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The Journal of International Medical... 2002In the present study, we evaluated the effects of combination therapy with niceritrol and pravastatin in patients with hyperlipidaemia. A total of 62 patients with...
In the present study, we evaluated the effects of combination therapy with niceritrol and pravastatin in patients with hyperlipidaemia. A total of 62 patients with hyperlipidaemia, defined as total cholesterol levels above 220 mg/dl or triglyceride levels above 150 mg/dl, were recruited. Patients were divided into two groups: Group N received initial therapy with niceritrol 750-1500 mg/day, and those in Group P, pravastatin 10 mg/day. After 8 weeks, pravastatin 10 mg/day was added to the Group N treatment regimen for a further 8 weeks, while patients in Group P were given niceritrol 750-1500 mg/day in addition to pravastatin for 8 weeks. After the 8-week combination therapy study period, total cholesterol levels were 209.6 mg/dl in Group N and 220.7 mg/dl in Group P. Decreased triglyceride and lipoprotein(a) levels and increased high-density lipoprotein cholesterol levels, neither of which were achieved by pravastatin administration alone, were achieved with the combination of pravastatin and niceritrol. We conclude that when a single lipid-lowering drug fails to show therapeutic value, attempting combination therapy with a nicotinic acid preparation and a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) is worthwhile.
Topics: Cholesterol; Drug Therapy, Combination; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Male; Middle Aged; Niceritrol; Pravastatin; Triglycerides
PubMed: 12166344
DOI: 10.1177/147323000203000308 -
The Tohoku Journal of Experimental... Jun 1984Atherosclerotic lesions were formed in the aorta of rats given a high cholesterol diet containing propylthiouracil (PTU) and vitamin D2 (atherogenic diet) for 8 weeks....
Atherosclerotic lesions were formed in the aorta of rats given a high cholesterol diet containing propylthiouracil (PTU) and vitamin D2 (atherogenic diet) for 8 weeks. The effects of niceritrol (pentaerythritol tetranicotinate), which lower the plasma lipid level, on lipid metabolism in the arterial wall of the atherosclerotic rats were studied. Niceritrol significantly decreased the plasma cholesterol level of atherosclerotic rats, which was 823 mg/100 ml, or about ten times that of control rats. On treatment with niceritrol, the cholesterol level was reduced most in the very low density lipoprotein (VLDL) fraction (d less than 1.006). Heparin-releasable lipoprotein lipase activity in epididymal adipose tissue, lipoprotein lipase activity in post-heparin plasma, and VLDL-triolein hydrolyzing activity in adipose tissue stromal vessels were all higher in niceritrol-treated atherosclerotic rats. Of the enzymes in the arterial wall concerned with cholesterol ester metabolism, acid cholesterol esterase activity was decreased in atherosclerotic rats, while niceritrol treatment increased this activity. The ratio of acyl-CoA cholesterol acyltransferase activity (ACAT) to neutral cholesterol esterase activity was higher in atherosclerotic rats than in control rats, but was lower in niceritrol-treated rats than in atherosclerotic rats. From these results, it is concluded that niceritrol modifies enzyme activities in such a way as to reduce the cholesterol ester content of the arterial wall and lower plasma VLDL and LDL cholesterol levels.
Topics: Adipose Tissue; Animals; Aorta; Arteriosclerosis; Diet, Atherogenic; Lipid Metabolism; Lipids; Lipoprotein Lipase; Lipoproteins; Male; Niceritrol; Nicotinic Acids; Rats; Rats, Inbred Strains
PubMed: 6474452
DOI: 10.1620/tjem.143.231 -
Postgraduate Medical Journal Sep 1988Twenty-five hypercholesterolaemic patients from three centres in the UK were investigated in an open study of the efficacy and side effects of niceritrol. Five patients... (Clinical Trial)
Clinical Trial
Twenty-five hypercholesterolaemic patients from three centres in the UK were investigated in an open study of the efficacy and side effects of niceritrol. Five patients dropped out of the study at an early stage and had insufficient data for analysis. There were 13 males and 7 females (mean age 49.2 years, range 18-69). Fourteen patients had heterozygous familial hypercholesterolaemia, and six polygenic hypercholesterolaemia. Niceritrol was started at a dose of 750 mg/day and this was increased at weekly intervals over 4 weeks to the maximum tolerated dosage up to 3 g/day. This was then maintained for a further 8 weeks. There were statistically significant decreases in total plasma cholesterol, total triglyceride, LDL cholesterol and VLDL triglyceride; HDL cholesterol remained unchanged after 12 weeks of treatment (Wilcoxon matched pairs, signed ranks test). The 14 patients with familial hypercholesterolaemia showed a 13.9% fall in total cholesterol and a 19.8% fall in LDL cholesterol. All patients reported flushing and some had gastrointestinal symptoms but 19 would have been prepared to continue with the therapy at doses up to 3 g/day. Thus niceritrol has been found to be beneficial in the treatment of both familial and polygenic hypercholesterolaemia.
Topics: Adolescent; Adult; Aged; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Drug Administration Schedule; Female; Humans; Hypercholesterolemia; Lipoproteins, VLDL; Male; Middle Aged; Multicenter Studies as Topic; Niceritrol; Nicotinic Acids; Triglycerides; United Kingdom
PubMed: 3075043
DOI: 10.1136/pgmj.64.755.672 -
British Journal of Clinical Pharmacology Jan 1990The usefulness of niceritrol as a lipid-lowering agent is limited by a prostaglandin-mediated flushing reaction after each dose occurring in the early stages of... (Clinical Trial)
Clinical Trial
The usefulness of niceritrol as a lipid-lowering agent is limited by a prostaglandin-mediated flushing reaction after each dose occurring in the early stages of treatment. We have tested the effect of premedication with aspirin on the reaction to 250 mg niceritrol in 30 healthy male volunteers using both subjective and observed assessments of severity. Both 300 mg and 600 mg of aspirin significantly reduced the severity of flushing when compared with placebo. No significant difference was seen between the two dose levels. Prior dosing with aspirin may increase acceptability of niceritrol and hence improve compliance.
Topics: Adolescent; Adult; Aspirin; Flushing; Humans; Male; Middle Aged; Niceritrol; Nicotinic Acids; Random Allocation
PubMed: 2297456
DOI: 10.1111/j.1365-2125.1990.tb03611.x -
Nephron 1997
Clinical Trial
Topics: Blood Coagulation; Female; Fibrinolysis; Humans; Hypolipidemic Agents; Kidney Failure, Chronic; Lipoprotein(a); Male; Middle Aged; Niceritrol; Renal Dialysis
PubMed: 9380227
DOI: 10.1159/000190257 -
The Tohoku Journal of Experimental... Apr 1993The effect of niceritrol at an ordinary dose (1500 mg/day) on the serum lipoprotein(a) (Lp(a)) concentration was investigated in 25 normolipidemic patients with coronary...
The effect of niceritrol at an ordinary dose (1500 mg/day) on the serum lipoprotein(a) (Lp(a)) concentration was investigated in 25 normolipidemic patients with coronary artery disease. The serum Lp(a) level was reduced by approximately 21% after 3 months of treatment (before treatment, 30.3 +/- 4.1 mg/100 ml; during treatment, 22.6 +/- 2.4 mg/100 ml; p < 0.01). By one month after the drug was discontinued, the Lp(a) returned to a pretreatment level (30.8 +/- 2.8 mg/100 ml). The levels of LDL-cholesterol and apoB were decreased significantly by the drug therapy; LDL-cholesterol increased closely to a pretreatment level after withdrawal of the drug. The percentage reduction of Lp(a) was significantly correlated with that of fibrinogen (r = 0.763, p < 0.01). Plasma concentration of fibrinogen was decreased in the patients whose reduction rate of Lp(a) was 30% or more. These results indicate that niceritrol has Lp(a)-lowering effect; sufficient reduction of Lp(a) may improve dyscoagulopathy of patients with coronary artery disease.
Topics: Adult; Aged; Apolipoproteins; Apolipoproteins B; Cholesterol, LDL; Coronary Disease; Female; Fibrinogen; Humans; Hypolipidemic Agents; Lipoprotein(a); Male; Middle Aged; Niceritrol; Regression Analysis
PubMed: 8248919
DOI: 10.1620/tjem.169.299 -
Kidney International. Supplement Jul 1999Patients with chronic renal failure often have alterations in lipoprotein profile including elevated very-low density lipoprotein (VLDL) and intermediate density...
BACKGROUND
Patients with chronic renal failure often have alterations in lipoprotein profile including elevated very-low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL), and reduced high density lipoprotein (HDL) levels. Among these changes, raised IDL has been shown as an independent risk factor for atherosclerosis in hemodialysis patients. There are a limited number of studies reporting pharmacological approaches to IDL reduction in a uremic population.
METHODS
We therefore summarize the effects of lipid-lowering drugs on IDL levels in patients with chronic renal failure treated by hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD).
RESULTS
First, a nicotinic acid analog niceritrol was given to hemodialysis patients. The drug increased HDL-cholesterol by 11%, but the reductions in VLDL-, IDL- and LDL-cholesterol were not significant. Second, CAPD patients were treated with a fibric acid derivative clinofibrate, which was excreted mainly into bile unlike other drugs in this class. The fibrate resulted in a remarkable reduction in VLDL-triglycerides, although it did not reduce IDL-cholesterol. Finally, an HMG-CoA reductase inhibitor (statin) pravastatin was used in HD and CAPD patients. Pravastatin reduced IDL- and LDL-cholesterol to the same extent (by 31%). None of these treatments caused serious adverse effects.
CONCLUSIONS
We propose that IDL is an important target in the management of uremic dyslipidemia. To date, statins have been shown to be suitable for this purpose, although it remains to be clarified whether such an intervention reduces the risk for atherosclerotic vascular events in the uremic population.
Topics: Cholesterol, LDL; Cholesterol, VLDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Lipoprotein(a); Lipoproteins; Lipoproteins, VLDL; Niceritrol; Peritoneal Dialysis, Continuous Ambulatory; Phenoxyacetates; Pravastatin; Renal Dialysis; Uremia
PubMed: 10412757
DOI: 10.1046/j.1523-1755.1999.07133.x -
Annals of the Rheumatic Diseases Feb 1995To investigate if serum Lp(a) lipoprotein (Lp(a)), a risk factor for atherosclerotic diseases, increases in patients with gout, who frequently also have atherosclerotic... (Comparative Study)
Comparative Study
OBJECTIVES
To investigate if serum Lp(a) lipoprotein (Lp(a)), a risk factor for atherosclerotic diseases, increases in patients with gout, who frequently also have atherosclerotic disease.
METHODS
Fasting blood samples were taken for measurement of Lp(a) and other variables in 175 male patients with primary gout. Serum concentrations of Lp(a) were measured by enzyme linked immunosorbent assay. The median value and frequency distribution of Lp(a) in gout patients were compared with those in 172 control male subjects. In addition, we examined the effect of niceritorol on serum Lp(a) values in gout patients in whom the Lp(a) concentration was greater than 20 mg/dl.
RESULTS
Serum Lp(a) was significantly higher in patients with gout than control subjects (median 15.5 mg/dl upsilon 8.6 mg/dl; p < 0.01). The frequency distribution of Lp(a) in gout was significantly shifted towards greater concentrations compared with control, although skewed distribution was noted in both groups. Serum Lp(a) concentration was not related to age, body mass index, alcohol intake, creatinine, fasting blood sugar or uric acid in patients with gout. Niceritorol decreased the serum concentrations of Lp(a) in gout.
CONCLUSIONS
These observations suggest that serum Lp(a) concentrations are increased in patients with gout and may play a role as one of the risk factors for atherosclerotic diseases in gout. Niceritorol seems effective in decreasing high levels of Lp(a) in patients with gout without detrimental influence on serum uric acid concentration.
Topics: Adult; Aged; Aged, 80 and over; Apolipoproteins B; Arteriosclerosis; Cholesterol, HDL; Enzyme-Linked Immunosorbent Assay; Gout; Humans; Lipoprotein(a); Male; Middle Aged; Niceritrol; Risk Factors; Triglycerides
PubMed: 7702412
DOI: 10.1136/ard.54.2.90 -
Endocrine Journal Dec 2006The patient was a 51-year-old Japanese female who had been diagnosed with hyperlipidemia. At the first medical examination, her serum levels of total cholesterol (TC)...
The patient was a 51-year-old Japanese female who had been diagnosed with hyperlipidemia. At the first medical examination, her serum levels of total cholesterol (TC) and triglyceride (TG) were 482 and 205 mg/dl, respectively. Since hyperlipidemia was not improved by pravastatin, atorvastatin or niceritrol, and since the levels of thyroid-stimulating hormone (TSH) and free T4 were 730 IU/ml and 0.3 ng/dl, respectively, the patient was diagnosed as secondary hyperlipidemia with hypothyroidism. A method for the charge isolation of lipoproteins using capillary isotachophoresis (cITP) is proposed as a clinical application because it allows us to quantitatively measure electronegative low-density lipoprotein cholesterol (LDL-C), a potent marker of coronary heart disease. After 5 months of treatment with levothyroxine, Serum TC and LDL-C levels drastically decreased without statin treatment and high-density lipoprotein cholesterol (HDL-C) increased. In the lipoprotein profiles as assessed by cITP after treatment with levothyroxin, all HDL-C subfractions were increased and fast-migrating LDL/electronegative LDL appeared to be greatly reduced after treatment, while the area under the non-modified LDL peak was increased. The cITP analysis was able to obtain more information about coronary risk factors and may be clinically useful for evaluating the effect of treatment with levothyroxine in patients with hypothyroidism and secondary hyperlipidemia.
Topics: Electrophoresis, Capillary; Female; Humans; Hyperlipidemias; Hypothyroidism; Lipids; Lipoproteins; Middle Aged; Thyroxine
PubMed: 17001111
DOI: 10.1507/endocrj.k05-181