Disease relevance of Apo-Gemfibrozil

• The results are in accord with two previous trials with different pharmacologic agents and indicate that modification of lipoprotein levels with gemfibrozil reduces the incidence of coronary heart disease in men with dyslipidemia [1].
• Mechanisms for the hypolipidemic action of gemfibrozil were examined in seven patients with hypertriglyceridemia [2].
• MAIN OUTCOME MEASURE: Relation of lipid levels at baseline and averaged during the first 18 months of gemfibrozil treatment with the combined incidence of nonfatal myocardial infarction and CHD death [3].
• Treatment with fat restriction, weight loss, and gemfibrozil was continued after hospitalization [4].
• CONCLUSIONS: Although gemfibrozil with either colestipol or lovastatin favorably altered lipoprotein levels in patients with hypertriglyceridemia and familial combined hyperlipidemia, the combination of gemfibrozil and lovastatin appeared superior overall [5].

Psychiatry related information on Apo-Gemfibrozil

• In mice, gemfibrozil did not significantly increase the frequency or the mean latency period of tumors [6].
• Gemfibrozil was effective in persons with diabetes (risk reduction for composite end point, 32%; P =.004) [7].
• Treatment of hyperlipidemia in renal transplant patients with gemfibrozil and dietary modification [8].
• SETTING: A prospective, multicentre, placebo-controlled, double-blind CHD primary prevention trial with gemfibrozil in primary (occupational) health care units, the Helsinki Heart Study. SUBJECTS: Dyslipidaemic middle-aged men with available alcohol consumption data (1924 of 2035) in the placebo arm of the 5-year study [9].
• The pharmacodynamic effects of zopiclone, measured using psychometric tests, were not affected by gemfibrozil [10].

High impact information on Apo-Gemfibrozil

• METHODS: We conducted a double-blind trial comparing gemfibrozil (1200 mg per day) with placebo in 2531 men with coronary heart disease, an HDL cholesterol level of 40 mg per deciliter (1.0 mmol per liter) or less, and an LDL cholesterol level of 140 mg per deciliter (3.6 mmol per liter) or less [11].
• Medications such as the fibrate gemfibrozil alter statin metabolism and increase statin plasma concentration [12].
• Primary hypertriglyceridemia with borderline high cholesterol and elevated apolipoprotein B concentrations. Comparison of gemfibrozil vs lovastatin therapy [13].
• For the first year of marketing of lovastatin, spontaneous reports of myopathy with documentation of creatine kinase level were reviewed for the use of lovastatin, gemfibrozil, and combination therapy [14].
• Gemfibrozil enhances the listeriacidal effects of fluoroquinolone antibiotics in J774 macrophages [15].

Chemical compound and disease context of Apo-Gemfibrozil

• CONCLUSIONS: Gemfibrozil therapy resulted in a significant reduction in the risk of major cardiovascular events in patients with coronary disease whose primary lipid abnormality was a low HDL cholesterol level [11].
• In this study, gemfibrozil and lovastatin were compared for their effects on the overall lipoprotein profile in 13 men with this type of dyslipidemia [13].
• Serum triglyceride concentration has prognostic value, both for assessing coronary heart disease risk and in predicting the effect of gemfibrozil treatment, especially when used in combination with HDL-C and LDL-C [16].
• Oral administration of gemfibrozil and fenofibrate inhibited clinical signs of experimental autoimmune encephalomyelitis [17].
• Two important clinical trials on the effect of gemfibrozil (Veterans Administration-HDL-Cholesterol Intervention Trial) and bezafibrate (Bezafibrate Infarction Prevention Study) have recently been completed in subjects with elevated triglyceride, low HDL and normal or near-normal LDL-cholesterol levels [18].

Biological context of Apo-Gemfibrozil

• Six patients with primary familial endogenous hypertriglyceridemia with fasting chylomicronemia (type V lipoprotein phenotype) with concurrent subnormal HDL cholesterol levels (HDL deficiency) were treated initially by diet and once stabilized, were given gemfibrozil (1,200 mg/d) [19].
• In the bacterial mutagenesis assays, between 100 and 2,500 microgram gemfibrozil/plate failed to induce a significant increase in revertant bacterial colonies [6].
• Recently, the reduction of the coronary heart disease incidence in the Helsinki Heart Study has implicated favorable modulation of endogenous fibrinolysis by gemfibrozil [20].
• Most factors related to insulin-resistance syndrome decrease fibrinolytic capacity, whereas a recent study showed that gemfibrozil improves it and thus may attenuate thrombotic events [21].
• These results implicate protein-DNA interactions at the DRE region in the transcriptional induction of human apoA-I gene expression by gemfibrozil [22].

Anatomical context of Apo-Gemfibrozil

• Whether frequent exposure to peroxisome proliferators represents a hazard to humans is unknown; however, increased cancer risk has not been shown to be associated with long-term therapeutic administration of the hypolipidemic drugs gemfibrozil, fenofibrate, and clofibrate [23].
• Cholestyramine and gemfibrozil have received indications for preventing complications of atherosclerosis, namely, myocardial infarction and coronary artery disease death [24].
• To determine whether pharmacological concentrations of gemfibrozil directly affect PAI-1 synthesis, we characterized its effects on a human hepatoma cell line (Hep G2) in vitro [25].
• Gemfibrozil, a lipid-lowering drug, inhibits the induction of nitric-oxide synthase in human astrocytes [26].
• More importantly, gemfibrozil was shown to shift the cytokine secretion of human T cell lines by inhibiting IFN-gamma and promoting IL-4 secretion [17].

Associations of Apo-Gemfibrozil with other chemical compounds

• Associations between lipoproteins and the progression of coronary and vein-graft atherosclerosis in a controlled trial with gemfibrozil in men with low baseline levels of HDL cholesterol [27].
• To test this hypothesis, the effect of bezafibrate, as well as of clofibric acid and gemfibrozil, on growth, functional and cytochemical characteristics of human leukaemia-derived cell lines HL-60, U-937 and K-562 has been studied in some details [28].
• In the first phase, gemfibrozil alone (600 mg twice daily) was compared with a placebo, and in the second phase a combination of gemfibrozil and lovastatin (20 mg twice daily) was compared with gemfibrozil alone in a randomized, double-blind, placebo-controlled crossover study [29].
• Pravastatin and gemfibrozil increased apolipoprotein A-I comparably (3.3% versus 5.0%, p = NS) [30].
• METHODS: In a randomised crossover study, 12 healthy volunteers received twice daily for 3 days either 600 mg gemfibrozil, 100 mg itraconazole (first dose 200 mg), both gemfibrozil and itraconazole, or placebo [31].

Gene context of Apo-Gemfibrozil

• Recently, we demonstrated that administration of the PPAR-alpha agonists gemfibrozil and fenofibrate, inhibit the clinical signs of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS) [32].
• Plasma CETP activity was also increased during gemfibrozil treatment while in the placebo group it remained unchanged [33].
• With placebo, VLDLR accounted for 41.8% of VLDL in HTG and 49.0% of VLDL in CHLP, reduced to 27.6% and 38.6%, respectively, with gemfibrozil [34].
• Inhibition of CYP2C8-mediated metabolism by gemfibrozil warrants further in vivo exploration [35].
• Gemfibrozil increased LPL and HL activities by 18.2% (P < 0.05) and by 19.6%, respectively [36].

Analytical, diagnostic and therapeutic context of Apo-Gemfibrozil

• The hypolipidemic effects of gemfibrozil in type V hyperlipidemia. A double-blind, crossover study [37].
• We conclude that gemfibrozil is a well-tolerated and effective hypolipidemic agent for the treatment of patients with severe hypertriglyceridemia when used in conjunction with a low-fat diet [37].
• Carcinogen bioassay and mutagenicity studies with the hypolipidemic agent gemfibrozil [6].
• The effect of gemfibrozil was largely confined to overweight subjects: among those with body mass index (BMI) > 26 kg/m2, the net difference in cardiac end points between gemfibrozil and placebo groups was 21 (25 of 1119 versus 46 of 1081), and in those with BMI < or = 26 kg/m2, it was 7 (31 of 927 versus 38 of 954) [21].
• In aortocoronary bypass grafts, 23 subjects (14%) assigned to placebo had new lesions in the follow-up angiogram, compared with 4 subjects (2%) assigned to gemfibrozil (P<.001) [38].

References