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Biomedical subjects

P D Lang

Publications and source records attributed to P D Lang.

At least 19 recordsLinked to original sources

A double-blind comparison of the effects of carvedilol and captopril on serum lipid concentrations in patients with mild to moderate essential hypertension and dyslipidaemia.

We have studied 250 patients with mild to moderate essential hypertension (diastolic blood pressure 95-114 mmHg) and dyslipidaemia (high-density lipoprotein cholesterol (HDL-C) below 1.03 mmol.l-1, total cholesterol 5.17-9.05 mmol.l-1, and triglycerides 2.26-5.64 mmol.l-1) in a controlled double-blind, multicentre, parallel group trial. The patients took a fat-modified diet. After a 4-week placebo period, patients who continued to fulfil the selection criteria were randomly allocated to treatment with either carvedilol (a vasodilating beta-blocker) 25-50 mg o.d. (n = 116) or captopril (an ACE inhibitor) 25-50 mg o.d. (n = 117) for 6 months. In both groups there were favourable effects on the serum lipids. The relative changes (medians) in the carvedilol and captopril group were respectively: increase in HDL-C by 11% and 8%, decrease in total cholesterol by 11% and 10%, in low-density lipoprotein cholesterol by 16% and 12%, and in triglycerides by 13% and 14%. Equivalence of the two treatments was confirmed for the target variable change in HDL-C at a significance level of 5%. Reductions in supine systolic/diastolic blood pressures were comparable in the two groups (carvedilol: 23/19 mmHg, captopril: 20/18 mmHg). The improvement in lipid metabolism in patients treated with carvedilol is probably due to its alpha 1-blocking properties.

Adult↗

Efficacy of a combined bezafibrate retard-colestyramine treatment in patients with hypercholesterolemia.

In a placebo-controlled randomized study the effect of combined bezafibrate-colestyramine therapy in comparison with monotherapy with both drugs was investigated. 47 patients with primary hypercholesterolemia received 400 mg bezafibrate (Cedur) retard/d, subsequently bezafibrate retard plus colestyramine (24 g/d) or colestyramine plus placebo in a double-blind fashion. The combination therapy was most effective (LDL decrease 36%, HDL-C increase 31%, apoprotein B decrease 28%), bezafibrate and colestyramine were equally effective with regard to LDL-C and apoprotein B, but only bezafibrate decreased triglycerides (-37%) and increased HDL-C (+24%). Bezafibrate was well-tolerated, but gastro-intestinal side-effects were frequent during therapy with colestyramine, and 16 patients tolerated only a reduced dosage of this drug. From the results presented it can be concluded that combined therapy with bezafibrate retard plus colestyramine is highly effective in the treatment of severe hypercholesterolemia.

Bezafibrate↗

Effects of a bezafibrate sustained release formulation on plasma lipoproteins in patients with hypercholesterolemia. Importance of timing of tablet intake for efficacy.

The therapeutic effect of a single sustained release tablet of bezafibrate (Cedur retard, 400 mg) in primary hypercholesterolemia type IIa and type IIb was investigated in a placebo-controlled randomised study comparing the efficacy of morning vs. evening intake. The decrease in total cholesterol with the morning intake was 18.5% vs. 16.5% for the evening intake (n.s.). HDL-cholesterol increased more in patients taking bezafibrate retard at morning (29.6% vs. 22.4%, p less than 0.05). Bezafibrate was well tolerated. Animal experiments and precursor studies of cholesterol synthesis in man indicate peak activity of HMG-CoA reductase between 1 a.m. and 3 a.m. The data suggest that with normal eating habits during day time other modes of action of bezafibrate besides HMG-CoA reductase inhibition such as reduction of VLDL-synthesis in the liver and an increased fractional catabolic rate, could contribute to the therapeutic effect.

Alkaline Phosphatase↗

Effect of bezafibrate and colestyramine in patients with primary hypercholesterolemia.

40 patients with primary hypercholesterolemia were included in a randomized cross-over trial comparing effects and tolerance of bezafibrate (Cedur) (200 mg t.i.d.) and colestyramine (4 g t.i.d.). Gastrointestinal side-effects led to the discontinuation of colestyramine in 11 patients. No adverse events were observed with bezafibrate. Both drugs had similar effects on total and low density lipoprotein cholesterol (bezafibrate: -15% and -12%, respectively; colestyramine: -10% and -11%, respectively). While the high density lipoprotein-increasing effect of bezafibrate was more marked (+20% vs. +14%), triglycerides and very low density lipoprotein cholesterol were lowered by bezafibrate (-22% and -27%, respectively) and tended to increase with colestyramine (+11% and +10%, respectively). In the light of results of a multicenter primary prevention trial bezafibrate also should have a protective effect on coronary heart disease. This, however, has to be proven in longterm prospective trials.

Bezafibrate↗

Lipid lowering treatment with bezafibrate in patients on chronic haemodialysis: pharmacokinetics and effects.

Hyperlipidaemia may contribute to the high rate of cardiovascular complications in patients on chronic haemodialysis (CHD). However, possibilities of lipid lowering therapy in CHD are still limited. The applicability of bezafibrate (BF), a recently developed clofibrate analogue, was investigated in patients on CHD with triglyceride and/or total cholesterol levels above 300 mg/dl. The lipid lowering effect was studied in a placebo-controlled trial over 6 months in 19 patients. Long-term effect was followed in six patients over a mean period of 29 months. Elimination half-life and mean therapeutic serum concentration were calculated by 72-h BF serum profiles, obtained after the first drug administration of a single 200-mg dose and during steady state after 12 weeks of treatment. Elimination half-lives were 17 h at start and 22 h after 12 weeks compared with 2 h in subjects with normal renal function. Dose reduction to 200 mg every 3rd day was necessary and resulted in a mean therapeutic serum concentration of 3.4 mg/l, which was similar to 3.0 mg/l of normal subjects, who received the dose optimal for lowering of lipids (200 mg 3 X/day). The protein-bound serum fraction of BF was decreased to 8% in CHD patients, compared with 95% found in normal subjects. BF therapy resulted in a marked reduction of serum triglycerides from 478 mg/dl by 31% and total cholesterol levels from 311 mg/dl by 19% as well as beta-Lp-cholesterol from 178 mg/dl by 17%, whereas the initially low alpha-Lp-cholesterol increased significantly from 18.3 mg/dl by 58%.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Diurnal lipid and lipoprotein profiles in hypertriglyceridemic patients with bezafibrate and clofibrate.

Thirty hypertriglyceridemic patients were treated under metabolic ward conditions for 10 days with either placebo, clofibrate (500 mg t.i.d.) or bezafibrate (200 mg t.i.d.) in a randomized, double-blind study. In addition, patients received an isocaloric prudent diet. On day 10 a diurnal lipid and lipoprotein profile was carried out. Compliance to medication was good. Each treatment led to significant reductions of fasting triglycerides and cholesterol. Lowering of fasting and integrated diurnal triglycerides was greatest with bezafibrate. HDL-cholesterol profiles were highest with this drug. A strong correlation between fasting and diurnal triglycerides was observed. Triglyceride-lowering therapy must therefore aim at fasting triglyceride values as low as possible.

Adult↗

Effect of bezafibrate during 4.5 years of treatment of hyperlipoproteinaemia.

Bezafibrate in a dosage of 200 mg 3 times daily was given to 24 patients with type II A (n = 8), II B (n = 1) and IV (n = 15) hyperlipoproteinaemia for 4.5 years. In type II A the content of total cholesterol and that of low density lipoprotein in serum decreased by 10-23 and 11-34 percent over the years compared to pretreatment. In type IV the content of total triglycerides and that of very low density lipoprotein decreased by 28-39 and 38-52 percent, respectively, over the years. High density lipoprotein cholesterol increased in both types. The "atherogenic index" was reduced by the drug. The effect remained through the 4.5 years of treatment. Compliance to the drug was good. Changes in safety laboratory parameters were minor and reversible. No subjective side-effects occurred and no cases of gallbladder disease or cancer were noted. It is concluded that bezafibrate is a safe, convenient and effective serum lipid-lowering drug suitable for the use in primary and secondary prevention of atherosclerotic disease.

Bezafibrate↗

Diurnal lipid and lipoprotein profiles with bezafibrate and clofibrate in healthy volunteers.

Diurnal lipid and lipoprotein profiles were measured in 28 healthy volunteers after 10-day treatment periods with placebo, bezafibrate (200 mg 3-times daily) or clofibrate (500 mg 3-times daily) in a double-blind, parallel trial. The two drugs lowered fasting triglyceride and cholesterol levels (p less than or equal to 0.05 for cholesterol with bezafibrate vs placebo). Diurnal triglyceride profiles were lowest with bezafibrate due to lowest fasting triglycerides. Alimentary lipaemia with placebo was mild and due to increased VLDL-triglycerides, while the other lipoprotein lipids and total plasma cholesterol remained virtually unchanged during the day. Bezafibrate (half-life 2 hours) and clofibrate (half-life 15 hours) gave similar diurnal triglyceride patterns. The diurnal values were dependent on the fasting values. Changes in the cholesterol/phospholipid ratio during the day may be related to altered post-prandial composition of HDL.

Adult↗

Fatty acid composition of adipose tissue, blood, lipids, and glucose tolerance in patients with different degrees of angiographically documented coronary arteriosclerosis.

Forty-eight patients with symptoms of angina pectoris were studied for adipose tissue fatty acid composition and cardiovascular risk factors while hospitalized for selective coronary angiography. Patients with manifest diabetes mellitus and deviations form the "normal" customary diet were excluded. Pairwise comparison between the groups with absent, slight, moderate, and severe coronary arteriosclerosis showed reasonable comparability for age, relative body weight, and skinfold measurements. The proportion of smokers, but not of hypertensives, showed a significant positive relationship with the degree of arteriosclerosis. Serum cholesterol was similar in all four groups, while triglycerides were clearly, but not significantly (P greater than 0.05) higher in patients with coronary arteriosclerosis. The oral glucose tolerance test (OGTT) index was significantly higher in moderate and severe disease. Significantly higher proportions for palmitic acid lower proportions for linoleic acid were also found in these two groups. Multiple linear regression analysis showed a positive association with coronary arteriosclerosis for: OGTT index greater than palmitic acid greater than arachidonic acid greater than triglycerides. The close negative association between the proportion of stearic acid in adipose tissue and coronary heart disease observed in two previous studies could not be confirmed. On the basis of the present study, stearic acid correlates with age rather than with arteriosclerotic disease.

Adipose Tissue↗

Bezafibrate: lack of effect on creatinine excretion and muscular proteins.

The effect of bezafibrate (200 mg t.i.d.) on renal and, to some degree, on muscular function was studied in nine patients with primary hyperlipoproteinemia. No signs of a reduction in creatinine excretion or an increase in muscular proteins could be found serving as a possible explanation for the slight increase in serum creatinine observed in a bezafibrate long-term study in more than 1,000 patients. Further studies are necessary for clarification.

Bezafibrate↗

Reduced LDL- and increased HDL-apoproteins in patients with hypercholesterolaemia under treatment with bezafibrate.

The effect of bezafibrate on serum lipids, lipoproteins and the apoproteins A-I, A-II and B was studied in 18 patients with primary hypercholesterolaemia. Total cholesterol was lowered by 20% (P less than 0.05), LDL-cholesterol by 24% (P less than 0.05), and apo B by 14% (P less than 0.05), which is comparable to the effect obtained with anion exchange resins but with far fewer side-effects. HDL increased significantly during bezafibrate treatment both by measurement of HDL-cholesterol (+54%, P less than 0.05) and by the determination of HDL-apoproteins A-I (+ 19%, P less than 0.05) and A-II (+ 23%, P less than 0.05). This increase of HDL and the decrease of triglycerides was maintained for 6 weeks of placebo treatment after cessation of bezafibrate, while serum total and LDL cholesterol as well as apo B returned to their baseline levels.

Adult↗

[Dose-effects studies with bezafibrate in patients with hypercholesterolemia and hypertriglyceridemia (author's transl)].

The dose-effect relationship of bezafibrate, a new clofibrate derivative, was investigated in 24 outpatients with a primary hyperlipidemia and a Type lla lipoprotein pattern. The patients were divided into two groups at random and in each case received 3 X 50, 3 X 100, 3 X 150 and 3 X 200 mg bezafibrate daily in increasing or falling dosage for four weeks. For rising doses a statistically significant dose-effect relationship could be demonstrated for cholesterol and triglycerides. This was only true for cholesterol with falling doses while triglycerides remained at a low level. The optimal dose was found to be 600 mg bezafibrate daily. The substance was well tolerated, and the usual laboratory parameters remained within the normal range in all patients.

Cholesterol↗

[Comparison of clofibrate and bezafibrate in type IIa and type IIb hyperlipoproteinemia].

In a randomized block-trial the comparative efficacy and side-effects of clofibrate (2 X 1 g), placebo and bezafibrate (3 X 150 mg) were tested in groups of 24 patients each with hyperlipoproteinemia type IIa and IIb. Each period of treatment was 2 months. Both bezafibrate and clofibrate as compared to placebo were associated with a significant lowering of triglycerides and cholesterol: triglycerides by 30% in type IIa and a 41% reduction in type IIb, whereas clofibrate lowered triglycerides by 23% in type IIa and 28% in type IIb. Bezafibrate reduced total cholesterol by 18% in type IIa and 12% in type IIb as opposed to clofibrate reducing cholesterol by 16% in type IIa and 8% in type IIb. Bezafibrate compared to clofibrate was shown to be significantly more effective in lowering triglycerides in type IIa correlating to a significant reduction of VLDL- and LDL-triglycerides in this type. Both substances significantly lowered LDL-cholesterol in type IIa; in type IIb only bezafibrate was effective. HDL-cholesterol increased significantly with bezafibrate. The effect of clofibrate raising LDL-cholesterol in dependence on the initial concentration of the VLDL-triglycerides was seen less frequently after bezafibrate and only with higher initial VLDL-concentrations as compared to clofibrate. Patients tolerated both bezafibrate and clofibrate equally well. It should be considered that bezafibrate was not given in the optimal dose of 3 X 200 mg.

Adult↗