Gemfibrozil

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Warnung

• Gefahrenhinweise

  H302：Gesundheitsschädlich bei Verschlucken.

Gemfibrozil Chemische Eigenschaften,Einsatz,Produktion Methoden

• R-Sätze Betriebsanweisung:

  R22:Gesundheitsschädlich beim Verschlucken.
  R63:Kann das Kind im Mutterleib möglicherweise schädigen.
  R62:Kann möglicherweise die Fortpflanzungsfähigkeit beeinträchtigen.
  R46:Kann vererbbare Schäden verursachen.
  R36/38:Reizt die Augen und die Haut.
  R21:Gesundheitsschädlich bei Berührung mit der Haut.

• S-Sätze Betriebsanweisung:

  S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
  S53:Exposition vermeiden - vor Gebrauch besondere Anweisungen einholen.
  S36/37:Bei der Arbeit geeignete Schutzhandschuhe und Schutzkleidung tragen.
  S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
  S25:Berührung mit den Augen vermeiden.

• Beschreibung

  Gemfibrozil is a peroxisome proliferator-activated receptor α (PPARα) and PPARγ agonist (EC₅₀s = 193.3 and 147.8 μM, respectively, in transactivation assays). In vivo, gemfibrozil (50 mg/kg, p.o.) reduces serum total cholesterol, triglyceride, and LDL levels in a rat model of high-cholesterol diet-induced hyperlipidemia. Gemfibrozil (100 mg/kg per day) reduces atherosclerotic plaque area, superoxide production, and expression of the genes encoding the NF-κB subunit p65 and chemokine (C-C) motif ligand 2 (CCL2) in ApoE^-/- mice. Formulations containing gemfibrozil have been used in the treatment of high cholesterol.

• Chemische Eigenschaften

  White Crystalline Powder

• Originator

  Lopid,Warner Lambert,US,1982

• Verwenden

  This drug is used for hyperlipoproteinemia that cannot be corrected by a special diet or by physical exertion.

• Verwenden

  A serum lipid regulating agent used as an antihyperlipoproteinemic

• Verwenden

  Gemfibrozil has been used to to study its effects on cell cycle progression in yeast. It has been used to study the effects of fibrates on cell proliferation and gene expression in human cell lines.

• Definition

  ChEBI: Gemfibrozil is an aromatic ether. It has a role as an antilipemic drug. It is functionally related to a valeric acid.

• Manufacturing Process

  With stirring, 44.1 g of isobutyric acid is added to a mixture of 51.0 g of diisopropylamine, 23.2 g of a 57% sodium hydride dispersion in mineral oil, and 350 ml of tetrahydrofuran. When gas evolution subsides, the mixture is heated at reflux for 15 minutes, cooled to 0°C, and treated with 345 ml of a 1.45M solution of n-butyl lithium in heptane. After 5 hr, the mixture is warmed one-half hour at 30°C, cooled to 0°C, and treated with 122.0 g of 3- (2,5-xylyloxy)propyl bromide. After one more hour, it is stirred with 500 ml of water and the aqueous phase is separated and acidified with 150 ml of 6N hydrochloric acid. The acidic mixture is extracted with ether and the ether extract is washed with saturated sodium chloride solution, dried over magnesium sulfate, concentrated almost to dryness, and distilled in vacuo. A distillate of 2,2-dimethyl-5-(2,5-xylyloxy)valeric acid is collected at boiling point 158°C to 159°C at 0.02 mm of Hg; melting point 61°C to 63°C following crystallization from hexane.
  The same product is obtained by substituting 4.4 g of lithium hydride for the sodium hydride in the above procedure.
  The same product is also obtained in the following manner. A mixture of 26.4 g of isobutyric acid, 6.0 g of magnesium oxide powder, and 250 ml of toluene is stirred and heated at reflux with continuous removal of the water formed in the reaction. When water formation ceases, the resulting mixture containing magnesium isobutyrate is concentrated to one-half its original volume, cooled in an ice bath, and treated with 31.0 g of diisopropylamine in 200 mi of dry tetrahydrofuran and then with 179 ml of 1.68M n-butyl lithium in heptane while the temperature is maintained below 10°C. After 15 more minutes, the mixture is warmed at 30°C for one-half hour, cooled to 0°C to 10°C, and treated with 75.0 g of 3-(2,5-xylyloxy)propyl bromide. The mixture is then stirred for 18 hr at room temperature and diluted with 125 ml of 6N hydrochloric acid and 250 ml of water. The organic phase is separated, concentrated, and the residue distilled in vacuo to give 2,2-dimethyl-5-(2,5- xylyloxy)valeric acid.

• Trademarks

  Lopid (Pfizer);Gevilon;Hipolixan;Ipolipid;Lipur;Tenorac.

• Therapeutic Function

  Antihyperlipidemic

• Weltgesundheitsorganisation (WHO)

  Gemfibrozil, an antihyperlipidaemic derivative of clofibrate, was introduced in the early 1980's. It is registered in several countries for the treatment of hyperlipidaemia unresponsive to dietary measures. (See also the WHO comment for clofibrate).

• Allgemeine Beschreibung

  Gemfibrozil, 5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid (Lopid), is a congener of clofibratethat was used first in the treatment of hyperlipoproteinemia inthe mid-1970s. Its mechanism of action and use are similar tothose of clofibrate. Gemfibrozil reduces plasma levels ofVLDL triglycerides and stimulates clearance of VLDL fromplasma. The drug has little effect on cholesterol plasma levelsbut does cause an increase of HDL.
  Gemfibrozil is absorbed quickly from the gut and excretedunchanged in the urine. The drug has a plasma half-life of1.5 hours, but reduction of plasma VLDL concentration takesbetween 2 and 5 days to become evident. The peak effect of its hypolipidemic action may take up to 4 weeks to becomemanifest.

• Biochem/physiol Actions

  Gemfibrozil selectively increases Apolipoprotein A-I levels. In yeast cells, application of gemfibrozil delays the start of DNA replication. It is used as a therapeutic agent for dyslipidemia.

• Mechanism of action

  From the chemical point of view, gemfibrozil is somewhat related to clofibrate and has analogous pharmacological use. The primary action of gemibrozil as well as clofibrate consists of a significant reduction in the level of very low-density proteins in the plasma and an increase in high-density protein formation.

• Clinical Use

  Hyperlipidaemias of types IIa, IIb, III, IV and V

• Synthese

  Gemfibrozil, 2,2-dimethyl-5-(2,5-dimethylphenoxy)valeric acid (20.2.4), is synthesized either by hydrolysis of ethyl ester of 2,2-dimethyl-5-(2,5-dimethylphenoxy) valeric acid (20.2.3), which is synthesized by alkylation 2,2-dimethylvaleric acid ethyl ester with 3-(2,5-dimethylphenoxy)propylbromide-1 in the presence of lithium diisopropylamide, or by oxidation of the corresponding aldehyde (20.2.4).

  

• Veterinary Drugs and Treatments

  Gemfibrozil may be useful to reduce serum triglycerides in those dogs or cats with hypertriglyceridemia and when diet modifications alone have been unsuccessful. One reference (Elliott 2005) suggests not adding drug therapy to treat hypertriglyceridemia unless the serum triglyceride concentration exceeds 500 mg/dL with associated clinical signs.

• Arzneimittelwechselwirkung

  Potentially hazardous interactions with other drugs
  Antibacterials: increased risk of myopathy with daptomycin - try to avoid concomitant use.
  Anticoagulants: enhances effect of coumarins and phenindione; dose of anticoagulant should be reduced by up to 50% and adjusted by monitoring INR.
  Antidiabetics: may improve glucose tolerance and have an additive effect with insulin or sulphonylureas; possibly enhanced effect with nateglinide; increased risk of severe hypoglycaemia with repaglinide - avoid.
  Antivirals concentration of paritaprevir increased - avoid.
  Ciclosporin: Parke-Davis have one report on file of an interaction with ciclosporin where serum ciclosporin levels were decreased. No effects on muscle were noted.
  Colchicine: possible increased risk of myopathy.
  Cytotoxics: bexarotene concentration increased - avoid; concentration of enzalutamide increased - avoid or halve enzalutamide dose.
  Lipid-regulating drugs: increased risk of myopathy in combination with statins and ezetimibe - avoid (maximum 20 mg of rosuvastatin).

• Stoffwechsel

  Gemfibrozil undergoes oxidation of a ring methyl group to form successively a hydroxymethyl and a carboxyl metabolite (the main metabolite). This metabolite has a low activity compared to the mother compound gemfibrozil and an elimination half-life of approximately 20 hours.
  Gemfibrozil is eliminated mainly by metabolism. Approximately 70% of the administered human dose is excreted in the urine, mainly as conjugates of gemfibrozil and its metabolites. Less than 6% of the dose is excreted unchanged in the urine; 6% of the dose is found in faeces.

Gemfibrozil Upstream-Materialien And Downstream Produkte

Gemfibrozil Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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