Lifibrol enhances the low density lipoprotein apolipoprotein B-100 turnover in patients with hypercholesterolemia and mixed hyperlipidemia

Lifibrol (4-(4'-tert-butylphenyl)-1-(4'carboxyphenoxy)-2-butanol), a new hy pocholesterolemic drug, effectively reduces total cholesterol (CH), low den sity lipoprotein (LDL)-CH, and apolipoprotein (apo) B in experimental anima ls and in humans. The impact of Lifibrol on the metabolism of apoB-100 cont aining lipoproteins in patients with hyperlipoproteinemia using endogenous labeling with stable isotopes is examined. Kinetic studies were performed i n four male hypercholesterolemic individuals (type IIa) before and on treat ment with 450 mg of Lifibrol daily for 4 weeks, and in five male individual s suffering from mixed hyperlipidemia (type IIb) before and on therapy for 12 weeks. Kinetic parameters were estimated by multicompartmental modeling. Lifibrol therapy reduced total CH by 16% (P=0.012) in all patients, increa sed triglycerides (TG) by 11% (not significant) in type IIa patients and de creased TG by 34% (P = 0.059) in type IIb patients. During Lifibrol therapy , LDL apoB-100 concentrations decreased by 19% (P = 0.011) in all patients. The decrease in LDL apoB concentrations with Lifibrol therapy was due to a n overall increase (75%, P = 0.006) of the fractional catabolic rates (FCR) of LDL apoB. This increase was partially attenuated by a 33% increase in L DL apoB production rate (PR) (P = 0.041). The overall production of apoB in creased only slightly. Our data suggest that the major mechanism by which L ifibrol lowers LDL-CH is an increase in receptor-mediated catabolism of LDL rather than a decrease in hepatic apoB production. (C) 1999 Elsevier Scien ce Ireland Ltd. All rights reserved.