Comparison of lifibrol to other lipid-regulating agents in experimental animals

Effect of lifibrol on the metabolism of low density lipoproteins and cholesterol

“…The molecular mechanism of action of lifibrol is not known. Several reports from studies in tissue culture and experimental animals [4–8] suggest that lifibrol affects cholesterol metabolism in various ways; however, the drug does not resemble statins in structure and has not been convincingly shown to be an inhibitor of HMG CoA reductase. The current study was carried out to determine whether lifibrol has detectable effects on the metabolism of lipoproteins or cholesterol which give insight into the mechanisms whereby it lowers plasma LDL‐cholesterol levels.…”

“…[4] reported that lifibrol inhibits 3‐hydroxy‐3‐methyl glutaryl coenzyme A (HMG CoA), synthase in vitro . In addition, experiments in animal models have suggested that lifibrol inhibits the incorporation of acetate into aceto‐acetate and HMG CoA, suggesting inhibition of cholesterol synthesis [5–7]. On the other hand, Bell [8] reported that treatment of rats with lifibrol increases hepatic and carcass cholesterol content; this observation was attributed to an increase in synthesis of cholesterol.…”

“…On the other hand, Bell [8] reported that treatment of rats with lifibrol increases hepatic and carcass cholesterol content; this observation was attributed to an increase in synthesis of cholesterol. Although the experimental data [4–8] suggest that the drug may lead to changes in cholesterol metabolism, lifibrol does not appear to inhibit HMG CoA reductase in the same way as do statins. Investigations in animals and in tissue culture thus provide no clear mechanism whereby lifibrol therapy lowers plasma levels of LDL cholesterol.…”

Guinea Pigs as Models to Study the Hypocholesterolemic Effects of Drugs

“…Krause et al (47) conducted a study that compared the pharmacologic activities of lifibrol, lovastatin and gemfibrozil, a fibric acid derivative. Lifibrol (K12.148) is an analogue of terbufibrol that has been shown to lower LDL-C by up to 35% in healthy human volunteers without affecting plasma HDL-C and TG (31).…”

“…The US National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III emphasizes that patients with CHD, or who have a risk of CHD and LDL cholesterol (LDL-C) levels >130 mg/dL, should receive drug therapy with a goal of reducing LDL-C to <100 mg/dL (23). To date, guinea pigs have been used to analyze the effects of numerous drug treatments, including 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (6,7,(15)(16)(17)48,51,53,54,77), Acyl-CoA:Cholesterol Acyltransferase (ACAT) inhibitors (40,46), cholestyramine (27,33,80,87), fibric acids (47,82), probucol (35), and apical sodium co-dependent bile acid transporter (ASBT) inhibitors (83,84). The growing incidence of dyslipidemia in Western societies reinforces the need for an appropriate animal model for the evaluation of cholesterol lowering drugs.…”