Lovastatin

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Warnung

• Gefahrenhinweise

  H351：Kann vermutlich Krebs verursachen.

• Sicherheit

  P201：Vor Gebrauch besondere Anweisungen einholen.

  P202：Vor Gebrauch alle Sicherheitshinweise lesen und verstehen.

  P280：Schutzhandschuhe/Schutzkleidung/Augenschutz tragen.

  P308+P313：BEI Exposition oder falls betroffen: Ärztlichen Rat einholen/ärztliche Hilfe hinzuziehen.

  P405：Unter Verschluss aufbewahren.

  P501：Inhalt/Behälter ... (Entsorgungsvorschriften vom Hersteller anzugeben) zuführen.

Lovastatin Chemische Eigenschaften,Einsatz,Produktion Methoden

• R-Sätze Betriebsanweisung:

  R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.

• S-Sätze Betriebsanweisung:

  S22:Staub nicht einatmen.
  S24/25:Berührung mit den Augen und der Haut vermeiden.
  S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
  S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.

• Beschreibung

  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.

• Chemische Eigenschaften

  White Solid

• Physikalische Eigenschaften

  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.

• Originator

  Merck (USA)

• History

  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 .

• Verwenden

  An antihypercholesterolemic agent. A fungal metabolite, which is a potent inhibitor of HMG-CoA reductase

• Verwenden

  Cardiovascular

• Verwenden

  anti-hyperlipoproteinemic, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor

• Verwenden

  antiarrhythmic

• Verwenden

  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.

• Indications

  Hypercholesterolemia, combined hyperlipidemia.

• Definition

  ChEBI: Lovastatin is a fatty acid ester that is mevastatin carrying an additional methyl group on the carbobicyclic skeleton. It is used in as an anticholesteremic drug and has been found in fungal species such as Aspergillus terreus and Pleurotus ostreatus (oyster mushroom). It has a role as an Aspergillus metabolite, a prodrug, an anticholesteremic drug and an antineoplastic agent. It is a polyketide, a statin (naturally occurring), a member of hexahydronaphthalenes, a delta-lactone and a fatty acid ester. It is functionally related to a (S)-2-methylbutyric acid and a mevastatin.

• Manufacturing Process

  1) Coniothyrium fuckelii ATCC 74227 was grown in a sterilizable fermentation apparatus with a volume of 15 L. The apparatus was equipped with an agitator, aerator, pH control system, dissolved oxygen control system, and a pump and feed system designed to allow the sterile addition of glucose solutions. The pH was controlled by the automatic addition of ammonium hydroxide or phosphoric acid to maintain the pH of the culture medium constant at 5.0. Periodically, the fermentation broth was sampled, measured for glucose concentration and an addition of glucose was made manually to maintain a concentration of glucose at approximately 2-5 g/L. After 192 hours of growth under these conditions, the concentration of biomass reached 65 g/L and the concentration of Lovastatin reached 102 mg/L.
  2) A further medium for the growth of Coniothyrium fuckelii ATCC 74227, has the following composition: Glucose 12%, Peptone 1%, (NH4)2SO4 0.4%, MgSO4 · 7H2O 0.05%, P 2000 0.1% (Antifoam agent), L-isoleucine 0.2-1.5%, L-aspartic acid 0.2-1.5%. The fermentation was carried out as before.
  With this medium, the lovastatin concentration was 430 mg/L.

• Trademarks

  Altoprev (Andrx); Mevacor (Merck).

• Therapeutic Function

  Antihyperlipidemic

• Allgemeine Beschreibung

  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.

• Biologische Aktivität

  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 .

• Pharmakologie

  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. .

• Clinical Use

  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 .

• Nebenwirkungen

  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.

• Lager

  Store at RT

• Einzelnachweise

  1) Alberts et al. (1988), Discovery, biochemistry and biology of lovastatin;? Am. J. Cardiol., 62 10J 2) Hancock et al. (1989), All ras proteins are polyisoprenylated but only some are palmitoylated;? Cell, 57 1167 3) Park et al. (1999), Lovastatin-induced inhibition of HL-60 cell proliferation via cell cycle arrest and apoptosis;? Anticancer Res., 19 3133 4) Vilimanovich et al. (2015), Statin-mediated inhibition of cholesterol synthesis induces cytoprotective autophagy in human leukemic cells;? Eur. J. Pharmacol., 765 415 5) Tobert et al. (1988), Efficacy and long-term adverse effect pattern of lovastatin;? Am. J. Cardiol., 62 28J

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