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PubMed1988

[Pharmacological investigation of bezafibrate, a hypolipidemic agent (2). Mechanism of the hypolipidemic action of bezafibrate in rats].

The mechanism of the hypolipidemic action of bezafibrate was investigated in rats. Bezafibrate decreased the incorporation of 14C-acetic acid into the liver and serum triglyceride and inhibited liver acetyl CoA carboxylate activity. Bezafibrate increased liver beta-oxidation, but it had no effect on lipolysis and triglyceride secretion from the liver. Bezafibrate accelerated the elimination of serum triglyceride in Intralipid injected rats and increased tissue lipoprotein lipase activity. Bezafibrate decreased the incorporation of 14C-acetic acid into liver cholesterol and inhibited liver HMG-CoA reductase activity. Bezafibrate had no effect on cholesterol absorption and excretion. These results suggest that the hypotriglyceridemic actions of bezafibrate are due to inhibition of triglyceride synthesis and acceleration of triglyceride elimination and that the hypocholesterolemic action of bezafibrate is mainly due to inhibition of liver HMG-CoA reductase activity.

Acetates↗

PubMed1986

Long-term effects of bezafibrate and of a bezafibrate and cholestyramine combination on lipids and lipoprotein lipids in type IIa hypercholesterolaemic patients.

Eighteen hypercholesterolaemic patients have been treated for four months with bezafibrate 200 mg thrice daily. After one month of therapy, total cholesterol (T-C) decreased on the average by 19%, total triglycerides (T-TG) by 28%, very low density lipoprotein-TG by 47%, LDL-C by 25% and HDL3-C increased by 16%. At the fourth month of therapy the lipoprotein pattern was unchanged as compared to the one observed at the first month. In 12 patients T-C was normalized by bezafibrate and the patients continued the treatment for one year without experiencing further changes in lipoprotein pattern. Six patients with severe hypercholesterolaemia (mean baseline T-C of 11.51 +/- 0.63 mmoles/l) failed to adequately respond to bezafibrate treatment and were put on the combined bezafibrate 600 mg/day and cholestyramine 16g/day therapy. During bezafibrate their T-C decreased on the average by 21% and LDL-C by 23% and during the combined therapy by 33% and by 37% respectively, as compared to the baseline values. Combined bezafibrate and cholestyramine treatment seems then to be more effective than bezafibrate alone in decreasing serum cholesterol and may be useful in patients with severe hypercholesterolaemia.

Adult↗

PubMed1988

[Pharmacological investigation of bezafibrate, a hypolipidemic agent (1). Effects of bezafibrate on normal and experimental hyperlipidemia in rats].

The hypolipidemic effects of bezafibrate were examined in normal rats and an experimentally induced hyperlipidemic model of rats. Oral administration of bezafibrate at 1 mg/kg/day or more to normal rats for 7 days significantly decreased serum triglyceride (TG) and at 3 mg/kg/day or more for 7 days caused significant reduction of serum total cholesterol (TC). A single oral dose of 100 mg/kg of bezafibrate significantly inhibited the increase of serum TC and TG in hyperlipidemic rats induced by Triton WR-1339. When normal rats were given 75% fructose solution for 7 days, serum TG increased in concentration about four times. Oral administration of bezafibrate for 7 days at 1 mg/kg/day or more inhibited the increase of serum TG in this model. Serum TC increased in concentration about twice in 1% cholesterol diet-fed rats for 8 weeks. Oral administration of bezafibrate at 30 mg/kg/day or more inhibited the increase of serum TC. These results suggest that bezafibrate is effective in the treatment of hyperlipidemia.

Administration, Oral↗

PubMed1992

Effects of combined bezafibrate-simvastatin appraised in healthy subjects.

The occurrence of clinical and biochemical side effects of bezafibrate (400 mg daily) or simvastatin (20 mg daily) alone or combined was appraised in 13 healthy male normolipidemic subjects according to a single blind design. Each period of 2 weeks of treatment with bezafibrate or simvastatin or bezafibrate plus simvastatin was followed by a period of placebo (1 week). No subjects experienced myalgia or muscle weakness. Plasma creatine kinase (CK) elevations, particularly skeletal muscle CK (CK-MM), were observed in 6 subjects: 11 times during different placebo periods, 5 times on bezafibrate, 4 times on simvastatin, and 4 times on combined bezafibrate-simvastatin, but never reached 1,600 IU/L. Only a trend to an increase of CK mean values on combined bezafibrate-simvastatin was shown. The hepatic transaminase and gamma-glutamyltransferase activities remained unmodified throughout the trial, unlike alkaline phosphatase activity, which fell on bezafibrate and on bezafibrate plus simvastatin. The low-density lipoprotein cholesterol level was more reduced with simvastatin than with bezafibrate. The addition of bezafibrate to simvastatin did not decrease it further. Lecithin:cholesterol acyltransferase activity expressed as fractional esterification rate was enhanced only on simvastatin and bezafibrate-simvastatin.

Adult↗

PubMed1994

Effects of bezafibrate therapy on subfractions of plasma low-density lipoprotein and high-density lipoprotein, and on activities of lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein in patients with hyperlipoproteinemia.

We investigated the effects of 12 weeks of bezafibrate treatment on plasma lipoprotein subfraction levels and on activities of LCAT and CETP in 25 patients with hyperlipoproteinemia. Bezafibrate reduced plasma levels of VLDL-TC and VLDL-TG by 69% and 66% (P < 0.001) and plasma levels of IDL-TC and IDL-TG were decreased by 37% and 31% (P < 0.01). Bezafibrate had no significant effects on plasma levels of LDL1 (1.019 < d < 1.045)-TC and LDL1-TG in the study population as a whole but significantly increased the plasma level of LDL1-TC in the subgroup of 9 patients with type IV hyperlipoproteinemia. Bezafibrate reduced plasma levels of LDL2 (1.045 < d < 1.063)-TC, LDL2-TG by 48% and 44% (P < 0.001) in both type II and type IV hyperlipoproteinemic patients. Gradient polyacrylamide gel electrophoresis revealed a decrease in small LDL particles. Bezafibrate did not affect the plasma level of HDL2-TC but reduced the HDL2-TG concentration significantly (P < 0.001). Bezafibrate increased the plasma level of HDL3-TC by 37% and reduced the HDL3-TG level significantly by 20% (P < 0.001). Gradient polyacrylamide gel electrophoresis revealed an increase in HDL3a and a decrease in HDL2a. Bezafibrate suppressed the activities of LCAT and CETP by 21% (P < 0.001) and 17% (P < 0.01), respectively. The bezafibrate-induced decrease in plasma levels of small, heavy LDL might be related to its inhibition of LCAT and CETP activities which resulted in suppression of heteroexchange of HDL-EC with triglyceride in large, light LDL. The bezafibrate-induced increase in large HDL3 (HDL3a) could not be explained solely by its suppression of LCAT and CETP activities. The decrease of plasma small, heavy LDL as well as TG-rich lipoproteins by bezafibrate seems to be beneficial for prevention of atherosclerotic diseases.

Adult↗

PubMed1987

Bezafibrate. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hyperlipidaemia.

Bezafibrate is a lipid-lowering drug, chemically related to clofibrate. At its recommended dosage of 200 mg 3 times daily, or alternatively 400 mg once daily as a sustained-release preparation, it produces substantial reductions in plasma triglyceride and cholesterol concentrations in patients with hypertriglyceridaemia and hypercholesterolaemia, respectively. Preliminary investigations indicate that a single daily dose of 400 mg in a sustained-release preparation is as effective as 200 mg 3 times daily. In patients with any type of hyperlipoproteinaemia bezafibrate also increases the plasma HDL-cholesterol concentration. These effects are equivalent in patients with primary hyperlipoproteinaemia or hyperlipoproteinaemia secondary to diabetes or renal disease, although dosage adjustment is important in the latter group. During long term therapy (2 to 4 years) the influence of bezafibrate on the lipid profile is sustained. The lipid-lowering effects of bezafibrate are at least equivalent to those of clofibrate, fenofibrate, colestipol, probucol or sustained release etofibrate. In addition, the increase in HDL-cholesterol tends to be at least as great as with all alternative treatments studied. Bezafibrate is rapidly eliminated, and thus does not accumulate during prolonged administration in patients with normal renal function. Experimental studies have shown bezafibrate to have a complex range of effects on lipoproteins and on the enzymes and receptors involved in lipid metabolism. However, its exact mechanism of lipid-lowering action is unclear. Bezafibrate enhances anticoagulation in hyperlipoproteinaemic patients requiring anticoagulant therapy, and preliminary investigations indicate that it reduces the plasma fibrinogen concentration, especially in patients with hyperfibrinogenaemia. These properties of bezafibrate could contribute to an antiatherogenic effect of the drug, but further investigation is required to establish the drug's potential as chronic therapy in patients with hyperfibrinogenaemic atherosclerosis. Adverse reactions to bezafibrate have largely been restricted to gastrointestinal disturbances, with some cutaneous reactions and central nervous system effects. The incidence of side effects has been no greater than with comparative lipid-lowering drugs. In patients with renal disease, a few cases of marked elevation of serum creatine phosphokinase and myoglobin, and associated muscle cramps, have been reported (diagnosed as rhabdomyolysis). Hepatic enzyme induction by bezafibrate in rats results in hepatomegaly, but there has been no case of significant hepatotoxicity in man.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1996

Angiographic assessment of effects of bezafibrate on progression of coronary artery disease in young male postinfarction patients.

BACKGROUND: Bezafibrate has effects on lipid metabolism and haemostatic function. We undertook a double-blind, placebo-controlled intervention trial, the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT), to establish whether bezafibrate (200 mg three times daily) could retard or prevent the progression of atherosclerotic lesions in dyslipidaemic male survivors of myocardial infarction who were younger than 45 years at the time of the event. METHODS: 92 patients completed an initial 3-month period of dietary intervention and were randomly assigned to treatment with bezafibrate or placebo. Dietary intervention continued throughout the trial. Coronary angiography was done at baseline and after 2 and 5 years. 81 patients (42 bezafibrate treated and 39 placebo treated) who underwent baseline angiography and at least one post-treatment angiogram were included in the efficacy analysis. The primary endpoint was change in mean minimum lumen diameter. FINDINGS: The mean minimum lumen diameter decreased from baseline to the last angiographic assessment (2 or 5 years) by 0.06 mm (95% CI 0.15 reduction to 0.01 increase) in the bezafibrate group and by 0.17 mm (0.33 reduction to 0.09 increase) in the placebo group. The treatment effect was therefore 0.13 mm (95% CI 0.10 to 0.15; p=0.049). Parallel treatment effects, although not statistically significant, were observed for the secondary angiographic endpoints (mean segment diameter 0.02 mm [0.01-0.04] and percentage stenosis -3.41% [-4.00 to -2.98]). The cumulative coronary event rate was significantly lower among bezafibrate-treated than among placebo-treated patients (three vs 11 patients; p=0.02). There were significant treatment effects of bezafibrate for serum concentrations of cholesterol (-9%; p<0.001), very-low-density-lipoprotein (VLDL) cholesterol (-35%; p<0.001), serum triglycerides (-31%; p<0.001), VLDL triglycerides (-37%; p<0.001), and plasma fibrinogen (-12%; p=0.001), whereas low-density (LDL) cholesterol concentrations did not change. High density lipoprotein (HDL) cholesterol increased significantly with bezafibrate (9%; p=0.02). INTERPRETATION: The results show that bezfibrate improves dyslipidaemia, lowers plasma fibrinogen, slows the progression of focal coronary atherosclerosis, and reduces coronary events in young survivors of myocardial infarction.

Adult↗

PubMed1996

Chemoprevention of radiation-induced mammary tumors in rats by bezafibrate administered together with diethylstilbestrol as a promoter.

Pregnant Wistar-MS strain rats were irradiated with 2.6 Gy of gamma-rays at day 20 of pregnancy. Rats in the control group (n = 48) were then implanted with a diethylstilbestrol (DES) pellet at 35 days after weaning, while being fed a control (MB-1) diet. The incidence of mammary tumors was 89.6% within 1 year. In the experimental group (n = 22), a bezafibrate (0.15%) diet was initiated immediately after weaning, and 35 days after weaning a DES pellet was implanted. Administration of dietary bezafibrate together with DES-implantation continued for a period of 1 year, at which time the experiment was terminated. The incidence (27.3%) of the mammary tumors in the bezafibrate-fed rats was less than one-third of that in the control rats. Compared with the control group, the number of mammary tumors per tumor-bearing rat in the bezafibrate-treated group was reduced. For clarification of the mechanism of the chemopreventive effects of bezafibrate, lipid and hormone concentrations in serum were measured. Bezafibrate-fed rats showed a significant decrease in serum prolactin (56%) and triglyceride (63%) concentrations, and a significant increase in serum estradiol-17beta (3.8-fold), cholesterol ester (2.0-fold) and TSH (2.0-fold) concentrations in comparison with the control rats. The bezafibrate diet inhibited the formation of DES-induced pituitary tumors. However, the development of mammary glands in the bezafibrate-fed rats was stimulated more than that in the control rats treated with DES alone. The present results demonstrate that bezafibrate is effective in preventing mammary tumors induced by radiation together with DES, possibly by reducing prolactin and triglyceride concentrations.

Animals↗

PubMed1995

Atherogenic risk reduction in patients with dyslipidaemia. comparison between bezafibrate and lovastatin.

OBJECTIVE: To examine the atherogenic risk-reducing effect of bezafibrate and lovastatin. DESIGN, SETTING, PATIENTS, INTERVENTIONS: Double-blind, randomized clinical trial of male and female patients with moderate hypercholesterolaemia with or without hypertriglyceridaemia. Two months dietary treatment followed by 400 mg sustained release bezafibrate every day or 20 mg lovastatin every day for 6 months. Patients recruited (n = 561) and treated (n = 524) by primary care physicians throughout Austria. MAIN OUTCOME MEASURES: Multifactorial assessment of atherogenic risk profile. RESULTS: Bezafibrate increased high density lipoprotein cholesterol by 16%, lovastatin by 10% (P < 0.05). Bezafibrate decreased low density lipoprotein cholesterol by 20%, lovastatin by 27% (P < 0.001). Bezafibrate decreased total cholesterol by 15%, lovastatin by 18% (P < 0.001). Bezafibrate reduced triglycerides by 29%, lovastatin by 13% (P < 0.001); and fibrinogen by 9.4% and 3.0%, respectively. Fibrinogen reduction as a result of bezafibrate administration was dependent on starting levels. The risk ratio cholesterol:high density lipoprotein cholesterol (baseline both 6.1) reduction was 27% in both groups. The low:high density lipoprotein ratio (baseline: 4.1/4.2) reduction reached 31% and 34% respectively. Coronary events' probability (calculated from multifactorial risk functions) were greatly reduced by both agents (41%/33%). Hypertriglyceridaemic patients had a higher initial global coronary risk and profited more from treatment. Bezafibrate was significantly better tolerated (P < 0.001) than lovastatin; most events were gastrointestinal (6 vs 14, ns) or as a result of creatine phosphokinase elevations (3 vs 12, P < 0.05). CONCLUSIONS: Both treatments significantly reduced the risk parameters for developing coronary heart disease, and calculated multifactorial coronary risk was similarly decreased. When selecting a drug for moderate dyslipidaemia and if haemostatic regulation is disturbed, the additional effect of bezafibrate on elevated fibrinogen levels should be considered.

Adult↗

PubMed1980

[Comparative double-blind investigation of bezafibrate and clofibrate in patients with primary hyperlipoproteinaemia].

The lipid-reducing effects of bezafibrate and clofibrate were investigated in a double-blind crossover trial. 3 x 200 mg/d bezafibrate and 3 x 500 mg/d clofibrate were administered for periods of 8 weeks each to 22 patients with primary hyperlipoproteinaemia (9 Type IIb, 13 Type IV). Placebo periods preceded and followed the periods of medication. Compliance was checked by determination of the serum concentrations of bezafibrate and clofibrate. As compared with the pre-therapy value under placebo, cholesterol was reduced by 14% with bezafibrate and 7% with clofibrate in the group as a whole. In Type IIb patients cholesterol was reduced by 16% with bezafibrate as against 10% with clofibrate, and in Type IV patients by 12% with bezafibrate and 6% with clofibrate. A similar response was found in triglyceride reduction: 36% vs. 18% for the group as a whole; 47% vs. 31% for Type IIb; and 29% vs. 9% for Type IV. The difference in triglyceride reduction for the group as a whole was significant at the p less than 0.05 level. Body weight, pulse rate, and blood pressure showed no changes during the entire period of investigation. Fasting blood glucose was somewhat lower under both substances than under the subsequent placebo period while urea-N and creatinine was increased for both as compared with both pre- and post-therapy placebo periods. Under bezafibrate there was an increase in CPK as compared with the second placebo phase. There were no changes in GOT and GPT. Reductions in gamma-GT, alkaline phosphatase, and bilirubin were observed under both bezafibrate and clofibrate, as were slight decreases in haemoglobin, erythrocytes, and leucocytes, and a small increase in thrombocytes. No changes in urinary excretion of protein or glucose were observed. No subjective side effects were reported, either for bezafibrate or for clofibrate.

Bezafibrate↗

PubMed1978

[Comparison of clofibrate and bezafibrate in type IIa and type IIb hyperlipoproteinemia].

In a randomized block-trial the comparative efficacy and side-effects of clofibrate (2 X 1 g), placebo and bezafibrate (3 X 150 mg) were tested in groups of 24 patients each with hyperlipoproteinemia type IIa and IIb. Each period of treatment was 2 months. Both bezafibrate and clofibrate as compared to placebo were associated with a significant lowering of triglycerides and cholesterol: triglycerides by 30% in type IIa and a 41% reduction in type IIb, whereas clofibrate lowered triglycerides by 23% in type IIa and 28% in type IIb. Bezafibrate reduced total cholesterol by 18% in type IIa and 12% in type IIb as opposed to clofibrate reducing cholesterol by 16% in type IIa and 8% in type IIb. Bezafibrate compared to clofibrate was shown to be significantly more effective in lowering triglycerides in type IIa correlating to a significant reduction of VLDL- and LDL-triglycerides in this type. Both substances significantly lowered LDL-cholesterol in type IIa; in type IIb only bezafibrate was effective. HDL-cholesterol increased significantly with bezafibrate. The effect of clofibrate raising LDL-cholesterol in dependence on the initial concentration of the VLDL-triglycerides was seen less frequently after bezafibrate and only with higher initial VLDL-concentrations as compared to clofibrate. Patients tolerated both bezafibrate and clofibrate equally well. It should be considered that bezafibrate was not given in the optimal dose of 3 X 200 mg.

Adult↗

PubMed1989

Effects of bezafibrate on insulin secretion and peripheral insulin sensitivity in hyperlipidemic patients with and without diabetes.

Although it has been reported that bezafibrate influences carbohydrate metabolism, this possibility has never been properly evaluated in a controlled clinical trial. In this study we attempted to evaluate the effects of bezafibrate on plasma lipoproteins, glucose tolerance, insulin secretion and peripheral insulin sensitivity in a group of hypertriglyceridemic patients with and without diabetes. Sixteen hyperlipidemic patients (10 males and 6 females) participated in the study. Eight had type IIB and 8 type IV hyperlipoproteinemia; 6 of them also had non-insulin dependent diabetes mellitus. The study was performed according to a double blind, crossover design: after 1 month wash-out period in which patients were on diet alone, they underwent, in a random order, a period of placebo therapy and another period in which they received a single daily dose of a long-acting bezafibrate preparation (400 mg) administered in the evening. Each treatment lasted 2 months. Total plasma and VLDL triglyceride concentrations were consistently reduced by bezafibrate (-46%, P less than 0.001; and -50%, P less than 0.001). Total and VLDL-cholesterol were also reduced by bezafibrate. The effects of bezafibrate on lipoproteins were similar in diabetic and non-diabetic subjects. Bezafibrate treatment did not influence fasting blood glucose concentration, glucose tolerance, peripheral insulin sensitivity or insulin secretion. In conclusion, the results of this controlled trial clearly indicate that bezafibrate can be successfully employed to lower plasma lipid levels in patients with non-insulin dependent diabetes mellitus and hyperlipidemia.

Adult↗

PubMed1996

Secondary preventive potential of lipid-lowering drugs. The Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT).

Current experience from coronary angiographic trials using different treatment regimens such as lifestyle changes, resins, nicotinic acid and statins, shows that progression of atheroma can be retarded, and that regression can sometimes be induced, by a marked lowering of LDL-cholesterol. Young post-myocardial infarction patients, however, usually exhibit a multiplicity of metabolic risk factors with dyslipidaemias, predominantly hypertriglyceridaemia, and disturbances of glucose-insulin homeostasis and of the haemostatic system. These factors, together coupled with coronary angiographic data showing that the degree of dyslipidaemia is related to the extent and degree of coronary atherosclerosis, and the fact that rapid progression of coronary atherosclerosis was foreseen in this group of patients, resulted in the initiation of the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) in 1985. BECAIT was a 5-year, double-blind, placebo-controlled study of bezafibrate (200 mg three times daily) and dietary intervention in dyslipidaemic male survivors of myocardial infarction below 45 years of age. The angiographic analysis included 81 patients (42 bezafibrate and 39 placebo) who underwent baseline and at least one post-treatment angiogram, at 2 and 5 years. Changes in mean minimum lumen diameter indicated that there was 0.13 mm less (95% Cl: 0.10; 0.15) disease progression in focal lesions in the bezafibrate group than in the placebo group (P = 0.049). Parallel, but non-statistically significant, treatment effects were observed for mean segment diameter and percent stenosis. Three patients treated with bezafibrate and 11 patients in the placebo group suffered coronary events during the course of the trial (P = 0.02 logrank test). The angiographic effects of bezafibrate were accompanied by statistically significant reductions in serum cholesterol and triglycerides. Furthermore, plasma fibrinogen levels were significantly reduced and HDL-cholesterol concentration increased but there was no net change in LDL-cholesterol. These findings show that bezafibrate slowed the progression of focal coronary atherosclerosis to a degree that is comparable to that achieved with the statins in angiographic trials such as MAAS and REGRESS. Bezafibrate also reduced the occurrence of coronary events in young post-infarction victims. Like BECAIT, analyses of data from the NHLBI type II study, CLAS, POSCH and MARS provide evidence for the role of triglyceride-rich lipoproteins in the progression of coronary artery disease. Retardation of progression of atherosclerosis and a reduction in coronary events is, therefore, possible without reducing LDL-cholesterol.

Adult↗

PubMed1996

Effects of bezafibrate on erythrocyte membrane phospholipids in alcohol-treated rats.

Male rats of the Wistar strain were divided 4 groups, and give a liquid diet of control feed, bezafibrate (150 mg/kg), ethanol, and ethanol plus bezafibrate for 5 week. The effect of bezafibrate supplementation on rats fed ethanol was examined in terms of the fatty acid composition of the phospholipids in the erythrocyte membrane. In the phospholipids profiles of erythrocyte membranes, PI was significantly decreased. The decrease in PI caused by bezafibrate appeared to substantially affect the membrane and consequently lead to changes in the membrane anchor. In the fatty acid composition of the PC, C20: 4 was significantly decreased in the group receiving alcohol (p < 0.05) but increased in the groups receiving bezafibrate (p < 0.05). In the fatty acid composition of the PE, C16: 0 was significantly increased in the three groups when compared with the control, and C20: 4 was decreased in the alcohol group (p < 0.05). In the fatty acid of SM and PI, C20: 4 was decreased and C18: 0 increased in the alcohol group. In the PS, C14: 0 was increased in the alcohol group, and decreased in the alcohol plus bezafibrate group (p < 0.01). The levels of arachidonic acid in the total fatty acids that constituted the membrane phospholipids were decreased in the rats given ethanol (p < 0.05). However, arachidonic acid in the group of bezafibrate supplementation on rats fed ethanol were elevated in comparison with the alcohol group (p < 0.05). With decreasing arachidonic acid as a marker of alcohol tissue injury following chronic alcohol intake, the effects of bezafibrate supplementation appear to contribute to membrane fluidity by altering the biochemical flexibility of the membrane.

Alcohol Drinking↗

PubMed1980

Steady-state kinetics of bezafibrate and clofibrate in healthy female volunteers.

The steady-state kinetics of chlorophenoxyisobuytric acid (CPIB) and of bezafibrate were investigated in a strictly controlled, randomised cross-over study in 10 female volunteers, after the conventional oral doses of clofibrate 0.5 g and bezafibrate f0.2 g at 8-h intervals. The mean steady-state concentration of CPIB in serum was 34 times higher than that of bezafibrate, which was due to the considerable cumulation of CPIB, whereas no cumulation of bezafibrate was observed. This is supported by comparison of the AUCs, and of the maximum and mean concentrations of bezafibrate after the first and last doses. beta (0.44 and 0.49 h(-1)) and the half-lives (1.6 and 1.4h) were almost identical after the first and last doses of bezafibrate. The median total clearances of CPIB and bezafibrate amounted to 10.5 and 142.5ml/min, respectively, if complete absorption of both drugs is assumed. Since the apparent volumes of distribution were in the same range for both drugs, the amount of drug present in the organism in steady-state also differed by a factor of approximately 30 under the usual dosage regimen.

Administration, Oral↗

PubMed1988

Simvastatin and bezafibrate: effects on serum lipoproteins and lecithin: cholesterol acyltransferase activity in familial hypercholesterolaemia.

Sixteen subjects with familial hypercholesterolaemia were randomly assigned to treatment with simvastatin 20-40 mg/day (an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase) or with bezafibrate 600 mg/day (a clofibrate analogue) for 12 weeks. Both drugs produced significant reductions in serum and LDL cholesterol; mean percentage fall -30.5% and -38.1% (simvastatin) and -17.8% and -20.6% (bezafibrate), respectively. Both drugs also caused a decrease in VLDL cholesterol, while only bezafibrate decreased the serum and VLDL triglyceride levels and increased HDL cholesterol and serum apolipoprotein A-I and A-II levels. Serum apolipoprotein B fell by 33.3% (simvastatin) and 15.7% (bezafibrate). Simvastatin and bezafibrate produced significant increases in the mean fractional esterification rate of LCAT, by +124.1% and +20.6%, respectively. Thus simvastatin was clearly more effective than bezafibrate in lowering LDL by enhancing its turnover, but bezafibrate had specific effects on VLDL and HDL that might be favourable in combined treatment regimens.

Adult↗

PubMed1992

Double-blind comparison of bezafibrate versus placebo in male volunteers with hyperlipoproteinemia.

The efficacy and safety of bezafibrate were evaluated in 83 patients with type IIa, IIb, or IV hyperlipoproteinemia. Following a 12- to 14-week placebo period on a coronary-prudent diet (Period 1), patients were assigned randomly to receive either bezafibrate 600 mg/day or placebo, plus diet in a double-blind, 12-week treatment period (Period 2). The return of lipid and lipoprotein levels toward baseline was evaluated in a subsequent 8-week period on placebo plus diet (Period 3). In patients with type IIa hyperlipoproteinemia, bezafibrate significantly lowered total (14.6%, P less than 0.001) and LDL-cholesterol (16.4%, P less than 0.001) and total (29.9%, P less than 0.001) and VLDL-triglyceride (44.0%, P less than 0.001) and significantly increased HDL cholesterol (9.5%, P less than 0.001). In patients with type IIb, bezafibrate had a qualitatively similar effect to that seen in type IIa on each of these lipoproteins, but the sample size was too small for statistical evaluation. In patients with type IV, bezafibrate lowered total (48.3%, P less than 0.01) and VLDL-triglyceride (57.7%, P less than 0.001) and VLDL-cholesterol (56.8%, P less than 0.001) and increased HDL-cholesterol (16.6%, P less than 0.05). All values returned toward baseline during Period 3. Only two bezafibrate patients experienced adverse events that were considered definitely treatment related; one was dropped from the study because of elevations in SGOT and SGPT, 1.5- and 4-times the upper limit of normal, respectively. For other laboratory parameters, trends upward or downward were small and of doubtful clinical significance. Bezafibrate appears to be effective and safe for modifying lipid and lipoprotein levels in patients with types IIa, IIb and IV hyperlipoproteinemia.

Adolescent↗

PubMed1989

Effect of combined therapy with bezafibrate and cholestyramine on low-density lipoprotein metabolism in type IIa hypercholesterolemia.

This study was designed to examine the influence of combined therapy with bezafibrate and cholestyramine on plasma lipids and on the metabolism of low-density lipoprotein (LDL). Twenty-one type II hyperlipidemic subjects were treated with bezafibrate alone or in combination with cholestyramine. A 17% fall in plasma cholesterol was seen with bezafibrate, and addition of cholestyramine produced an additional 9% reduction in this lipid. The effectiveness of the combination therapy was mediated through a 47% decrement in very-low-density lipoprotein (VLDL) cholesterol, a 37% reduction in LDL cholesterol, and a 15% increase in the level of that lipid in high-density lipoprotein (HDL). Plasma triglyceride fell 43% when bezafibrate was given alone, and did not change further when cholestyramine was added. The metabolism of LDL was examined in nine individuals to determine the mechanism underlying these changes. No significant modification in LDL synthetic rate was incurred with either drug regimen, whereas the fractional catabolic rate of LDL via the receptor pathway rose by 66% with bezafibrate alone and by 79% (compared to baseline) following the addition of cholestyramine. Plasma HDL rose during bezafibrate therapy due to an increase in the HDL3 subfraction. Compositional analysis of LDL showed a reduction in cholesterol ester and an increase in triglyceride and phospholipid during combined drug therapy. These results demonstrate that combined therapy with bezafibrate and cholestyramine markedly improves the lipoprotein profile in type II hyperlipidemia. The drugs appear to be complementary in their actions upon the LDL receptor pathway.

Adult↗