Disease relevance of pravastatin

• Therefore, we studied the lipid-lowering efficacy and safety of pravastatin sodium (20 mg/d), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in 245 African-American patients with primary hypercholesterolemia [1].
• Six of these animals also received pravastatin sodium at a daily dose of 1 mg/kg body weight (verum group) [2].
• Suppression of established atherosclerosis and xanthomas in mature WHHL rabbits by keeping their serum cholesterol levels extremely low. Effect of pravastatin sodium in combination with cholestyramine [3].
• Drug-based solutions to the obesity problem that work with the lipostat, rather than against it, are presently under development and will probably be in regular use within 5-10 y [4].
• Crystallization and preliminary X-ray diffraction analysis of cytochrome P450sca-2 from Streptomyces carbophilus involved in production of pravastatin sodium, a tissue-selective inhibitor of HMG-CoA reductase [5].

Psychiatry related information on pravastatin

• Leptin has emerged as the major lipostat, regulating adiposity by affecting feeding behavior and thermogenesis [6].

High impact information on pravastatin

• Consistently, the cholesterol-lowering agent (pravastatin sodium) downregulated the expression of RALDH1 and 2 genes in several organs especially the liver and in cultured liver cells [7].
• Leptin, secreted from fat cells, functions as a lipostat mechanism through modulation of satiety signals [8].
• Effect of pravastatin on angiographic restenosis after coronary balloon angioplasty. The PREDICT Trial Investigators. Prevention of Restenosis by Elisor after Transluminal Coronary Angioplasty [9].
• Disorders of GH secretion are known to impair the physiological lipostat and to affect the secretion of leptin, a sensitive marker of regional fat accumulation and total body composition [10].
• Thus, the cross-talk between the thyrostat and the lipostat might play a crucial role in the maintenance of body homeostasis [11].

Chemical compound and disease context of pravastatin

• Purification and characterization of cytochrome P-450sca from Streptomyces carbophilus. ML-236B (compactin) induces a cytochrome P-450sca in Streptomyces carbophilus that hydroxylates ML-236B to pravastatin sodium (CS-514), a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase [12].

Biological context of pravastatin

• From the results, we conclude that administration of pravastatin sodium, but not simvastatin, reduced the plasma fibrinogen level and blood viscosities to normal levels in type II hyperlipoproteinemic patients while both drugs reduced total cholesterol level [13].
• Biotransformation of pravastatin sodium in humans [14].
• Cytochrome P450sca-2 from Streptomyces carbophilus catalyzes the hydroxylation of ML-236B sodium salt to pravastatin sodium, a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl-coenzymeA (HMG-CoA) reductase [5].
• Leptin is secreted from adipose tissue, and is thought to act as a 'lipostat', signalling the body fat levels to the hypothalamus resulting in adjustments to food intake and energy expenditure to maintain body weight homeostasis [15].
• Effects of short-term treatment with mevalotin on platelet aggregation, fibrinolysis, peripheral serotonergic system and serum lipids in Japanese monkeys [16].

Anatomical context of pravastatin

• Pravastatin sodium was gavaged at 0.4 mg per kg per day for 5 days, after which LPS 15 mg/kg was administered via the jugular vein [17].
• Effects of different inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, pravastatin sodium and simvastatin, on sterol synthesis and immunological functions in human lymphocytes in vitro [18].
• 3. One of the synthetic epoxides, 4'a beta, 5' beta-epoxide was converted to the pravastatin metabolite, 4'a alpha-glutathione conjugate (CM-1) by a rat liver cytosol system and is proposed as the common metabolic intermediate between pravastatin sodium and the metabolites, CM-1 and CM-2 [19].
• On the other hand, the inhibition by CS-514 was much less in the cells from nonhepatic tissues such as freshly isolated rat spleen cells, and cultured mouse L cells and human skin fibroblasts [20].

Associations of pravastatin with other chemical compounds

• Biotransformation of pravastatin sodium (I). Mechanisms of enzymic transformation and epimerization of an allylic hydroxy group of pravastatin sodium [21].
• The plasma triglyceride lowering effect of the five statin drugs tested produced the following rank order; pravastatin sodium (-44%)>atorvastatin calcium (-36%)>simvastatin (-33%)>lovastatin (-25%)>fluvastatin sodium (-19%) [22].
• A marked increase in hepatic hydroxymethylglutaryl-CoA reductase activity in vitro and also an increased de novo cholesterol synthesis in the liver were induced by treatment with CS-514 for 1-4 weeks [23].
• Cerebral blood flow velocity (CBFV) increase after bolus injection of 1 g acetazolamide was determined before and after 2-month treatment with pravastatin sodium 20 mg daily [24].
• Male golden hamsters fed a glucose diet as a model for cholesterol gallstone formation were used to investigate the effect of CS-514 on the lithogenicity of bile [23].

Gene context of pravastatin

• Four groups of subjects were treated with the HMG-CoA reductase inhibitor pravastatin (Pravachol), 20 mg twice daily for 12, 24, 48 and 72 h preoperatively [25].
• These results suggest that inhibition of de novo cholesterol synthesis by CS-514 enhanced LDL receptor function in primary cultures of rat hepatocytes and lowered LDL-cholesterol level [26].
• Long-term treatment of hypercholesterolemic non-insulin dependent diabetics (NIDDM) with pravastatin (CS-514) [27].
• We attempted to determine whether inhibition of microsomal HMG-CoA reductase by pravastatin sodium would yield similar values for the maximum reaction in velocity (Vmax) and the HMG-CoA reductase-pravastatin dissociation constant (Ki) when the enzyme was in the activated state compared with the control state [28].
• Thus, CS-514 reduces atherogenic lipoproteins and apolipoprotein B, and increases HDL and apolipoprotein A-I and A-II, and appears to be a useful drug for heterozygous familial hypercholesterolemia [29].

Analytical, diagnostic and therapeutic context of pravastatin

• We conclude that pravastatin sodium reduces total plasma cholesterol levels in this animal model, thereby leading to smaller plaques and a different plaque type [2].
• After more than 3 procedures of LDL-apheresis without drug therapy, combination therapy with LDL-apheresis and CS-514 (eptastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme (HMG-CoA) reductase, at a dose of 10 mg twice daily was started [30].
• METHODS: In the first experiment, rabbits were randomized to a control group (n = 7) that was fed regular rabbit chow or to a pravastatin group (n = 7) that was fed regular rabbit chow supplemented with 10 mg/kg pravastatin sodium [31].
• Highly sensitive and specific determination of pravastatin sodium in plasma by high-performance liquid chromatography with laser-induced fluorescence detection after immobilized antibody extraction [32].
• Determination of pravastatin sodium and its isomeric metabolite in human urine by HPLC with UV detection [33].

References