Changes in plasma activities of lipolytic enzymes and lipids of normolipidemic subjects given phenobarbital, a strong microsomal inducer, alone or in combination with fenofibrate.

Heller, F R;Desager, Jean-Pierre;Harvengt, C.
(1988) International journal of clinical pharmacology, therapy, and toxicology — Vol. 26, n° 3, p. 138-142 (1988)

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  • Heller, F R
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  • Desager, Jean-PierreUCLouvain
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  • Harvengt, C.UCLouvain
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Abstract
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.
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Heller, F. R., Desager, J.-P., & Harvengt, C. (1988). Changes in plasma activities of lipolytic enzymes and lipids of normolipidemic subjects given phenobarbital, a strong microsomal inducer, alone or in combination with fenofibrate. International journal of clinical pharmacology, therapy, and toxicology, 26(3), 138-142. https://hdl.handle.net/2078.5/135473 (Original work published 1988)