Treatment Of Hyperlipoproteinaemia Research Articles

Metabolic fate of pitavastatin (NK-104), a new inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase. Effects on drug-metabolizing systems in rats and humans.

Pitavastatin (CAS 147526-32-7, NK-104) is a new and very potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and has been approved for treatment of hyperlipoproteinaemia. Pitavastatin has been studied for its effects on hepatic microsomal drug metabolism in rats, and the activities of several drug-metabolizing enzymes have been measured. No induction of the drug metabolizing enzymes (aniline hydroxylase, aminopyrine N-demethylase, 7-ethoxycoumarin O-deethylase and UDP-glucuronic acid transferase) was found in the pitavastatin group compared to the control after the multiple administrations of pitavastatin at the dosage of 1-10 mg/kg per day for 7 days. Based on several different in vitro approaches, it is concluded that CYP2C9 is the enzyme responsible for the metabolism of pitavastatin and no metabolite is present in renal and intestinal microsomes. The CYP2C9 polymorphism was not involved in the pitavastatin metabolism. No inhibitory effect in CYP-mediated metabolism was detected on the tolbutamide 4-hydroxylation (CYP2C9) and testosterone 6 beta-hydroxylation (CYP3A4) in the presence of pitavastatin. The results suggested that pitavastatin did not affect the drug-metabolizing systems.

Clinical evaluation of homoeopathic therapy in the management of hyperlipoproteinemia

Objectives: This study aimed at evolving a group of useful homoeopathic medicines in the treatment of hyperlipoproteinaemia, to identify their reliable indications, most useful potencies, frequency of administration and relationship with other medicines. Methods: A prospective observational study was carried out during the period 1992-2003. Three hundred and twenty two patients with hyperlipoproteinaemia and various clinical presentations were studied. Patients of more than 30 years of age, with cholesterol > 200mg/dl, triglycerides > 170mg/dl, LDL > 150mg/dl, VLDL > 50mg/dl and HDL < 35 mg/dl were included in this study. Specific parameters were followed to assess the intensity of complaints and the improvement status. Homoeopathic medicines were prescribed in different potencies (Q to 10M), basing on the presenting complaints, mental and physical attributes of the patients. The patients were advised to have low calorie diet and regular exercise. Results: Two hundred ninety three (293) patients were followed up regularly and varying degrees of improvement were observed, viz. marked improvement in 77 patients, moderate improvement in 113 patients, mild improvement in 100 patients and no improvement in 03 patients. Abroma augusta 30, Gelsemium 30, Lycopodium 1M, Bryonia alba 30, Pulsatilla 30, Nux vomica 30 were found to be useful among the other prescribed medicines. Conclusion: Results obtained from the study are encouraging with findings that 26% of the patients improved markedly with an evidence of changes in laboratory parameters. However, an experiment in controlled setting with improved protocol and clearer outcome parameters is required.

Encouraging findings for artichoke extract in the treatment of hyperlipoproteinaemia

Encouraging findings for artichoke extract in the treatment of hyperlipoproteinaemia

Application of granulated apple pectin in the treatment of hyperlipoproteinaemia

The dynamics of the impact of highly esterified apple pectin on lipid metabolism by humans was studied. The experiments involved 109 patients (54 women and 55 men) with hyperlipoproteinaemia. The lipid metabolism of 73 healthy persons (35 men and 38 women) and 36 persons (17 men and 19 women) with hyperlipoproteinaemia was investigated as a control. A granulated form of a mixture of pectin and sorbitol in a ratio of 2:1 was used. The results confirmed the favourable effect of apple pectin on the major characteristics of lipid metabolism by humans: the levels of serum cholesterol, high-density lipoprotein-cholesterol and triglycerides. Sorbitol manifests synergism regarding the hypolipidaemic effect of pectin. It was established that the model y=x(A+Bx), where x is time and y the parameter under investigation, best explained the dynamics of the studied characteristics of lipid metabolism under the impact of granulated highly esterified apple pectin. (A and B are experimental constants).

Disturbances of lipid metabolism in children with chronic renal failure

This review discusses the pathogenesis, clinical significance and current therapy of hyperlipoproteinaemia (HLP) in children with chronic renal failure. Uraemic dyslipidaemia, characterized by hypertriglyceridaemia and low high-density lipoprotein-cholesterol levels, is present in the majority patients with chronic renal failure. In addition, serum levels of total cholesterol, very low-density lipoprotein-cholesterol, low-density lipoportein-cholesterol and apolipoprotein B are frequently elevated. The pathophysiological mechanisms causing these disturbances are complex and mainly involve a diminished catabolism of triglyceride-rich lipoproteins. For unknown reasons and independent of other lipoproteins, serum levels of the highly atherogenic and thrombogenic lipoprotein(a) are also often elevated. HLP is an important factor in cardiovascular morbidity and mortality. In addition, dyslipidaemia may enhance progression of renal disease in patients with residual renal function. Therefore, treatment of HLP seems indicated in overtly hyperlipidaemic patients, but until there is more experience with lipid-lowering drugs in children, no safe recommendations for pharmacological treatment of HLP can be given. Dietary modifications can be recommended only to a limited extent.

Effects of simvastatin, a lipoprotein-lowering drug, on the hepatic enzymes involved in drug metabolism in the Wistar rat

1. Simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl CoA reductase, lowers the plasma cholesterol level and has been approved for treatment of hyperlipoproteinaemia. 2. Simvastatin has been studied for its effects on hepatic microsomal drug metabolism in rat. No induction of 7-ethoxyresorufin-O-deethylase (EROD), ethoxycoumarin-O-deethylase (ECOD) and of UDP-glucuronosyltransferases were found, in vitro, after administration of 0.5, 1.5 and 10 mg/kg per day for 22 days. 3. Epoxide hydrolases (microsomal and cytosolic) were also unchanged after treatment with simvastatin. 4. No increase of the palmitoyl CoA oxidase activity or of mitochondrial glycerol phosphate dehydrogenase activity occurred. 5. Fatty acid distribution in rat liver microsomal phosphatidylcholines showed a significant decrease of C16:1 and a significant increase of C20:4 acids.

Limb blood flow in treated hyperlipoproteinaemic patients with peripheral vascular disease: A preliminary report

Fourteen patients with hyperlipoproteinaemia and peripheral vascular disease have been investigated to determine the effect on limb blood flow of hypolipidaemic therapy. Satisfactory lowering of serum lipoprotein levels was achieved in the treated group. There was a significant deterioration in peak reactive blood flow measurements in the placebo group compared with the treated group. Treatment of hyperlipoproteinaemia may, therefore, be of value in preventing the progression of peripheral atherosclerosis.

On the rise in low density and high density lipoproteins in response to the treatment of hypertriglyceridaemia in type IV and type V hyperlipoproteinaemias

In Type V hyperlipoproteinaemia the concentration of LDL and HDL cholesterol is low. When the hypertriglyceridaemia is normalized, either by diet or nicotinic acid, both LDL and HDL increase. In Type IV hyperlipoproteinaemia both LDL and HDL cholesterol decrease with increasing VLDL levels. During treatment of Type IV the change in LDL cholesterol is linearly related to the pretreatment LDL concentration so that higher LDL levels will fall and the lower will rise. HDL levels will also rise. The fall in VLDL during treatment is rapid and the rise in LDL also occurs rapidly indicating a relationship between these two reciprocal changes. HDL cholesterol, however, remains constant some time after VLDL has reached its lowest level and the rise occurs later indicating another mechanism than for LDL. These changes in the three major lipoprotein classes deserve clinical attention. While both the fall in VLDL and the rise in HDL may be benefical from the point of view of atherosclerosis the rise in LDL may be harmful. There is at present no way to evaluate the effect of these complex changes. However, these findings stress the imporance of considering changes in lipoprotein levels and not only in total serum triglycerides and cholesterol during treatment of hyperlipoproteinaemia.