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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The plasma lipoprotein and liver lipid composition, and the lipid, cholesterol and apolipoprotein synthesis have been studied in normal and diet-induced hyperlipidemic rats, receiving ciprofibrate (2.5 mg/kg body weight) or fenofibrate (50 mg/kg b.w.) for 8 days. Ciprofibrate is about 25-fold more active than fenofibrate in reducing plasma triglyceride and cholesterol concentrations both in normolipemic and in hyperlipemic rats. In normolipemic rats ciprofibrate reduced the concentration and the lipid content of all lipoprotein classes. The incorporation of [14C]palmitate and [3H]leucine into the lipoproteins was reduced by ciprofibrate and fenofibrate. The reduction in lipoprotein production was confirmed by prevention of Triton-induced hyperlipemia. Liver and plasma cholesterol synthesis estimated by 3H2O and [14C]mevalonate incorporation indicated an inhibitory effect on HMG-CoA reductase. Administration of ciprofibrate or fenofibrate to rats fed a fat and cholesterol-rich diet partially prevented liver steatosis and hyperlipemia. Both drugs reduced the overproduction of lower density lipoproteins. The ratio of (VLDL + LDL)-cholesterol/HDL-cholesterol which was increased by the diet alone from 0.4 (normal) to 11 remained close to the normal value in the animals receiving ciprofibrate. In the hyperlipemic animals, ciprofibrate reduced the incorporation of [3H]oleate into the liver and plasma glycerolipid and increased cholesterol esterification. Ciprofibrate efficiently reduces plasma levels of cholesterol, triglyceride and phospholipid. Cholesterol and glycerolipid synthesis in the liver were significantly reduced leading to a lower lipoprotein secretion rate in both normolipidemic and diet-induced hyperlipidemic rats.
Atherosclerosis 1988 Dec
PMID:Effects of ciprofibrate and fenofibrate on liver lipids and lipoprotein synthesis in normo- and hyperlipidemic rats. 324 Mar 33

In a double-blind study over a 3-month period, a daily dose of 100 mg ciprofibrate, prescribed in a single administration and a daily dose of 300 mg fenofibrate, prescribed in 3 administrations, significantly reduced the mean values of total cholesterol, LDL cholesterol and VLDL cholesterol, apoprotein B (P less than 0.001) and increased the mean values of HDL cholesterol (P less than 0.01) and total apoprotein A (P less than 0.05). The study, followed-up as an open trial using higher doses (100 or 200 mg/day ciprofibrate, 400 mg/day fenofibrate) tried to demonstrate clearly the benefit of therapy after 9 months with the 2 drugs and to establish the dose-response effects. Comparison of the 2 drugs at the optimal dosages, after 9 months of treatment, showed ciprofibrate to be more effective in increasing HDL cholesterol (P less than 0.05) and apo A (P less than 0.001). No other significant differences in terms of either therapeutic efficacy or biological tolerance became apparent between the 2 drugs. The results obtained in this comparative study were in accordance to those observed in separate trials for ciprofibrate or fenofibrate. Ciprofibrate has the benefit of a long half-life and may also be administered in the form of a single daily dose to patients suffering from major type II hyperlipoproteinaemia.
Atherosclerosis 1985 Mar
PMID:Comparative evaluation of the effects of ciprofibrate and fenofibrate on lipids, lipoproteins and apoproteins A and B. 399 83

The effect of ciprofibrate, 2[p-(2,2-dichlorocyclopropyl)-phenoxyl]-2-methyl propionic acid, in daily doses of 50, 100, and 200 mg was studied in 50 patients with hyperlipoproteinaemia (21 type IIA, 10 type IIB and 19 type IV). Ciprofibrate was convenient to take and was without subjective side effects. The greatest hypolipidaemic effects were reached for all lipoproteins with 200 mg daily. In type IIA and IIB, mean low density lipoprotein (LDL) cholesterol was normalized on the 200 mg dose. The effect was highly dependent on initial LDL cholesterol concentrations, decreases being observed above 4 mmol/l and increases below that concentration. Mean very low density lipoprotein (VLDL) triglyceride concentrations decreased on 200 mg per day by 48-59%. HDL cholesterol increased in all types of hyperlipoproteinaemia by 6-19%, the change being unrelated to changes in VLDL lipids. With a dosage of 200 mg daily the effects were maintained for the following period of 6 months. It is concluded from this study that it would be appropriate to start patients on 100 mg daily and then titrate their dose according to response. The optimal dosage for ciprofibrate seems to be 200 mg daily.
Atherosclerosis 1982 Apr
PMID:Dose-response study of the effect of ciprofibrate on serum lipoprotein concentrations in hyperlipoproteinaemia. 695 82

This study examined the effects of ciprofibrate therapy (100 mg/day) on plasma lipids, lipoproteins and low density lipoprotein (LDL) kinetic heterogeneity in moderately hypercholesterolaemic subjects. The drug lowered plasma triglyceride and cholesterol by 41% and 17%, respectively. Very low density lipoprotein (VLDL) cholesterol fell by 38%, LDL cholesterol fell by 22%, while the content of the lipid in high density lipoprotein (HDL) increased by 11%. LDL structural and metabolic heterogeneity were assessed before and during therapy in eight subjects. Density gradient centrifugation was used to fractionate LDL into three species. LDL-I, the least dense, was not affected by therapy whereas LDL-II and LDL-III were decreased by 28% (P < 0.01) and 31% (N.S.). Baseline turnover studies revealed that LDL catabolism was subnormal and this was the cause of the raised cholesterol in these subjects. Ciprofibrate therapy increased the apoLDL fractional catabolic rate (FCR) by 19%, principally by inducing a 38% enhancement (P < 0.03) in apoLDL removal by the receptor pathway. ApoLDL kinetics exhibited metabolic heterogeneity both before and during drug therapy. Analysis of plasma decay curves for the LDL tracer and urinary excretion data indicated that the lipoprotein comprised two metabolically distinct species, one with an FCR of about 0.50 pools/day (Pool A), the other with an FCR of about 0.18 pools/day (Pool B). Drug therapy decreased synthesis of and hence reduced the plasma mass of apoLDL in the slow metabolised pool B. This perturbation in synthesis was linked to the change in plasma triglyceride concentration. The resultant reduced proportion of pool B vs. pool A material accounted for the observed promotion of LDL receptor-mediated clearance. Ciprofibrate, therefore, produced beneficial changes in the plasma levels of VLDL, LDL and HDL and in the metabolism of LDL.
Atherosclerosis 1994 Aug
PMID:Effects of ciprofibrate on LDL metabolism in man. 798 Jul 13

The effect of ciprofibrate treatment on the atherogenic profile of low-density lipoprotein (LDL) subspecies in combined hyperlipidemia (CHL) has been investigated in six patients displaying elevated plasma triglyceride and cholesterol levels (> 200 and > 250 mg/dl, respectively). The E2E2 phenotype was excluded; four patients possessed familial antecedents of premature coronary heart disease (CHD). Analysis of five LDL subclasses separated by isopycnic density gradient ultracentrifugation showed a predominance of dense LDL subspecies (LDL-4 and LDL-5, d 1.039-1.063 g/ml; 51% of total LDL mass) in the asymmetric LDL density profile characteristic of CHL patients at baseline. Ciprofibrate treatment (100 mg/day for 1 month) effected marked reductions in both total plasma LDL and apo B-100 levels (approximately 19% and approximately 23%, respectively). Equally, the plasma profile of LDL subspecies was normalised to a significant degree as a result of preferential reduction in the elevated levels of both dense subspecies (LDL-4 and LDL-5; -43% and -54%, respectively; P < 0.03 and P < 0.006 [corrected], respectively). The circulating concentrations of light LDL (LDL-1, d 1.019-1.023 g/ml) were also diminished significantly by ciprofibrate (-30%; P < 0.006 [corrected]). Furthermore, ciprofibrate not only effected reductions in the elevated triglyceride content of the hydrophobic core of all LDL subspecies but also normalised their common deficiency in free cholesterol. In addition, the abnormally small particle diameters of LDL-4 and -5 were increased to normal. Plasma levels of both apo B-100 and triglycerides were significantly and positively correlated with those of LDL-4 and LDL-5, suggesting not only that the degree of triglyceride elevation is intimately linked to the extent of shift in LDL subclass profile towards denser subspecies, but also that triglyceride reduction upon treatment strongly influences LDL-4 and LDL-5. In conclusion, our findings indicate that ciprofibrate treatment in combined hyperlipidemia results in marked reduction in plasma triglyceride levels (-33%), and that such reduction is intimately linked to normalisation of both the qualitative and quantitative features of the atherogenic LDL subspecies profile typical of this disorder.
Atherosclerosis 1993 Apr
PMID:Ciprofibrate therapy normalises the atherogenic low-density lipoprotein subspecies profile in combined hyperlipidemia. 831 67

The efficacy and short-term safety of ciprofibrate and gemfibrozil were compared in a 12-week, double-blind, randomised study. One-hundred-and-ten primary, type II hyperlipidaemic patients were randomised to receive either ciprofibrate, 100 mg/day once daily, or gemfibrozil, 1200 mg/day twice daily. Treatment efficacy was measured by complete lipid and lipoprotein profiles and by plasma fibrinogen levels. Tolerability was assessed by drug compliance and safety was evaluated by laboratory safety parameters, physical examination and evaluation of adverse events. Mean reductions of plasma TC and low density lipoprotein cholesterol levels were similar in the two treatment groups. In contrast, the mean relative reduction of plasma total triglyceride and very low density lipoprotein triglyceride levels was significantly higher in patients receiving gemfibrozil as compared with ciprofibrate (P < 0.05). The absolute reduction of the last two parameters was higher in the ciprofibrate group compared with the gemfibrozil group; furthermore, the mean concentrations of these parameters were within normal limits at the end of the study. The clinical relevance of the statistically significant difference mentioned should, therefore, be questioned. Ciprofibrate therapy significantly reduced (-8.33%) and gemfibrozil therapy significantly increased (+6.97%) plasma fibrinogen levels (P < 0.001 compared with baseline in each case). Adverse events were rare, mild and equally distributed between the two treatment groups. Laboratory safety parameters did not show any significant changes. Ciprofibrate and gemfibrozil have comparable short-term efficacy and safety profiles. Furthermore, ciprofibrate reduces fibrinogen levels and benefits from a once daily regimen.
Atherosclerosis 1996 Jul
PMID:Ciprofibrate versus gemfibrozil in the treatment of primary hyperlipidaemia. 883 19

Ciprofibrate is an effective treatment for three main types of atherogenic hyperlipoproteinaemia: type IIa hypercholesterolaemia, type IIb combined hyperlipidaemia, and type IV hypertriglyceridaemia. In type IIa hypercholesterolaemia, administration of 100 mg/day of ciprofibrate, to approximately 3000 patients, decreased total cholesterol (TC), triglycerides, apolipoprotein B (apo B) and low-density lipoprotein (LDL) cholesterol. Levels of apolipoproteins in high-density lipoprotein (HDL) cholesterol and apolipoprotein AI (apo A-I) were increased. Administration of the same dose of ciprofibrate, to approximately 3500 patients with type IIb combined hyperlipidaemia, had a marked cholesterol- and triglyceride-lowering effect, in addition to producing a decrease in LDL cholesterol and apo B, and an increase in apo A-I. TC levels were also decreased in type IV hypertriglyceridaemia following administration of 100 mg/day of ciprofibrate to 800 patients. The decrease in TC levels was attributable to a decrease in triglyceride levels and an increase in HDL cholesterol levels. The pharmacokinetics, mechanism of action and safety of ciprofibrate treatment are also discussed.
Atherosclerosis 1996 Jul
PMID:Efficacy and safety of ciprofibrate in hyperlipoproteinaemias. 883 20

The oxidative modification of low density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis. LDL of subjects with atherogenic lipoprotein phenotype (ALP) is known to be more susceptible to oxidation. We studied the effect of the hypolipidaemic drug ciprofibrate on the susceptibility of LDL to in vitro oxidation. Nine patients with primary hypertriglyceridaemia and hypoalphalipoproteinaemia (mean plasma triglycerides 3.76 mmol.l-1 and HDL-cholesterol 0.74 mmol.l-1) were treated with ciprofibrate for 12 weeks. The susceptibility of LDL to in vitro Cu(2+)-mediated oxidation was assessed by measuring conjugated diene formation at 234 nm. Ciprofibrate therapy significantly prolonged the lag time (93 +/- 7 min vs. 102 +/- 11 min, P = 0.02). The maximal rate of diene production was 11% lower, but the decrease was not significant. A significant positive correlation was observed between maximal rate and maximal amount of dienes formed. Thiobarbituric acid reacting substances (TBARS) and lipid hydroperoxides (LPO) in oxidatively-modified LDL, isolated from the plasma of patients before and after drug treatment, were unchanged. The results suggest that ciprofibrate therapy has a favourable effect by increasing the in vitro resistance of LDL against oxidation.
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PMID:Oxidation resistance of LDL in hypertriglyceridaemic patients treated with ciprofibrate. 980 83

Ciprofibrate is one of the basic drugs used to lower risk values of lipid parameters and fibrinogen in atherosclerosis patients. Since antiaggregation treatment with acetylsalicylic acid is a complex part of obligatory therapy of these patients, the authors studied the influence of ciprofibrate on chosen lipid parameters, fibrinogen and thromboxane in monotherapy, and also in combination with acetylsalicylic acid (ASA) in patients with advanced atherosclerosis and hyperlipoproteinemia. In the first group of patients (A-C, n = 12) after one month of low-lipid diet acetylsalicylic acid in a dose of 100 mg was administered daily during a period of 2 months followed by addition of 100 mg of ciprofabrate daily during the next 2 months. In the second group of patients (C-A, n = 11) after one month of low-lipid diet the same drugs were administered but in opposite order. Ciprofibrate was most effective in lowering the levels of triacylglycerids (-41%) and VLDL-cholesterol (-34%), but effectively lowered also the values of total cholesterol and LDL-cholesterol. In both studied groups it led to mild increase of HDL-cholesterol levels. Simultaneous administration of ASA did not significantly influence its hypolipemic activity. Ciprofibrate also significantly lowered the level of fibrinogen (-17%). Increase of the total number of platelets by about 10% was not accompanied by changes of the values and production of thromboxane. Simultaneous administration of ASA caused more than 90% inhibition of thromboxane production in monotherapy and in combination with ciprofibrate. Ciprofibrate is an effective hypolipidemic agent, also lowering the level of fibrinogen. Its combination with ASA is adequate, safe and without negative interaction influencing treatment. (Tab. 6, Fig. 1, Ref. 16.)
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PMID:[The effect of monotherapy with ciprofibrate and in combination with acetylsalicylic acid on the spectrum of lipids, thromboxane and fibrinogen in patients with atherosclerosis and hyperlipoproteinemia]. 1064 34

Fibrates, besides their hypolipidemic action, share alternative effects, such as decreased plasma fibrinogen and uric acid levels. Because of their complex action, additional effects have been investigated. A group of 23 patients with clinical signs of atherosclerosis and hyperlipoproteinemia was randomly allocated after a 1-month washout period and treated with either 100 mg/d of ciprofibrate or 100 mg/d of aspirin for 2 months. Patients were then treated with a combination of these two agents for the next 2 months. Ciprofibrate decreased plasma concentrations of triglycerides (-29%) and very-low-density lipoprotein cholesterol (-27%) in monotherapy and a larger reduction was observed if ciprofibrate was added to the aspirin therapy: triglycerides (-39%), very-low-density lipoprotein cholesterol (-33%), total cholesterol (-18%), low-density lipoprotein cholesterol (-17%), and increased high-density lipoprotein cholesterol (+36%). Ciprofibrate increased plasma levels of platelet-derived growth factor (PDGF) AB in both monotherapy patients (+162.9 pg/ml, +297%) and in aspirin-pretreated patients (+129.8 pg/ml, +134%); the increase of PDGF AB platelet store was significant only in aspirin-pretreated patients (+11.1 ng/ml, +51%). Aspirin in monotherapy did not modulate either plasma or platelet store of PDGF AB. Ciprofibrate did not inhibit thromboxane B 2 synthesis in platelets. Aspirin did not influence plasma thromboxane B 2 concentration at all, whereas it decreased thromboxane B 2 platelet production markedly in monotherapy (-85%) and in combination with ciprofibrate (-91%). Ciprofibrate increases PDGF AB content, which is amplified by aspirin pretreatment without correlation with its hypolipidemic action. The increase of PDGF production is suggested to participate in plaque stabilization.
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PMID:Ciprofibrate increases plasma concentration of platelet-derived growth factor AB in patients with advanced atherosclerosis and hyperlipidemia independently of its hypolipidemic effects. 1160 11


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