Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Bezafibrate”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
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↗
PubMed2004

Multidrug resistance3 is in situ detected in the liver of patients with primary biliary cirrhosis, and induced in human hepatoma cells by bezafibrate.

Bezafibrate has been empirically used for the treatment of primary biliary cirrhosis. Although its clinical efficacy has been demonstrated, the therapeutic mechanism of action of this drug remains unclear. We suggested that multi-drug resistance (MDR) 3 plays an important role as a mediator of bezafibrate. We adopted a human hepatoma cell line to elucidate the up-regulating effect of bezafibrate. To analyze the effects on mRNA, the dose effect was assessed by slot-blot study, the time course by real time PCR, and the subcellular location was determined by in situ hybridization. The results revealed that MDR3 mRNA reached a peak level 12h after the administration of bezafibrate, and dose dependency was observed. We also investigated the interaction of bile acid and bezafibrate. A low dose of chenodeoxycholic acid could become a co-effecter of bezafibrate. In the protein analysis, a precursor protein was induced by bezafibrate. Even in the cell line endogenously expressing MDR3, the expression of the protein was found to be modulated. We identified MDR3 mRNA in the livers of PBC patients using a sensitive in situ hybridization study. The present findings indicate that PBC patients can respond to bezafibrate, and therefore receive clinical benefits from this medication.

Journal Article↗
PubMed2006

Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate.

BACKGROUND: Development of insulin resistance (IR) may be important in the pathogenesis of both metabolic syndrome and type 2 diabetes mellitus. Few data are available regarding the short-term efficacy of the peroxisome proliferator-activated receptor ligand bezafibrate on IR, and its long-term effect is unknown. The present analysis aimed to investigate the effect of bezafibrate on IR in patients with coronary artery disease enrolled in the Bezafibrate Infarction Prevention Study. METHODS: Metabolic and inflammatory parameters were analyzed from stored frozen plasma samples obtained from patients who completed a 2-year, randomized, double-blind, placebo-controlled study. The homeostatic indexes of IR (HOMA-IRs) were calculated according to the homeostasis model of assessment. RESULTS: Both the patients taking bezafibrate (n = 1262) and those taking placebo (n = 1242) displayed similar baseline characteristics. The HOMA-IRs significantly correlated at baseline and during follow-up with glucose (r = 0.35 and 0.31, respectively) and triglycerides (r = 0.16 and 0.19, respectively). In a subgroup of 351 patients with diabetes, HOMA-IR at baseline was 88% higher than in their counterparts with normal glucose levels (P<.001). In the placebo group, during follow-up there was a significant 34.4% rise in HOMA-IR. In contrast, in the bezafibrate group there was only a nonsignificant 6.6% change in HOMA-IR. The intergroup differences in percentage changes of HOMA-IR were in favor of bezafibrate (P<.001). CONCLUSIONS: In patients with coronary artery disease enrolled in our study, as represented by the placebo group, HOMA-IR increased over time. During the 2 years of the follow-up, bezafibrate significantly attenuated this process.

Aged↗
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↗
PubMed1988

Inhibition of hepatic fatty acid oxidation by bezafibrate and bezafibroyl CoA.

The acute effect of the hypolipidemic agent bezafibrate on fatty acid oxidation was studied in rat hepatocytes and mitochondria. Bezafibrate caused a concentration-related inhibition of oleate oxidation in liver cells. In mitochondria bezafibrate inhibited the oxidation of palmitoyl CoA but had no effect on palmitoylcarnitine oxidation, suggesting the site of inhibition was the formation of the carnitine derivative. Bezafibrate and bezafibroyl CoA inhibited the overt carnitine palmitoyltransferase (I) in rat liver mitochondria with comparable potency but with distinct kinetics. The inhibition caused by bezafibrate was not prevented by omission of Mg++-ATP from the assay mixture, indicating activation of bezafibrate to bezafibroyl CoA was not required for inhibition. The data demonstrate that bezafibrate, like several other peroxisome proliferating agents, inhibits mitochondrial fatty acid oxidation in rat liver. The inhibition may be relevant to the mechanism of peroxisome proliferation.

Acyl Coenzyme A↗
PubMed1988

Comparison between simvastatin and bezafibrate in effect on plasma lipoproteins and apolipoproteins in primary hypercholesterolaemia.

The ability of simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, to lower lipid levels in 16 patients with primary hypercholesterolaemia was compared with that of bezafibrate in a 16-week, double-blind, parallel, placebo-controlled trial that was continued in an open crossover fashion. Simvastatin was better than bezafibrate at lowering total and low-density lipoprotein (LDL)-cholesterol and apolipoprotein B concentrations (30.4% [p less than 0.001], 37.3% [p less than 0.001], and 37.8% [p less than 0.001] vs 17.0%, 19.6%, and 24.0%, respectively). Both drugs increased the high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I, but this change was significant only with bezafibrate (p less than 0.05). Bezafibrate and simvastatin reduced triglycerides by 25.6% (p less than 0.001) and 13.7% (p less than 0.05), respectively. Very low-density lipoprotein (VLDL)-cholesterol was significantly reduced only by bezafibrate (44.3%, p less than 0.001). Both drugs were tolerated well and no serious side-effects were noted. The results show that simvastatin was more effective than bezafibrate in lowering total-cholesterol, LDL-cholesterol, and apolipoprotein B, while bezafibrate was better at lowering triglycerides and VLDL-cholesterol and at raising HDL-cholesterol and apolipoprotein A-I.

Adult↗
PubMed2001

Effects of bezafibrate on insulin sensitivity and insulin secretion in non-obese Japanese type 2 diabetic patients.

The aim of the present study was to investigate the effect of bezafibrate on insulin sensitivity and insulin secretion in 30 non-obese Japanese type 2 diabetic patients with hypertriglyceridemia (serum triglycerides > 150 mg/dL). Insulin sensitivity was measured with homeostasis model assessment insulin resistance (HOMA-IR) proposed by Matthews et al. HOMA-B-cell function, proposed by Matthews et al validated against minimal model-derived insulin secretion, was used to assess pancreatic insulin function. Twenty-two patients were treated with glibenclimide and the rest were treated with diet alone. All patients were treated with bezafibrate (400 mg/d) for 3 months. There were no changes in diet and the dose of any medications used throughout the study. Fasting glucose, insulin, triglycerides, HDL cholesterol, and total cholesterol levels were measured before and after treatment of bezafibrate. After treatment of bezafibrate for 3 months, serum triglyceride levels significantly decreased from 277 +/- 30 to 139 +/- 9 mg/dL (P <.001) and serum HDL cholesterol levels increased significantly from 45 +/- 2 to 52 +/- 2 mg/dL (P =.003). Serum cholesterol level was unchanged during the study (198 +/- 7 v 201 +/- 7 mg/dL, P =.383). Fasting glucose (163 +/- 8 v 139 +/- 6 mg/dL, P =.006) significantly decreased after the treatment with bezafibrate. HbA1c levels decreased, although not statistically significant (7.50 +/- 0.25 v 7.17% +/- 0.19%, P =.147). On the other hand, fasting insulin (9.3 +/- 0.7 v 7.3 +/- 0.5 microU/mL, P =.010) and HOMA-IR (3.61 +/- 0.24 to 2.53 +/- 0.20, P <.001) levels decreased significantly after the treatment with bezafibrate. In contrast, HOMA-B-cell function did not change during the study (41.4 +/- 5.5 v 41.8 +/- 4.7, P =.478). There was no significant difference in body mass index (BMI) levels before and after the therapy (23.0 +/- 0.4 v 23.1 +/- 0.4 kg/m(2), P =.483). From these results, it can be concluded that bezafibrate reduces serum triglycerides, insulin resistance, and fasting blood glucose levels in non-obese Japanese type 2 diabetic patients.

Adult↗
PubMed2004

Role of peroxisome proliferator-activated receptor-alpha (PPARalpha) in bezafibrate-induced hepatocarcinogenesis and cholestasis.

Prolonged administration of peroxisome proliferators to rodents typically leads to hepatocarcinogenesis. Peroxisome proliferator-activated receptor-alpha (PPARalpha) is required to mediate alterations in PPARalpha target gene expression, repress apoptosis, enhance replicative DNA synthesis, oxidative stress to DNA and hepatocarcinogenesis induced by the relatively specific PPARalpha agonist, Wy-14,643. Interestingly, administration of the less specific PPARalpha agonist, bezafibrate, leads to a modest induction of PPARalpha target genes in the absence of PPARalpha expression. In these studies, the role of PPARalpha in modulating hepatocarcinogenesis induced by long-term feeding of 0.5% bezafibrate was examined in wild-type (+/+) and PPARalpha-null (-/-) mice. The average liver weight was significantly higher in (+/+) and (-/-) mice fed bezafibrate than controls, but this effect was considerably less in (-/-) mice as compared with similarly treated (+/+) mice. Increased levels of mRNA encoding cell cycle regulatory proteins and DNA repair enzymes were found in (+/+) mice fed bezafibrate, and this effect was not found in (-/-) mice. In mice fed bezafibrate for 1 year, preneoplastic foci, adenomas and a hepatocellular carcinoma were found in (+/+) mice, while only a single microscopic adenoma was found in one (-/-) mouse. This effect was observed in both Sv/129 and C57BL/6N strains of mice, although only preneoplastic foci were observed in the latter strain. Interestingly, hepatic cholestasis was observed in 100% of the bezafibrate-fed (-/-) mice, and this was accompanied by significantly elevated hepatic expression of mRNA encoding bile salt export pump and lower expression of mRNA encoding cytochrome P450 7A1, consistent with enhanced activation of the bile acid receptor, farnesoid X receptor. Results from these studies demonstrate that the PPARalpha is required to mediate hepatocarcinogenesis induced by bezafibrate, and that PPARalpha protects against potential cholestasis.

Acyl-CoA Oxidase↗
PubMed2003

Bezafibrate, a peroxisome proliferator-activated receptor (PPAR)-alpha activator, prevents pancreatic degeneration in obese and diabetic rats.

INTRODUCTION: Damage to the exocrine pancreas has been observed in patients and animals with hyperlipidemia and hyperglycemia. Bezafibrate, a peroxisome proliferator-activated receptor (PPAR)-alpha activator, has been shown to improve lipid and glucose metabolism, and to interfere with the inflammatory response. AIM: To examine the effects of bezafibrate on exocrine pancreas in hyperlipidemic obese and diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats that have no cholecystokinin-1 receptor gene expression. METHODOLOGY: One group of rats (n = 8) received a bezafibrate-rich diet (150 mg/100 g normal chow) from 12 weeks of age until 30 weeks of age, whereas a control group (n = 8) received standard rat chow. RESULTS: Bezafibrate treatment significantly reduced serum triglyceride, total cholesterol, and free fatty acids levels and significantly increased the pancreatic wet weight (1,145 +/- 54 vs 874 +/- 33 mg/rat, p < 0.01), and protein (169 +/- 7 vs 128 +/- 11 mg/pancreas p < 0.01) and enzyme contents in the pancreas compared with those in untreated control rats. Immunohistochemical studies of the pancreas showed that expression of proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1beta and interleukin-6, and alpha-smooth muscle actin in bezafibrate-treated rats was greatly suppressed compared with that in the untreated control rats. The histopathologic changes such as vacuolar degeneration and tubular complexes observed in the control rat pancreas were markedly improved in bezafibrate-treated rats. CONCLUSIONS: Our results suggest that bezafibrate reduces hyperlipidemia, inhibits pancreatic inflammation, and prevents pancreatic degeneration in obese and diabetic OLETF rats.

Actins↗
PubMed2004

Effects of pravastatin and bezafibrate on biliary lipid excretion and hepatic expression of Abcg5 and Abcg8 in the rat.

BACKGROUND AND AIM: Multidrug resistance associated gene product 2 (Mdr2) is believed to have a significant role in biliary cholesterol and phospholipid secretions. Both pravastatin and bezafibrate resulted in Mdr2 induction, but increased cholesterol secretion was observed only in pravastatin treatment. To explore the mechanism, the hepatic expression of genes that are responsible for the metabolism of the lipids was studied. METHODS: Rats were divided into three experimental groups: (i) the control group; (ii) the bezafibrate group, which was fed a diet containing 0.45% bezafibrate for 5 days; and (iii) the pravastatin group, which was fed a diet containing 0.1% pravastatin for 5 days. Serum, hepatic and biliary lipids were measured by colorimetric assays and hepatic mRNA related to lipid metabolism was studied by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In the bezafibrate group biliary phospholipid secretion was increased although cholesterol secretion was not increased. In the pravastatin group, biliary cholesterol and phospholipid secretions were significantly increased. The biliary cholesterol/phospholipid ratio was decreased in the bezafibrate group, but the ratio did not change in the pravastatin group. Hepatic Mdr2, Abcg5 and Abcg8 mRNA expression was remarkably increased in the pravastatin group in comparison with the control group (184%, 264% and 247% of control value, respectively). In the bezafibrate group the hepatic gene expression of Mdr2 was increased (157% of control value), but there were no significant changes in hepatic Abcg5 and Abcg8 mRNA expression compared with the control group. CONCLUSIONS: Compared with Mdr2, Abcg5 and Abcg8 seem to be more essential transporters for biliary secretion of cholesterol. Pravastatin upregulated Abcg5/Abcg8 while bezafibrate did not, which appears to explain the different effects of these compounds on biliary lipid secretion.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1996

Effects of bezafibrate on ethanol oxidation in rats.

Bezafibrate is used to lower serum lipid levels in humans. Fibrate derivatives induce an enzyme participating in the beta-oxidation by peroxisomes. We gave ethanol (2 g/kg) orally to bezafibrate-treated (300 mg/kg) male rats of the Wistar strain. Blood ethanol levels were remarkably lower and ethanol elimination stood at 432.6 mg/kg/hr (control, 336.6 mg/kg/hr) in the bezafibrate group (p < 0.01). Blood acetate levels were conversely higher in the bezafibrate group. The fatty acid beta-oxidation activity of liver peroxisome in bezafibrate-treated, clofibrate-treated, or gamma-linolenic acid-treated rats for 4 days was assayed. The activity was 5.8-fold higher in rats given bezafibrate, 5.4-fold in the clofibrate (p < 0.01), and 2.0-fold in the gamma-linolenic acid (p < 0.05). Alcohol dehydrogenase and aldehyde dehydrogenase activity of cytosol in the liver was not induced by the hypolipidemic drugs, but aldehyde dehydrogenase activity in the liver homogenate was induced. From foregoing results, bezafibrate induced in the organism beta-oxidation by peroxisomes and increased H2O2 production, which led to augmented ethanol metabolism by catalase.

Acetates↗
PubMed2003

Gall bladder dysmotility: a risk factor for gall stone formation in hypertriglyceridaemia and reversal on triglyceride lowering therapy by bezafibrate and fish oil.

BACKGROUND AND AIM: The aim of this study was to unravel the mechanisms responsible for the increased risk of gall stone disease in hypertriglyceridaemia (HTG) and to compare the effects of triglyceride lowering therapy by bezafibrate and fish oil on determinants of cholelithiasis (biliary lipid composition and gall bladder motility) in HTG patients. PATIENTS AND METHODS: Gall bladder motility (ultrasonography) was studied postprandially and during infusion of cholecystokinin (CCK). Determinants of cholelithiasis and serum lipids were compared between nine HTG patients and 10 age, sex, and body mass index matched normolipidaemic controls. The effects of bezafibrate and fish oil in HTG patients were studied in a randomised cross over trial. RESULTS: HTG patients showed 14-fold higher serum triglyceride (TG) levels than controls. Biliary lipid composition, fasting gall bladder volumes, and CCK levels did not differ between HTG patients and controls. Gall bladder emptying was reduced in HTG patients compared with controls during CCK infusion (-22%) as well as in response to a meal (-37%; both p<0.001). Postprandial CCK levels were significantly higher in HTG patients. Both bezafibrate and fish oil reduced serum TG levels (-68% and -51% v baseline, respectively; both p<0.01). Fasting CCK levels were not affected whereas CCK induced gall bladder emptying increased during bezafibrate (+29%; p<0.001) and tended to increase on fish oil therapy (+13%; p=0.07). Postprandial gall bladder motility improved on bezafibrate and fish oil (+47 and +25% v baseline, respectively; both p<0.02) at least partly due to increased gall bladder sensitivity to CCK (both p<0.05 v baseline). Bezafibrate but not fish oil increased the molar ratio of cholesterol to bile acids (+40%; p</=0.05) but no effects on cholesterol saturation index were seen with either treatment. CONCLUSIONS: We suggest that impaired gall bladder motility occurs in HTG patients due to decreased sensitivity to CCK, which may add to the enhanced risk of gall stone disease in HTG patients. Triglyceride lowering therapy by both fish oil and bezafibrate improve gall bladder dysmotility without adversely affecting biliary cholesterol saturation.

Analysis of Variance↗
PubMed2004

Peroxisome proliferator-activated receptor ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease.

BACKGROUND: Recent studies have shown that type 2 diabetes is preventable by both lifestyle interventions and medications that influence primary glucose metabolism. Whether pharmacological interventions that influence primary lipid metabolism can also delay development of type 2 diabetes is unknown. The goal of this study was to evaluate the effect of the peroxisome proliferator-activated receptor ligand bezafibrate on the progression of impaired fasting glucose phase to type 2 diabetes in patients with coronary artery disease over a 6.2-year follow-up period. METHODS AND RESULTS: The study sample comprised 303 nondiabetic patients 42 to 74 years of age with a fasting blood glucose level of 110 to 125 mg/dL (6.1 to 6.9 mmol/L). The patients received either 400 mg bezafibrate retard (156 patients) or placebo (147 patients) once a day. No patients were using statins, and use of ACE inhibitors, which also reduce diabetes incidence, was relatively low. During follow-up, development of new-onset diabetes was recorded in 146 patients: in 80 (54.4%) from the placebo group and 66 (42.3%) from the bezafibrate group (P=0.04). The mean time until onset of new diabetes was significantly delayed in patients on bezafibrate compared with patients on placebo: 4.6+/-2.3 versus 3.8+/-2.6 years (P=0.004). Multivariate analysis identified bezafibrate treatment as an independent predictor of reduced risk of new diabetes development (hazard ratio, 0.70; 95% CI, 0.49 to 0.99). Other significant variables associated with future overt type 2 diabetes in patients with impaired fasting glucose were total cholesterol level (hazard ratio, 1.22; 95% CI 1.0 to 1.51) and body mass index (hazard ratio, 1.10; 95% CI, 1.05 to 1.16). CONCLUSIONS: Bezafibrate reduces the incidence and delays the onset of type 2 diabetes in patients with impaired fasting glucose. Whether the combination of bezafibrate with other recommended drugs for secondary prevention (statins and ACE inhibitors) would be as efficacious as suggested by our results remains to be determined.

Aged↗
PubMed1999

Chronic effects of lovastatin and bezafibrate on cortical and medullary hemodynamics in deoxycorticosterone acetate-salt hypertensive mice.

Cholesterol synthesis inhibitors and fibrates both exercise effects that could influence BP and renal function in hypertension. To test this issue, transit-time ultrasound flow probes, implanted optical fibers, and laser-Doppler flowmetry were used for measurements of total and regional renal blood flows in lovastatin (40 mg/kg body wt) and bezafibrate (50 mg/kg body wt) chronically treated deoxycorticosterone acetate (DOCA)-salt hypertensive mice. Total renal blood flow was well autoregulated between 70 and 150 mmHg (approximately 3.5 ml/min per g kidney weight in DOCA-salt mice). Both lovastatin and bezafibrate increased renal blood flow to a range between 4.7 and 5.5 ml/min per g kidney weight. In the renal perfusion pressure ranges investigated, renal vascular resistance increased in lovastin- and bezafibrate-treated DOCA-salt mice, but not as steeply as in vehicle-treated DOCA-salt mice. During a stepwise increase in renal perfusion pressure in lovastatin-treated DOCA-salt mice, medullary blood flow increased up to 130% of baseline values, which was not seen in vehicle- or bezafibrate-treated mice. After extracellular volume expansion with 1% saline, 1 ml over 1 min, total renal blood flow was also higher in lovastatin- or bezafibrate-treated DOCA-salt mice, whereas medullary blood flow increased more steeply in lovastatin-, compared with bezafibrate- or vehicle-treated mice. Systemic BP was significantly decreased in lovastatin-treated DOCA-salt mice compared with vehicle-treated mice. Lovastatin prevented histologic evidence for hemostasis in the medullary circulation of DOCA-salt mice. The results suggest that both lovastatin and bezafibrate diminished DOCA-salt-induced reductions in total renal blood flow. Lovastatin also abolished the perturbed medullary blood flow reactions to increased perfusion pressure or to volume expansion. Finally, lovastatin decreased systemic BP in DOCA-salt mice. These data suggest that cholesterol synthesis inhibition or fibrate treatment improve disturbed renal function in a mouse model of salt-dependent hypertension.

Animals↗
PubMed1997

Improved insulin sensitivity by bezafibrate in rats: relationship to fatty acid composition of skeletal-muscle triglycerides.

We investigated the effect of the lipid-lowering agent, bezafibrate, on insulin sensitivity in a dietary model of insulin resistance. Male Sprague-Dawley rats were divided into four groups: control group, administered a standard diet; high-fructose group, given a 40% fructose diet; high-fructose plus lard group, given a 40% fructose diet with 7% lard; and bezafibrate group, given a 40% fructose plus 7% lard diet with 10 mg x kg-1 x day-1 of oral bezafibrate. Insulin action was assessed after 2 weeks with a steady-state plasma glucose (SSPG) level. The fatty acid (FA) composition of skeletal-muscle triglycerides was also determined. A higher SSPG level (20.9 +/- 0.9 vs. 16.5 +/- 1.1 mmol/l in the control group, P < 0.05) as well as a higher systolic blood pressure (120 +/- 2 vs. 101 +/- 2 mmHg, P < 0.01) was observed in the high-fructose plus lard group, but not in the high-fructose group. These changes were prevented by bezafibrate administration. The FA composition of skeletal-muscle triglycerides demonstrated a higher percentage of saturated and monounsaturated FAs (P < 0.01) and a lower percentage of polyunsaturated FAs (P <0.01) in the high-fructose plus lard group versus the control group. These changes were consistent with differences in the dietary intake of FAs. Bezafibrate virtually normalized the FA composition in the high-fructose plus lard group. The ratio of C20:4 to C20:3, an index of delta5 desaturase activity, was significantly higher in the bezafibrate group versus the high-fructose plus lard group (8.60 +/- 0.76 vs. 2.04 +/- 0.27, P < 0.01). In conclusion, the dietary FA composition was closely related to insulin resistance in rats fed 40% fructose. Bezafibrate increased delta5 desaturase activity. Such action may contribute to the improvement of insulin sensitivity.

Animals↗