HDL steady state levels are not affected, but HDL apoA-I turnover is enhanced by Lifibrol in patients with hypercholesterolemia and mixed hyperlipidemia

Lifibrol (4-(4'-tert-butylphenyl)-1-(4'carboxyphenoxy)-2-butanol) is a new hypocholesterolemic drug effectively reducing total cholesterol. LDL choles terol, and apolipoprotein (apo) B in experimental animals and in humans. In contrast to fibrates and HMG-CoA reductase inhibitors the cholesterol and triglyceride lowering effect of Lifibrol is not accompanied by increases in HDL cholesterol and apoA-I levels. We examined the impact of Lifibrol on t he metabolism of HDL apoA-I in patients with hyperlipoproteinemia, using en dogenous labeling with stable isotopes. Kinetic studies were performed in f ive male hypercholesterolemic individuals (type IIa), before and on treatme nt with 450 mg of Lifibrol daily for 4 weeks and in five male individuals s uffering from mixed hyperlipidemia (type IIb), before and on therapy, for 1 2 weeks. Lifibrol reduced total cholesterol by 14% (P = 0.02) and LDL chole sterol by 16% (P = 0.014) in all patients, and decreased triglycerides by 3 4% in type IIb patients. During Lifibrol therapy, HDL cholesterol and ApoA- I concentrations did not change. Tracer kinetics revealed that the fraction al catabolic rate (FCR) of HDL apoA-I increased by 22% (P = 0.013). This in crease in the apoA-I FCR was accompanied by a 23% increase in HDL apoA-I pr oduction rate (P = 0.006). We conclude that Lifibrol, although not changing HDL steady state concentrations, enhances the turnover of apoA-I containin g HDL particles. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved .