inducer, alone or in combination with fenofibrate.
Eight male, normolipidemic, non-obese subjects were given fenofibrate (F) (300 mg daily) for eight days (period F). After a wash-out period of four weeks, phenobarbital (P) (100 mg daily) was given for eight days (period P). At the end of this period, P was continued at the same dosage but F (300 mg daily) was added and both drugs were given simultaneously for a further eight-day period (period P + F). The plasma concentrations of lipids and the plasma activities of enzymes involved in the interconversion of plasma lipoproteins: lipoprotein lipase (LPL), hepatic lipase (HL) and lecithin: cholesterol acyltransferase (LCAT) were measured before and at the end of each period of treatment. Fenofibrate induced a decrease in the plasma concentration of triglycerides (TG), total cholesterol (TC), apoB and an increase in the plasma activities of LPL and LCAT. Phenobarbital induced a decrease in the plasma concentration of TC, HDL-C and LDL-C (with an unchanged HDL-C/LDL-C ratio) and in the plasma activity of LPL. Addition of P to F did not modify the hypolipidemic action of F but the increase of LPL activity during period P + F was found to be greater than that observed during period F. It is concluded that P does not modify the serum lipoprotein pattern in a way which can be considered as beneficial in terms of atherosclerosis. By measuring the serum concentration of unconjugated bilirubin, the plasma clearance of antipyrine and the urinary excretion of 6 beta-hydroxycortisol as parameters of hepatic microsomal induction, F appeared to be a slight inducer as compared with P. Thus, enzyme induction cannot explain the changes in serum lipoproteins induced by P and does not modify the hypolipidemic action of F.
Heller
F R
FR
Laboratory of Pharmacotherapy, Catholic University of Louvain, Brussels, Belgium.
Desager
J P
JP
Harvengt
C
C
D000328:Adult; D000983:Antipyrine / Q000097:blood; D004790:Enzyme Induction / Q000187:drug effects; D011345:Fenofibrate / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008049:Lipase / Q000097:blood; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000097:blood; D008099:Liver / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010634:Phenobarbital / Q000494:pharmacology*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology*
D000960:Hypolipidemic Agents; D008055:Lipids; D011422:Propionates; C006012:fenofibric acid; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D008049:Lipase; D008071:Lipoprotein Lipase; D000983:Antipyrine; D011345:Fenofibrate; D010634:Phenobarbital