Lifibrol (4-(4'-tert-butylphenyl)-1-(4'carboxyphenoxy)-2-butanol) is a new hypocholesterolemic
drug effectively reducing total
cholesterol, LDL cholesterol, 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 the metabolism of HDL
apoA-I in patients with
hyperlipoproteinemia, using endogenous labeling with stable
isotopes. Kinetic studies were performed in five male hypercholesterolemic individuals (type IIa), before and on treatment with 450 mg of
Lifibrol daily for 4 weeks and in five male individuals suffering from mixed
hyperlipidemia (type IIb), before and on
therapy, for 12 weeks.
Lifibrol reduced total
cholesterol by 14% (P=0.02) and
LDL cholesterol by 16% (P=0. 014) in all patients, and decreased
triglycerides by 34% in type IIb patients. During
Lifibrol therapy,
HDL cholesterol and
ApoA-I concentrations did not change. Tracer kinetics revealed that the fractional catabolic rate (FCR) of HDL
apoA-I increased by 22% (P=0. 013). This increase in the
apoA-I FCR was accompanied by a 23% increase in HDL
apoA-I production rate (P=0.006). We conclude that
Lifibrol, although not changing HDL steady state concentrations, enhances the turnover of
apoA-I containing HDL particles.