ロバスタチン 化学特性,用途語,生産方法
外観
白色～ほとんど白色, 結晶～粉末又は塊
溶解性
本品1mg+エタノール(99.5)1mlに全溶エタノール及びアセトンに溶け、水にほとんど溶けない。
用途
病理研究用、昆虫神経ペプチド類の作用機構の研究用。
効能
脂質異常症治療薬, HMG-CoA還元酵素阻害薬
説明
Lovastatin is an orally-active hypocholesterolemic useful in the treatment of familial
hypercholesterolemia. The drug acts by inhibiting the HMG-CoA reductase-catalyzed rate
limiting step of cholesterol biosynthesis. While treatment with lovastatin leads to
significant reductions in total and LDL cholesterol, its effect on atherosclerosis or
coronary heart disease has not been established.
化学的特性
White Solid
物理的性質
Appearance: White, nonhygroscopic crystalline powder. Solubility: Insoluble in
water (0.0004?mg/mL); sparingly soluble in ethanol, methanol, isobutanol, isopropanol, acetonitrile, n-propanol; soluble in acetone, N-dimethylformamide; freely
soluble in chloroform. Melting point: 174.5?°C. Specific optical rotation: 25?°C for
D (sodium) line, +323° (concentration 0.5? g in 100? ml acetonitrile). Stability:
Lovastatin is sensitive to light. Following exposure to extreme light conditions, the
drug is stable for 24?h or 1?month when exposed to UV (approximately 3230 lux) or
fluorescent (approximately 10,764 lux) light, respectively, at 28?°C in air.
来歴
Statins are the most extensively used class of lipid-lowering medication. Lovastatin
is the second statin discovered by scientists.
Later, the official name lovastatin was established. The activity of lovastatin is
much better than compactin.
In July 1982, lovastatin showed dramatic effects on lowering LDL cholesterol in
patients with severe hypercholesterolemia who were unresponsive to the existedmedicines, with very few adverse reactions .
使用
Lovastatin (mevinolin) is a metabolite first isolated from Monascus ruber and later found in several other fungal species. Lovastatin is a potent inhibitor of HMG-CoA. HMG-CoA reductase is the rate-controlling enzyme of the mevalonate pathway, responsible for the biosynthesis of cholesterol. Lovastatin was developed as a drug as a hypolipemic agent.
適応症
Hypercholesterolemia, combined hyperlipidemia.
一般的な説明
Lovastatin, 2-methylbutanoic acid 1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy6-oxo-2H-pyran-2-yl)ethyl]-1-naphthalenyl ester, mevinolin,MK-803 (Mevacor) (formerly called mevinolin), is a potentinhibitor of HMG-CoA. The drug was obtained originallyfrom the fermentation products of the fungi Aspergillus terreusand Monascus ruber. Lovastatin was one of two originalHMG-CoA reductase inhibitors. The other drug, mevastatin(formerly called compactin), was isolated from cultures ofPenicillium cillium citrum. Mevastatin was withdrawn fromclinical trials because it altered intestinal morphology in dogs.This effect was not observed with lovastatin. For inhibitoryeffects on HMG-CoA reductase, the lactone ring must be hydrolyzedto the open-ring heptanoic acid.
生物活性
Potent, competitive inhibitor of HMG-CoA reductase (K i = 0.6 nM) therefore decreases cholesterol biosynthesis, in vitro and in vivo . Decreases CDK2, 4, 6 and cyclin E levels and induces G1 arrest and apoptosis in tumor cell lines in vitro .
薬理学
Lovastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase
(HMG-CoA reductase), an enzyme that catalyzes the conversion of HMG-CoA to
mevalonate , a rate-determining step of cholesterol biosynthesis. Lovastatin is
metabolized as a prodrug into an active form, lovastatin acid. Lovastatin acid is a
reversible competitive inhibitor for HMG-CoA.
However, the reduction in plasma cholesterol by statins is not only due to reduction in cholesterol biosynthesis. .
In addition to their lipid-lowering properties, statins produce several nonlipidrelated properties, include decreasing levels of high-sensitivity C-reactive protein
(hsCRP), improving endothelial function, reducing inflammation at the site of the
atherosclerotic plaque, inhibiting platelet aggregation, anticoagulant, etc. .
臨床応用
The primary uses of lovastatin are the treatment of dyslipidemia and the prevention
of cardiovascular disease. It is recommended to be used only when other approaches
such as diet, exercise, and weight reduction have not improved the cholesterol profile (“Lovastatin”. The American Society of Health-System Pharmacists. Retrieved
3 April 2011.). Lovastatin is useful in treating hypercholesterolemia and combined
hyperlipidemia. However, lovastatin is not effective in treatment of receptornegative homozygous familial hypercholesterolemia .
副作用
Lovastatin's common side effects are listed in approximately descending order of occurrence frequency: creatine phosphokinase elevation, flatulence, abdominal pain, constipation, diarrhea, muscle aches or pains,
nausea, indigestion, weakness, blurred vision, rash, dizziness, and muscle cramps.
As with all statin drugs, it can rarely cause myopathy, hepatotoxicity (liver damage),
dermatomyositis, or rhabdomyolysis.
ロバスタチン 上流と下流の製品情報
原材料
準備製品