Effect of Phenobarbitone on Plasma Lipids in Normal Subjects

Abstract

1. Phenobarbitone in a dose of 180 mg daily was administered to ten normal subjects for 3 weeks. There was a significant increase in total plasma cholesterol, plasma low-density-lipoprotein cholesterol, plasma low-density-lipoprotein (LDL) triglycerides and plasma LDL protein. The increase in plasma LDL cholesterol accounted for the increase in total plasma cholesterol. There was a significant reduction in the ratio of LDL cholesterol to LDL protein. 2. No significant changes were observed in total plasma triglycerides, plasma very-low-density-lipoprotein (VLDL) triglycerides, plasma VLDL cholesterol or plasma VLDL protein. 3. Evidence that drug-metabolizing enzymes were induced by phenobarbitone was provided by an increase in antipyrine clearance. No relationship was observed between changes in plasma cholesterol and changes in antipyrine clearance. Serum gamma-glutamyl transpeptidase was also increased after phenobarbitone administration, the increase being unrelated to changes in antipyrine clearance or plasma cholesterol.

Effect of Phenobarbitone on Plasma Apolipoprotein B and Plasma High-Density-Lipoprotein Cholesterol in Normal Subjects

“…The increase in plasma and LDL apolipoprotein B concentrations after the administration of phenobarbitone for 3 weeks confirms the earlier observations that phenobarbitone affects LDL metabolism in man (Miller & Nestel, 1973;Durrington et al, 1976a). In the present study, an increase in serum HDL cholesterol was also found.…”

“…Total plasma cholesterol and triglycerides, plasma very-low-density lipoprotein (VLDL) cholesterol, triglycerides and protein and LDL cholesterol, triglycerides and protein, antipyrine clearance and serum y-glutamyl transpeptidase were the subject of an earlier report (Durrington et al, 1976a). The present study concerns concentrations of total plzsma apolipoprotein B and plasma VLDL and LDL apolipoprotein B and of plasma HDL cholesterol measured initially and at the end of the period on phenobarbitone.…”

“…Workers exposed to pesticides have also been found to have raised serum HDL cholesterol (Carlson & Kolmodin-Hedman, 1972). In the present report, samples from an earlier study (Durrington et al, 1976a) were analysed in order to investigate the effects of phenobarbitone on plasma HDL cholesterol. Plasma concentrations of apoliprotein B were also determined to discover whether the rise in LDL cholesterol, which had previously been observed, was accompanied by a similar rise in apolipoprotein B, which is the principal component of the protein moiety of LDL.…”

“…Phenobarbitone has previously been reported to raise concentrations of total serum cholesterol and serum low-density-lipoprotein (LDL) cholesterol in man (Miller & Nestel, 1973;Durrington, Roberts, Jackson, Branch & Hartog, 1976a). Phenytoin, another microsomal enzyme-inducing drug, has also been reported to increase serum cholesterol concentrations (Pelkonen, Fogelholm & Nikkila, 1975), and more recently to raise serum highdensity-lipoprotein (HDL) cholesterol concentrations (Nikkila, Kaste, Ehnholm & Viikari, 1978).…”

Plasma High-Density Lipoprotein Cholesterol in Epileptics Treated with Various Anticonvulsants

“…Studies on anticonvulsants have demon strated elevated serum cholesterol and triglycer ide levels in healthy subjects and patients with epilepsy (4,12,16). High plasma HDL choles terol levels have been measured in subjects undergoing phenytoin treatment (15).…”