Bezafibrat-induzierte Myolyse und Myoglobinurie bei Patienten mit eingeschränkter Nierenfunktion

Summary A muscular syndrome has been described in patients on clofibrate and fenofibrate therapy. The present paper describes four patients with impaired renal function in whom symptoms and signs of skeletal muscle damage developed during treatment with another clofibrinic acid derivative, bezafibrate. The syndrome was characterized by variable degrees of muscular cramps and paresis, excessive elevation of muscle enzymes in serum, myoglobinemia and myoglobinuria. Transient deterioration of renal function was also common. All patients had been overdosed with bezafibrate with regard to their renal function. It is concluded that bezafibrate like other lipid lowering agents of the clofibrate type may induce muscle damage, at least if doses are not adjusted to renal function. Extreme caution is warranted when treating patients with renal impairment with bezafibrate and strict dose adjustment to kidney function is necessary to avoid muscle damage.

     

Plasma type IV collagen and fibronectin concentrations in diabetic patients with microangiopathy.

In diabetes mellitus, thickening of basement membrane in capillaries and small vessels is a well-known finding and important in the progression of diabetic microangiopathy. We evaluated whether the plasma levels of type IV collagen and fibronectin, which are important factors of basement membrane, are related with the presence of diabetic microangiopathy. Plasma type IV collagen and fibronectin levels were measured in 40 healthy controls (Mean +/- SD, age; 50.3 +/- 5.5 yr) and 94 diabetic patients (age; 52.4 +/- 13.5 yr) with and without microvascular complications. The mean plasma levels of type IV collagen (5.3 +/- 2.9 ng/ml) and fibronectin (474.4 +/- 119.4 ug/ml) in diabetic patients were significantly higher (p < 0.01) than in healthy controls (3.7 +/- 1.3 ng/ml and 319 +/- 50.9 ug/ml). The mean plasma level of type IV collagen in diabetic patients with complications (6.6 +/- 3.7 ng/ml) was significantly higher (p < 0.01) than in those without complications (4.3 +/- 1.7 ng/ml) and became higher in more complicated patients. Furthermore, the severity of retinopathy and several indicators of nephropathy such as serum BUN, creatinine and proteinuria were closely associated with plasma type IV collagen level and a significant correlation was found between plasma type IV collagen and creatinine clearance (r = -0.31, p < 0.001). There was no significant difference in plasma fibronectin concentrations, however, between the diabetic patients with complications and those without complications.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of bezafibrate and clofibrate on cholesterol ester metabolism in rabbit peritoneal macrophages stimulated with acetylated low density lipoproteins

Bezafibrate and clofibrate reduce the quantity of esterified cholesterol, decrease the incorporation of 14C-labeled oleic acid into cholesterol ester and inhibit acyl coenzyme A cholesterol acyltransferase activity in rabbit peritoneal macrophages stimulated with acetylated low density lipoprotein. In all cases, the effect of bezafibrate was more marked than that of clofibrate. The activity of lysosomal cholesterol ester hydrolase in these cells was not affected by these drugs. It is suggested that these drugs exert an anti-atherogenic activity not only by their action on serum lipids, but by influencing cellular cholesterol ester metabolism.     

New data on the mechanisms of hypermagnesuria in type I diabetes mellitus.

It has been known for long that renal Mg excretion is increased in patients with type I diabetes mellitus, and that these patients have a Mg deficit. It can be hypothesized, that this deficit might be related to the development of late complications in the diabetic. In recent years it has been shown that the increased renal Mg excretion in patients with type I diabetes is due primarily to an elevated plasma glucose concentration. An increase in plasma glucose concentration from 5 to 12 mmol/l more than doubles renal Mg excretion, if everything else is kept constant. Hyperinsulinism may also contribute to the increased renal Mg excretion. However, since improved metabolic control in patients with type I diabetes reduces the renal Mg loss despite an increase in insulin dosage, hyperinsulinism is probably of minor importance in the aetiology of hypermagnesuria in patients with type I diabetes mellitus, compared with the effect of hyperglyeaemia.     

Stent material surface and glucose activate mononuclear cells of control, type 1 and type 2 diabetes subjects

In stent restenosis (ISR) has been described as an unaccomplished tissue healing and its rate is particularly high in diabetic patients. Evidence has been collected which relates the formation of ISR proteoglycan-rich neointimal tissue to the accumulation and protracted activation of macrophages around the stent metal struts. Here, the in vitro activation of mononuclear cells adhering to stainless steel (a material of choice in stent manufacturing) from control and diabetic (types 1 and 2) subjects was assessed in the presence of different glucose levels. The results showed that cells from the control and type 1 diabetes groups produced significantly higher levels of TGF-beta1 when adhering on stainless steel (p = 0.04 and p = 0.01), but a significant PDGF-BB secretion was observed only in control subjects. When tested at physiological glucose concentration, the effect of the stainless steel on control cells was more pronounced. The present study shows that mononuclear cells adhering onto stainless steel secrete growth factors relevant to ISR. Cells from diabetic subjects seem to secrete relatively higher levels of PDGF under hyperglycaemic conditions regardless of the substrate exposed thus offering an explanation for the higher incidence of restenosis in these patients.     

Effect of combined clofibrate-cholestyramine treatment on serum and tissue cholesterol pools and on cholesterol synthesis in hypercholesterolemic swine.

The effect of clofibrate on whole-body cholesterol synthesis was studied in cholestyramine-treated hypercholesterolemic male Yorkshire swine and swine with normocholesterolemia or mild hypercholesterolemia.Daily whole-body synthesis rates were calculated by methods developed for the non-steady-state condition using various parameters of cholesterol balance; dietary cholesterol intake, fecal excretion of steroids, and cholesterol retention or loss in the body.After 16 days of treatment, the cholestyramine group showed reductions in serum cholesterol level and carcass cholesterol concentration, and increases in fecal steroid excretion and whole-body cholesterol synthesis, as compared with pretreatment values. The group which received both cholestyramine and clofibrate showed the same changes in all parameters listed above, but showed a greater reduction in serum cholesterol levels and greater increases in fecal excretion and whole-body cholesterol synthesis as compared with the group receiving cholestyramine alone.Unfortunately for the therapeutic implications, the increased output of steroids resulting from treatment with the combination of the two drugs was largely offset by a corresponding increase in cholesterol synthesis. The increase in synthesis might have been caused by a direct effect of clofibrate on the biosynthetic process. However, it seemed more likely that the increased synthesis was secondary to the increased output of steroids.The effect of clofibrate alone in hypercholesterolemic swine treated for 64 days revealed restraint in increase of serum cholesterol levels as compared to untreated controls, and an increase in total steroid excretion. No reduction in the whole-body cholesterol synthesis was observed in the clofibrate-treated group.In the other experiment, clofibrate even under mildly hypercholesterolemic or normocholesterolemic conditions did not result in a reduction of whole-body cholesterol synthesis, although serum cholesterol levels were reduced under both conditions.     

Clinical usefulness of measurement of urine type IV collagen for detection of early phase of nephropathy in type 2 diabetic patients

Urine type IV collagen concentrations in type 2 diabetic patients were measured by enzyme immunoassay which has crossreactivity with only intact type IV collagen, and the clinical usefulness for estimating the early phase of diabetic nephropathy was evaluated. Precision of the measurement system was satisfactory for clinical use and the value did not influenced by the presence of sediments in urine. In whole type 2 diabetic patients (N=132), urine type IV collagen concentration (microg/g of creatinine) increased with development of nephropathy and showed significantly increase even in normoalbuminuria when compared with that in normal control subjects (N=117). In type 2 diabetic patients (N=100) with mild microalbuminuria (less than 100 mg/g of creatinine), multiple regression analysis revealed that HbA1C was extracted as a significant valuable for urine type IV collagen, while body mass index was extracted as a significant valuable for urine albumin. In these subjects, urine type IV collagen was significantly lower in the patients with good metabolic control (HbA1C<8.0%) than those with poor control (HbA1> or =8.0%), while the urine albumin was not significantly different between those two groups. These results suggest that measurement of urine type IV collagen in type 2 diabetic patients is useful for detection of early phase of diabetic nephropathy.     

Bone mineral metabolism in human type 1 (insulin dependent) diabetes mellitus

Decreased bone mineral content has been observed in several studies of type 1 (insulin-dependent) diabetics in comparison with age and sex matched control subjects. In type 2 diabetics contradictory results have been obtained, probably related to varying degrees of body overweight in the patients investigated. The decrease in bone mineral content in type 1 diabetics was most pronounced in patients with childhood or adolescent onset of the disease, with ceased beta-cell function, with high insulin dosage, and poor glucose regulation. In a subgroup of patients having all these "risk factors" bone mineral content was decreased some 20%, as compared with patients without any "risk factors", and/or with sex and age matched controls. Bone mineral homeostasis was characterized by increased urinary excretions of bone minerals (calcium, phosphate and magnesium) related to the degree of hyperglycaemia and insulin dosage, by decreased serum concentrations of ionized calcium and magnesium, by increased to normal serum concentrations of phosphate, by a low-normal serum concentration of parathyroid hormone, and by a low-normal serum concentration of 1,25-dihydroxyvitamin D. This indicates a state of functional hypoparathyroidism in type 1 diabetics. Several mechanisms may thus contribute to diabetic osteopenia: Proneness to metabolic acidosis, hypocalcaemia, insulin deficiency and perhaps also hypomagnesaemia and hypoparathyroidism.     

Liver histopathology of the hepatitis A virus infection: a comparison with hepatitis type B and non-a, non-b

Liver biopsies from 86 patients with serologically established acute hepatitis A were evaluated for quantitative and qualitative light microscopic features together with biopsies from 78 patients with acute hepatitis type B and 76 patients with acute hepatitis type non-A, non-B. Hepatitis A was characterised by more pronounced portal inflammation than hepatitis non-A, non-B (p less than 0.01) but less conspicuous parenchymal changes (focal necrosis, Kupffer cell proliferation, acidophil bodies, ballooning) than found in hepatitis type B (p less than 0.01). Steatosis occurred in 10% of the hepatitis A biopsies compared with 26% (p less 0.01) and 6% (not significant) in the hepatitis non-A, non-B and B groups, respectively. A comparison between the histological findings in women and men revealed that iron deposits occurred in more than half of the men compared to less than 20% of the women (p less than 0.01) irrespective of hepatitis type. Histological and biochemical follow-up was available in 36 patients with hepatitis A. For the majority of these patients the bilirubin concentration reached normal values within one month of the initial biopsy. The activity of serum transaminases showed good correlation with the degree of histological resolution. Non-specific reactive hepatitis with slightly raised serum transaminases were often seen during recovery from hepatitis A. These patients may be misinterpreted as cases of acute non-A, non-B hepatitis.     

Role of amylin in the pathogenesis of type II diabetes mellitus

Amylin, a peptide, which was isolated from the islet amyloid of type II diabetics, might play a potential role in the pathogenesis of type II diabetes mellitus. In in vitro and in vivo studies it has been shown that amylin has an effect on insulin secretion as well as on insulin sensitivity. From measurements of plasma amylin levels it is known that amylin is cosecreted with insulin and patients with hyperinsulinemia have also elevated amylin levels. In patients with impaired glucose tolerance and type II diabetes amylin levels are decreased compared to insulin. A secretory defect of amylin and its local accumulation in the islets of type II diabetics might be a cause for the insulin secretory defect in type II diabetes. Additionally, amylin can induce peripheral insulin resistance, which might also be a cause for type II diabetes mellitus. Amylin is a new pancreatic peptide, which might play an important role in the pathogenesis of diabetes mellitus.     

A型行为对原发性高血压患者血浆儿茶酚胺的影响

本研究对１００例原发性高血压病人和１００例正常人进行Ａ型行为问卷的测试，并对原发性高血压组中测示为Ａ型行为，Ｂ型行为的各２０例患者及正常人群组２０例Ａ型行为者进行血浆儿茶酚胺的测定，结果显示：（１）正常人群组Ａ、Ｂ型行为的血浆儿茶酚胺（ＣＡ）水平在正常范围，两型间无差异；（２）原发性高血压组Ａ型行为者ＣＡ水平明显高于Ｂ型行为的ＣＡ水平；（３）高血压组Ａ型行为ＣＡ水平明显高于正常组的Ａ型行为的ＣＡ水平。由此提示：Ａ型行为可能对影响原发性高血压病的预后具有危险性。     

Reduction of mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by combined treatment with clofibrate and nicotinic acid

Consecutive survivors of a myocardial infarction from the Southern Hospital, below 70 years of age, were randomized into a Control group (n = 276) and a Treatment group (n = 279). The latter was openly prescribed the combination of clofibrate and nicotinic acid for serum lipid lowering. Each patient should remain in the study for 5 years and be seen regularly every 4 months at a special IHD outpatient clinic within the hospital. The concentration of serum cholesterol and triglyceride was lowered by 13% and 19%, respectively, in the Treatment group compared to the Control group. Total mortality was 82 cases in the Control group and 61 in the Treatment group, a 26% reduction (p less than 0.05). For patients above 60 years of age in the Treatment group the reduction in mortality was 28% (p less than 0.05). IHD mortality was reduced by 36% (p less than 0.01) in the Treatment group compared to the Control group. The beneficial effect of the serum lipid lowering treatment was related to the serum triglyceride concentration in two ways. First, it only occurred in patients with a triglyceride level greater than 1.5 mmol/l (n = 216). Secondly, it was most pronounced in the 44% of the treated patients who had a lowering of the serum triglyceride by 30% or more, and in this subgroup the reduction of IHD mortality was 60% (p less than 0.01). For serum cholesterol there were no such relations. The difference between serum triglycerides and cholesterol concerning these relations to the treatment outcome may be due to the fact that hypertriglyceridaemia was the most common hyperlipidaemia among our patients, occurring in 50%, while hypercholesterolaemia only occurred in 13%. Caution should be exercised in the interpretation of the results as the trial was not blind. However, the fact that the decrease in IHD deaths was directly related to the degree of serum triglyceride lowering indicates that it was the drug effect on serum lipids that was responsible for the beneficial effect of the treatment.     

Hyperhomocysteinaemia and type 2 diabetes

OBJECTIVES: Hyperhomocysteinaemia is associated with cardiovascular events in nondiabetic individuals. The present study was aimed to explore the implication of hyperhomocysteinemia in development of cardiovascular events in patients with type 2 diabetes. DESIGN: A total of 185 patients with type 2 diabetes (115 women and 70 men, 30 to 93 years of age) have been included consecutively in the ambulatory unit at the Saint-Philibert Hospital. For each patient the concentration of homocysteine, cholesterol and triglyceride levels and HbA1c have been measured. In the studied population, 121 patients presented cardiovascular events (myocardial infarctus, peripheric arteriopathy, cerebrovascular accident). RESULTS: The patients with cardiovascular events were older, the concentration of homocysteine and creatinine were higher. The plasma homocysteine levels adjusted for age and creatinine levels were higher in patients with cardiovascular events than in patients without cardiovascular events (15.4 +/- 3.52 micromol/L and 13.13 +/- 2.26 micromol/L respectively; p = 2. 10(-5)). CONCLUSIONS: Hyperhomocysteinemia is an independant risk factor for cardiovascular events in type 2 diabetes, independent of age and renal function.     

Bezafibrate induces FALDH in human fibroblasts; implications for Sjögren-Larsson syndrome

Sj?gren-Larsson syndrome (SLS) is caused by a deficiency of fatty aldehyde dehydrogenase (FALDH), encoded by the ALDH3A2 gene. In animal studies, the expression of the murine ortholog of FALDH, has been shown to be under the control of peroxisome proliferator-activated receptor alpha (PPARalpha). In the present study, we investigated whether the hypolipidemic drug bezafibrate, which is a pan-agonist of all PPAR-isoforms, might induce FALDH activity in human fibroblasts of control subjects and SLS patients that still have some residual FALDH activity. Our results show that FALDH activity was induced 1.4-fold after a 3-day treatment with 800 microM bezafibrate in fibroblasts of control subjects. Interestingly, in fibroblasts of two SLS patients homozygous for the p.R228C substitution, FALDH activity could be induced to 37% of control values by bezafibrate treatment. mRNA analysis in fibroblasts of these patients also revealed a mean 1.8-fold induction of FALDH mRNA after bezafibrate treatment. No induction was observed in fibroblasts of patients with mutations that cause instability of FALDH mRNA or that result in a protein without any residual activity. These data suggest that bezafibrate treatment could be effective in patients with expression of FALDH protein and some residual enzyme activity. Further research is needed to resolve whether patients could benefit from treatment with bezafibrate.     

Disorders of fatty acid composition and the processes of lipid peroxidation in chronic ischemic heart disease

The levels of lipid fractions, free and bound fatty acids, initial and end lipid peroxidation products in the blood plasma, red cell membrane resistance to hemolysis, and myocardial contractility before, during, and after therapy with lipostabil forte (0.6-1.8 g daily or 10 ml (0.5 g) i.v.) and bezafibrate (0.2 g 3 times daily) along with nitrates (10 to 30 tablets) have been examined by the routine methods in 159 patients with stable angina pectoris and postinfarction cardiosclerosis. A negative effect of high doses of nitrates on myocardial hemodynamics and fatty acid composition has been revealed, resulting in accumulation of bound fatty acids. Lipostabil has improved the patients' status, myocardial function, and lipid composition, reduced the levels of atherogenic lipids and lipid peroxidation products, as well as the concentration of fatty acids with an uneven number of C atoms, increased the fatty acid nonsaturation index and the level of medium-strand fatty acids. Improvement of the patient's condition in bezafibrate therapy has been less evident; the concentration of atherogenic lipids has been reduced, but the levels of bound fatty acids and of lipid peroxidation products has increased. Bezafibrate is recommended to be administered together with antioxidants.     

苯扎贝特改善2型糖尿病合并高甘油三酯血症患者 胰岛素抵抗的临床分析

目的 探讨苯扎贝特对2型糖尿病合并高甘油三酯血症患者降低血脂,同时改善胰岛素敏感性的影响及作用机制。方法选取我院2016年12月~2018年2月收治的符合入选标准2型糖尿病合并高甘油三酯血症患者56例,随机分为A组（n=29）和B组（n=27）。两组均使用苯扎贝特及非诺贝特降脂治疗,其他常规服用药物不变。A组:治疗顺序为苯扎贝特+非诺贝特,疗程各1个月,期间清洗期为1周;B组:治疗顺序为非诺贝特+苯扎贝特,疗程各1个月,期间清洗期为1周。监测两组患者实验前、第一阶段及第二阶段的甘油三酯（TG）、胆固醇、空腹血糖（FBG）、糖化血红蛋白（HbA1c）、空腹胰岛素（FINS）,并计算胰岛素敏感指数（IsI）。结果 两组患者实验前、第一阶段和第二阶段的TG和胆固醇水平比较,差异无统计学意义（P＞0.05）。两组实验前和第一阶段的FBG、HbA1c及IsI比较,差异无统计学意义（P＞0.05）;B组第二阶段的FBG高于A组[（6.73±0.28）mmol/L vs （6.52±0.51）mmol/L],HbA1c和IsI均低于A组[（6.54±0.32）% vs （6.76±0.71）%,（-4.19±0.34）vs（-4.13±0.28）],差异有统计学意义（P＜0.05）。结论 苯扎贝特可改善血脂,调节糖代谢,降低2型糖尿病患者血糖,并能改善胰岛β细胞分泌功能,提高机体胰岛素敏感性。     

Human granulosa cells express integrin alpha2 and collagen type IV: possible involvement of collagen type IV in granulosa cell luteinization.

Previously, it has been shown that integrin alpha6beta1 expressed on human granulosa cells regulates luteinization in co-operation with its ligand, laminin. In this study, integrin alpha2 was immunohistochemically demonstrated to be expressed on granulosa and large luteal cells. It was also detected on luteinizing theca interna cells after ovulation. Immunoreactive collagen type IV, which is one of the ligands for integrin alpha2beta1, was detected around granulosa cells in the pre-ovulatory follicles and its expression was rapidly increased during ovulation. By flow cytometry, collagen type IV was detected on the cell surface of luteinizing granulosa cells isolated from pre-ovulatory follicles, confirming the physiological interaction between granulosa cells and collagen type IV. Collagen type IV in follicular fluid was positively related with progesterone concentration. In 4-day cultures of granulosa cells, collagen type IV in the media was significantly increased by human chorionic gonadotrophin (HCG). The progesterone production was significantly attenuated when granulosa cells were cultured on collagen type IV-coated dishes, suggesting that collagen type IV suppresses granulosa cell luteinization. These findings show that collagen type IV, a ligand for integrin alpha2beta1, is rapidly produced around luteinizing granulosa cells during ovulation, probably under the control of luteinizing hormone (LH) and suggest that collagen type IV is a new parameter and/or regulator of granulosa cell luteinization in the periovulatory phases.     

Staining pattern of type IV collagen and prognosis in early stage adenocarcinoma of the lung.

AIMS--To examine the prognostic value of basement membrane expression in early stage adenocarcinoma of the lung. METHODS--Using antibodies to type IV collagen, basement membrane expression at the tumour-stromal border was immunohistochemically analysed in 30 patients with early stage adenocarcinoma of the lung (pstage I and pstage II). Two patterns of staining for type IV collagen were observed: in the first one the staining line was conserved or partially fragmented; in the second the staining line was widely fragmented or absent in more than 10% of the tumour area. The first staining pattern was categorised as continuous and the second as discontinuous. RESULTS--Of the 24 patients with pstage I adenocarcinoma, 12 (50%) cases showed a continuous pattern. In only one (16.7%) of the six patients with pstage II adenocarcinoma was this pattern evident. Five year survival was greater in pstage I adenocarcinoma (65%) than in pstage II adenocarcinoma (17%), but the difference was not significant. When the analysis was restricted to the 24 patients with pstage I adenocarcinoma, five year survival was better in continuous pattern cases (88%) than in discontinuous pattern cases (20.5%) (p < 0.05). The survival curve of 12 patients with pstage I adenocarcinoma and a discontinuous pattern resembled that of the six patients with pstage II adenocarcinoma. CONCLUSION--These findings suggest that patients with pstage I adenocarcinoma and a discontinuous pattern have histopathologically unrecognised micrometastasis when they come to surgery. The staining pattern of type IV collagen could help in the prognosis of pstage I adenocarcinoma of the lung after surgery.     

Long-term effect of clofibrate on albumin turnover and distribution in man

The long-term effect of clofibrate (at least 6 months' treatment) on albumin metabolism was investigated in 7 subjects and the results were compared with those from 15 control subjects. Human albumin labelled with 131I was used as a tracer. A significant difference between the groups was found in the following parameters: The clofibrate-treated group had a prolonged rapid component (t1 1/2) of the disappearance curve (p less than 0.05), relatively increased albumin in the extravascular space (i.e. decreased distribution ratio, p less than 0.01) and increased extravascular albumin space when corrected for body size by calculating it as per cent of the extravascular bromide space (p less than 0.01). There was no significant difference between the groups in albumin synthesis, fractional catabolic rate or the slow component (t2 1/2) of the disappearance curve. The results suggest that long-term treatment with clofibrate causes changes in the intercellular matrix.     

Fibrates and their newly synthesized glycinate or glycinate-methylester derivatives: comparison of the interactions with liver cytochrome P450 dependent monooxygenase- and oxidase-functions in vitro.

Different fibrates (bezafibrate, ciprofibrate, clofibrate, fenofibrate, gemfibrozil) were investigated in comparison with their newly synthesized glycinate and glycinate-methylester derivatives. Interactions with the cytochrome P450 (CYP) system were studied by assessing binding to CYP and effects on CYP mediated monooxygenase functions in rat liver 9000 g supernatants, as measured by six model reactions for different CYP isoforms (ethoxyresorufin O-deethylation, ethoxycoumarin O-deethylation, pentoxyresorufin O-depentylation, p-nitrophenol-hydroxylation, ethylmorphine N-demethylation, lauric acid 11- or 12-hydroxylation). Possible prooxidant or antioxidant properties were investigated by the stimulated lipid peroxidation, hydrogen peroxide production, and lucigenin and luminol amplified chemiluminescence using rat liver microsomes. Additionally, the influence on luminol amplified rat whole blood chemiluminescence was examined.

All substances tested displayed binding to CYP. Effects on the monooxygenase model reactions were in general more distinct with the glycinates than with the parent compounds and most pronounced with the glycinate-methylester derivatives. The slightest effects on all model reactions were seen with clofibrate and its derivatives.

On the whole, low antioxidative rather than prooxidative effects were observed. In general and with most model reactions, the antioxidative capacity of the glycinate and glycinate-methylester derivatives slightly exceeded that of the respective parent compounds.

Summarizing the results it can be concluded that with respect to possible interactions with the CYP system in vivo and thus with the biotransformation of other concomitantly administered compounds no advantages of the glycinate or glycinate methylester derivatives over their parent fibrates are to be expected. Only the antioxidative capacity of the derivatives was somewhat higher than that of the parent substances, though most probably only of minor therapeutical relevance.