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At least 19 recordsLinked to original sources
PubMed1980

[Evaluation of the antilipaemic potential of etofylline clofibrate, its metabolites and clofibrate in dietary-induced hyperlipidaemia in the rat (author's transl)].

Efficacy of 1-(theophyllin-7-yl)-ethyl-2-[2-(p-chlorophenoxy)-2-methylpropionate] (etofylline clofibrate, ML 1024, Duolip) and its molecule components (metabolites) of structurally similar theophylline esters and of clofibrate as standard was investigated in the artificial hyperlipidaemia of the rat. In accordance with former results etofylline clofibrate was antilipaemically active and, in contrast to similar esters and clofibrate, significantly decreased the cholesterol level. An investigation of the efficacy of its metabolites, either alone or in equivalent mixture, as well as of the standard clofibrate under fat diet demonstrated low efficacy of etofylline, but an increased activity in combination with clofibrate or clofibric acid. The activity of the combination is significantly superior to that of clofibrate under fat diet, but not under normal diet. The increased efficacy of etofylline clofibrate is undoubtedly an unusual potentiation, an additive effect of the metabolites can be excluded. Cholesterol and triglycerides are relevant parameters for the experimental evaluation of the efficacy. Measurement of total lipids offers no additional information. Substitution of triglycerides by total-beta-lipoproteins as parameter seems methodically useful, since values of cholesterol, triglycerides and beta-lipoproteins correlate well under normal diet.

Animals↗
PubMed1977

Clofibrate and clofibric acid: comparison of the metabolic disposition in rats and dogs.

In rats, equimolar oral doses of [14C]clofibrate and [14c]clofibric acid produced essentially the same profiles of blood levels, tissue distribution and excretion of radioactivity. Both compounds were completely absorbed, and all radioactivity found in the serum was due to clofibric acid (CPIB). Tissues contained readily detectable radioactivity levels, but the concentration was generally lower than in serum. A large proportion of CPIB in liver, heart, kidney, fat and muscle was associated with intracellular space. In rat urine, CPIB was present both free and conjugated with glucuronic acid. Approximately 97% of the serum CPIB was not conjugated. Identical decreases in serum lipids and hepatic cholesterol synthesis were observed in rats treated for 1 week with either compound. In dogs, the serum contained 40% more radioactivity after [14C]clofibric acid than after an equimolar oral dose of [14C]clofibrate; approximately 88% of the serum radioactivity was due to CPIB. Some biliary excretion was detected. The extent of binding to serum protein varied with concentration of CPIB and with the species; the affinity was in the order man greater than dog greater than rat. The results demonstrate that clofibric acid and clofibrate are metabolically and pharmacologically equivalent in rats, but not in dogs. The data are in accordance with the view that the pharmacological activity of clofibrate is due to clofibric acid.

Animals↗
PubMedDate not supplied

Species differences in the metabolic conjugation of clofibric acid and clofibrate in laboratory animals and man.

The urinary metabolites of single doses of clofibric acid (p-chlorophenoxyisobutyric acid), and its ethyl ester, clofibrate, have been investigated in rat, guinea pig, rabbit, dog, cat, ferret, and human volunteers. Human volunteers, rodents, and rabbits given clofibric acid excreted 60-90% of the 14C dose in the urine in 24 hr, and the only metabolite found was the ester glucuronide of clofibric acid, together with small amounts of the unchanged acid. In the dog, cat, and ferret, however, urinary excretion of 14C was much slower (23-39% of dose in 24 hr) and these species all formed the taurine conjugate of clofibric acid, excreted together with the unchanged acid. The ester glucuronide was found in the urine of dog and ferret but not cat. The fate of clofibrate, the ethyl ester of clofibric acid, in rat, guinea pig, rabbit, and man was similar to that of the parent acid. The characterization of the glucuronic acid and taurine conjugates of clofibric acid is described.

Animals↗
PubMed1980

[Clofibrate therapy in hypercholesterolemia. Reports on medium-long-term movements of HDL- cholesterol by the action of clofibrate].

Clofibrate was administered to 5 selected outpatients suffering from type IIa hyperlipoproteinaemia who had previously undergone dietetic treatment, and one female patient suffering from hypo-HDL-aemia in order to elucidate the question as to whether medium long term clofibrate therapy apart from producing an initial increase relative to the LDL concentration may also lead to an absolute increase in the concentration of HDL cholesterol in serum. According to our findings daily doses of 1 to 2 g clofibrate increase the concentrations of HDL cholesterol and phospholipids within two to four months after therapy was started. These increases remained unchanged within four to eight weeks after having reduced the dose to half its original level. Subsequent HDL cholesterol levels still range above those of the controls prior to clofibrate treatment. After a further clofibrate dose at the original dose level it takes again four to eight weeks until the HDL cholesterol level increases again. Thus, during medium long term therapy the quantitative effect of clofibrate on the lipoprotein pattern is similar to that of bezafibrate and etofibrate. It is only the latency period of an increase in serum concentration of HDL cholesterol that differs: it is longest for clofibrate, shortest for etofibrate, with bezafibrate obviously being right in the middle.

Adult↗
PubMed1980

Changes in the fatty acid composition of the plasma lipid esters during lipid-lowering treatment with diet, clofibrate and niceritrol. Reduction of the proportion of linoleate by clofibrate but not by niceritrol.

The fatty acid composition of the plasma lipid esters has been studied during lipid-lowering treatment of 95 patients with atherosclerotic disease. During the first two months of the trial only a diet was prescribed. During the ensuing two months either clofibrate or niceritrol, a nicotinic acid ester, was added in a randomized order. During the last two months the second drug was added. The combined treatment with diet, clofibrate and niceritrol caused highly significant serum lipid reductions. The fatty acid composition in the plasma lipid esters was determined in samples from each trial period to measure the degree of dietary adherence. During dietary treatment the relative content of saturated and monounsaturated fatty acids secreased and the polyunsaturated fatty acids increased with an increasing ratio between pulyunsaturated and saturated fatty acids (P/S ratio) in the cholesterol esters and triglycerides. Only minor changes were seen in the phospholipids. The changes caused by the diet were partly reversed by clofibrate while niceritrol did not cause any major changes of the fatty acid composition. Clofibrate treatment coincided with increasing amounts of monounsaturated fatty acids, especially oleate (18 : 1), in the cholesterol esters, triglycerides and phospholipids while there were significant reductions of the content of linoleic (18 : 2) acid in both the cholesterol esters and triglycerides. The 18 : 2/18 : 1 ratio decreased significantly in all the lipid esters analyzed. However, the P/S ratio was not significantly affected, partly because the relative content of saturated fatty acids also tended to decrease during clofibrate treatment. It is concluded that addition of clofibrate treatment to patients who are on a diet enriched with polyunsaturated fats is associated with a change from polyunsaturated to monounsaturated fatty acids in the plasma lipid esters but does not significantly effect the ratio between polyunsaturated and saturated fatty acids. The fatty acid changes caused by clofibrate treatment and counteracted by an increased amount of polyunsaturated fat in the diet.

Aged↗
PubMed1986

Separation and measurement of clofibroyl coenzyme A and clofibric acid in rat liver after clofibrate adminstration by reversed-phase high-performance liquid chromatography with photodiode array detection.

A method to identify and quantitate clofibric acid and clofibroyl coenzyme A (CoA) products in rat liver was developed using reversed-phase high-performance liquid chromatography. The system was developed with baseline separation of clofibroyl-CoA from clofibric acid using isocratic elution, with a mobile phase consisting of 52% methanol and 28 mM potassium phosphate buffer (pH 4.2). With this high methanol concentration, the large amount of UV-absorbing materials present in the liver extracts were eluted earlier than the investigated compounds. Clofibroyl-CoA has a characteristic absorbance spectrum with distinct peaks at 260 and 230 nm, while clofibric acid showed only a distinct peak at 230 nm. Using an on-line photodiode array detector, the spectra could be recorded during analysis without interrupting the flow of the mobile phase. This spectral analysis identification possibilities and evaluation of the purity of the chromatographic peaks. In a perchloric extract of rat liver, the recovery of clofibric acid and clofibroyl-CoA added to the liver extract ranged from 70 to 80%. A linear relationship was observed between clofibric acid and clofibroyl-CoA concentration and the area of their peaks in the chromatogram. The detection limit of the method was lower than 5 pmol for both compounds when the absorbance was recorded at 230 nm. The method could be used without modification for the estimation of clofibroyl-CoA and clofibric acid in biological extracts.

Acyl Coenzyme A↗
PubMed1983

The analysis of [14C]clofibric acid glucuronide and [14C]clofibric acid in plasma and urine using high-performance liquid chromatography.

A high-performance liquid chromatographic method has been developed for the quantitation of [14C]clofibric acid glucuronide and [14C]clofibric acid using conventional scintillation counting. The assay has a linear relationship between the added and observed ratios of clofibric acid glucuronide: clofibric acid in the range of 0.001-0.6 for plasma and 0.5-100 for urine, and is able to quantitate previously unmeasurable concentrations of clofibric acid glucuronide in plasma.

Animals↗
PubMed1977

Plasma clofibric acid (CPIB) levels induced by three marketed compounds releasing clofibric acid, in volunteers.

The very low plasma clofibric acid levels achieved in normolipemic volunteers during 96 h by a single dose of alufibrate (basic aluminum salt of clofibric acid) as 4 x 360 mg tablets, have been confirmed. With a crossover study in healthy volunteers receiving therapeutic doses of clofibrate as 2x500 mg capsules, clofibride as 2x450 mg capsules, twice daily for ten days, the plasma clofibric acid concentrations were already found in the therapeutic range after two days and remained above 80 mug/ml at the tenth day. On the other hand, the plasma clofibric acid concentrations measured during a ten-day administration of alufibrate as 2x360 mg tablets twice daily, were regularly found to be much lower at each time; they did not reach levels exceeding 60 mug/ml.

Adult↗
PubMed1981

The simultaneous analysis of clofibric acid and probenecid and the direct analysis of clofibric acid glucuronide by high-performance liquid chromatography.

A rapid and selective high-performance liquid chromatographic method for the simultaneous quantitative analysis of clofibric acid and probenecid in plasma and urine and for the direct analysis of clofibric acid glucuronide in plasma is described. Both methods involve direct injection of deproteinised body fluids. Concentrations of as low as 10 mg/l of clofibric acid and probenecid and 1.5 mg/l of clofibric acid glucuronide can be measured by the analysis. The coefficient of variance for these methods ranges from 1--7%.

Chromatography, High Pressure Liquid↗
PubMed1978

[Comparison between combination therapy with clofibrate and beta-pyridylcarbinol and clofibrate monotherapy (author's transl].

In order to determine whether the lipid-lowering effect of combined treatment with clofibrate and beta-Pyridylcarbinol exceeds that of clofibrate monotherapy, a double-blind crossover study was performed. 17 patients with primary hyperlipoproteinemia of Type IIa and 10 patients with primary hyperlipoproteinemia of Type IIb received either Lipofacton (1.000 mg clofibrate and 50 mg beta-pyridylcarbinol per day) or clofibrate (1.500 mg per day) for a period of 6 weeks each. Before beginning therapy and between both periods of medication, placebo was administered for 14 days. In both total plasma and in the LDL fraction the cholesterol level was lowered by less than 10% for both substances. In patients with hyperlipoproteinemia of Type IIb, the triglyceride levels were lowered by about 40%.

Adolescent↗
PubMed1980

Simultaneous GLC determination of clofibrate and clofibric acid in human plasma.

A simultaneous assay for the detection of clofibrate and its metabolite, clofibric acid [2-(p-chlorophenoxy)-2-methylpropionic acid], is described. This GLC method is rapid and does not require a derivatization step. It is sensitive to 1-microgram/ml levels of either compound in biological samples and can be used to characterize the in vivo conversion of clofibrate ester to the free acid.

Chromatography, Gas↗
PubMed1988

Modification of surfactant metabolizing cells in rat lung by clofibrate, a hypolipidemic peroxisome proliferating agent. Evidence to suggest that clofibrate influences pulmonary surfactant metabolism.

The influence of clofibrate (ethyl-alpha-p-chlorophenoxy-isobutyrate), a hypolipidemic peroxisome proliferating agent, has been tested on the lungs of adult male rats. Drug administration for 7 days caused structural changes in two types of lung cells, both of which are involved in the metabolism of the pulmonary surfactant. By light microscopy the prominent features were the presence of enlarged type II alveolar epithelial cells and foamy intraalveolar macrophages. Compared with controls, type II cells in treated rats apparently contained more numerous surfactant-containing lamellar bodies, as visualized in semi-thin sections of Epon-embedded tissue. This difference was quantified morphometrically by light microscopy: the number of lamellar bodies was estimated as the profile number per individual type II alveolar cell, transsected at its nucleus. Clofibrate administration for 7 days resulted in a significant increase in the number of the lamellar inclusions. In contrast the number of type II alveolar cells per area of lung remained unchanged. There was no evidence of atelectasis or inflammatory infiltration in the drug-treated lungs, a finding confirmed in sections of perfusion-fixed, paraffin-embedded whole lung-lobes. By electron microscopy the lamellar inclusion bodies in the type II alveolar cells in treated rats, apart from being more numerous and sometimes smaller, were morphologically identical to those in controls. The vacuolated alveolar macrophages seen in treated rats also contained various lamellar phospholipid inclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1977

Comparison of the lipid-lowering effect of clofibrate, and of clofibrate plus beta-pyridylcarbinol.

Forty-eight patients under 65 years were included in a double blind study comparing the lipid-lowering effect of clofibrate with that of beta-pyridylcarbinol combined with clofibrate. Over 4 months there was no significant difference in the lipid-lowering effect of either regime. A mean reduction of triglyceride of approximately 30% and of cholesterol of 18% was observed. Both drugs caused significantly greater reductions than placebo. No serious side-effects were noted.

Analysis of Variance↗
PubMed1979

Long-term effect of the combination of calcium clofibrate and calcium carbonate on serum total cholesterol, triglyceride and high density lipoprotein--cholesterol concentrations in hyperlipoproteinaemia. A comparative study with clofibrate.

Thirty hyperlipidaemic patients (19 with type IIA, 4 with IIB and 7 with type IV hyperlipoproteinaemia) were subjected to therapy with calcium clofibrate and calcium carbonate (4C, 2 + 2 g/day for 6 months) and the effect was compared with clofibrate (1C, 2 g/day) which was given for 6 months as well, in a single-blind placebo-controlled study. 4C and 1C decreased total serum cholesterol levels especially in subgroups IIA and IIB. 4C was somewhat more effective than 1C in decreasing (VLDL + LDL)-cholesterol in subgroup IIA. The HDL-cholesterol concentrations and the ratio of HDL-cholesterol and total cholesterol increased during treatment with both 1C and 4C. The HDL-cholesterol increase (vs. placebo) was 18%. The concentrations of serum triglycerides decreased by 33% during both treatment periods and there was no significant difference between 1C and 4C.

Adult↗
PubMedDate not supplied

Measurement of clofibric acid (CPIB) metabolites in plasma of patients on clofibrate therapy.

1. The metabolites of clofibric acid [CPIB;2-(chlorophenoxy)-2-methylpropionic acid] are present in the plasma of patients on clofibrate therapy. The highest plasma concentrations of CPIB in metabolite form (up to 51 micrograms/ml) were generally found in patients with renal disease. Negligible concentrations (less than or equal to 2 micrograms/ml) were found in only seven patients out of thirty-six studied. 2. The two conjugates of CPIB found in urine were present in plasma. 3. When measuring conjugated CPIB in plasma it is essential to take care in the handling and storage of specimens, and to select an assay method known to be specific for unmetabolized CPIB.

Clofibrate↗
PubMed1980

Evaluation of the hypolipaemic activity of etofylline clofibrate, a new ester of etofylline and clofibric acid, and comparison with effects of known hypolipaemic agents.

1-(Theophyllin-7-yl)-ethyl-2-[2-(p-chlorophenoxy)-2-methylpropionate] (etofylline clofibrate, ML 1024, Duolip) was compared with several reference compounds for effects on serum cholesterol and triglyceride levels of hypercholesterolaemic rats. ML 1024 appeared to be superior to the reference compounds in reducing cholesterol and triglyceride levels and may have a different mechanism of action to clofibrate.

Animals↗
PubMedDate not supplied

Separation of two conjugates of clofibric acid (CPIB) found in the urine of subjects taking clofibrate.

1. Two main conjugates of CPIB (2-[chlorophenoxy]-2-methylpropionic acid) are present in the urine of subjects taking clofibrate. The metabolites can be separated by thin-layer chromatography (TLC). 2. Both conjugates are hydrolysed by dilute alkali, but only one is hydrolysed by the enzyme beta-glucuronidase. In eighty-five urine specimens this conjugate accounted for an average of 54.5% (range 25-70%) of the total CPIB, while 2.6-12.45% (mean 5.1%) was present as free CPIB.

Chromatography, Gas↗