Cytarabin

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Warnung

• Gefahrenhinweise

  H317：Kann allergische Hautreaktionen verursachen.

• Sicherheit

  P202：Vor Gebrauch alle Sicherheitshinweise lesen und verstehen.

  P261：Einatmen von Staub vermeiden.

  P272：Kontaminierte Arbeitskleidung nicht außerhalb des Arbeitsplatzes tragen.

  P280：Schutzhandschuhe/Schutzkleidung/Augenschutz tragen.

  P302+P352：BEI BERÜHRUNG MIT DER HAUT: Mit viel Wasser/... (Hersteller kann, falls zweckmäßig, ein Reinigungsmittel angeben oder, wenn Wasser eindeutig ungeeignet ist, ein alternatives Mittel empfehlen) waschen.

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

Cytarabine Chemische Eigenschaften,Einsatz,Produktion Methoden

• R-Sätze Betriebsanweisung:

  R43:Sensibilisierung durch Hautkontakt möglich.
  R63:Kann das Kind im Mutterleib möglicherweise schädigen.
  R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
  R20/21/22:Gesundheitsschädlich beim Einatmen,Verschlucken und Berührung mit der Haut.

• S-Sätze Betriebsanweisung:

  S36/37:Bei der Arbeit geeignete Schutzhandschuhe und Schutzkleidung tragen.
  S37/39:Bei der Arbeit geeignete Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
  S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
  S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.

• Beschreibung

  Cytarabine (147-94-4) is a nucleoside analog that interferes with DNA synthesis and transcription, particularly in tumor cells.1,2 Cellular enzymes convert it to its nucleotide form, Ara-CTP, which disrupts DNA and RNA synthesis when polymerases attempt to incorporate it.3,4 For the same reasons, it is also employed as an antiviral.5 It inhibits proliferation of a variety of leukemic cell lines (IC50s 16-72 nM), but is used primarily against acute myeloid leukemia (AML).6

• Chemische Eigenschaften

  A white or almost white, crystalline powder, freely soluble in water, very slightly soluble in alcohol and in methylene chloride.

• Originator

  Cytosar,Upjohn,US,1969

• Verwenden

  antineoplastic, antiviral, antimetabolite

• Verwenden

  Cytarabine USP (Cytosar)is used to treat Acute granulocytic leukemia (adults); acute lymphocytic leukemia (children); Hodgkin’s disease

• Verwenden

  Used as an antineoplastic and antiviral. A selective inhibitro of DNA synthesis. Does not inhibit RNA synthesis

• Definition

  ChEBI: A pyrimidine nucleoside in which cytosine is attached to D-arabinofuranose via a beta-N1-glycosidic bond.

• Indications

  Cytarabine (cytosine arabinoside, ara-C, Cytosar-U) is an analogue of the pyrimidine nucleosides cytidine and deoxycytidine. It is one of the most active agents available for the treatment of acute myelogenous leukemia. Cytarabine kills cells in the S-phase of the cycle by competitively inhibiting DNA polymerase. The drug must first be activated by pyrimidine nucleoside kinases to the triphosphate nucleotide ara-cytosine triphosphate (ara-CTP). The susceptibility of tumor cells to cytarabine is thought to be a reflection of their ability to activate the drug more rapidly (by kinases) than to inactivate it (by deaminases).

• Manufacturing Process

  (A) Preparation of 1- (2,3,5-Tri-O-Acetyl-β-D-Arabinofuranosyl)-4-Thiouracil: A mixture of 1.85 g (5.0 mmol) of 1-(2,3,5-tri-O-acetyl-β-arabinofuranosyl) uracil, 1.23 g (5.55 mmol) of phosphorus pentasulfide, and 30 ml of pyridine was heated under gentle reflux for 2.5 hours with exclusion of moisture. The reaction mixture was cooled, and the supernatant solution was transferred by means of a pipette into a mixture of crushed ice and water. The reaction flask was washed twice with pyridine, and these washings were added to the icewater mixture. This mixture was kept at about 25°C until the ice had melted, and was then stored at 0°C for one hour. A pale yellow precipitate that formed was collected on a filter, washed with ice-water, and dried in air.
  This material was triturated with chloroform, and the chloroform mixture was filtered. A small amount of undissolved material collected on the filter and it was washed with chloroform. The chloroform solution (filtrate plus washings) was washed three times with ice-water, twice with ice-cold 3 N sulfuric acid, twice with ice-cold saturated aqueous sodium bicarbonate solution, twice with ice-water, and then dried over anhydrous sodium sulfate. The chloroform was removed under reduced pressure at a bath temperature of about 40°C, leaving a yellow, somewhat gummy residue. This yellow residue was dissolved in absolute methanol which was then evaporated at reduced pressure at about 40°C, and the residue was then held for 2 hours at 0.5 to 2.0 mm pressure and a bath temperature of about 50°C. There was thus obtained 1.69 g of 1- (2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)-4-thiouracil.
  (B) Preparation of 1-β-D-Arabinofuranosylcytosine: In a glass liner, a mixture of 1.16 g (3.0 mmol) of 1-(2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)-4- thiouracil prepared in (A) and about 60 ml of absolute methanol which had been saturated with anhydrous ammonia at 0°C was heated in a steel bomb at 98° to 105°C for 35 hours. After cooling to about 25°C and venting the bomb, the dark solution was filtered into a round-bottom flask. The methanol and excess ammonia were then removed under reduced pressure at about 25°C. The residual syrup was dissolved in absolute methanol, and the methanol was removed under reduced pressure at a bath temperature of about 40°C. This procedure of dissolving in absolute methanol and removing the solvent was repeated, and the residue was held under reduced pressure at a bath temperature of 45°C for 12 hours.
  The resulting semisolid was triturated thoroughly with absolute methanol, and the resulting suspension was chilled at 0°C. A pale tan solid that separated was collected on a filter and washed repeatedly with methanol. After washing with anhydrous ether, there was obtained 430 mg of 1-β-Darabinofuranosylcytosine.
  (C) Preparation of 1-β-D-Arabinofuranosylcytosine Hydrochloride: The absolute methanolic filtrate obtained after triturating and filtering the 1-β-Darabinofuranosylcytosine in (B) above was warmed and stirred with decolorizing charcoal. The mixture was filtered through a bed of filter aid, and the filter bed was washed repeatedly with absolute methanol. The combined filtrate and washings were pale yellow. The solution was diluted to faint cloudiness with anhydrous ether, and an excess of anhydrous hydrogen chloride was introduced. Crystallization began at about 25°C and further crystallization was induced by chilling at 0°C for 14 hours. The crystalline product was collected on a filter, washed with anhydrous ether, and dried in air. There was thus obtained 180 mg of pale yellow 1-β-Darabinofuranosylcytosine hydrochloride melting at 186° to 189°C.
  The pale yellow product was dissolved in warm, absolute methanol, and the solution after mixing with decolorizing charcoal was filtered through a bed of filter aid. The filter bed was washed with warm absolute methanol, and the combined methanolic filtrate and washings were warmed and diluted with anhydrous

• Trademarks

  Cytosar-U (Sicor); Depocyt (Skyepharma).

• Therapeutic Function

  Cancer chemotherapy

• Allgemeine Beschreibung

  Colorless crystals. Used as an antiviral agent.

• Allgemeine Beschreibung

  The drug is available in 100-, 500-, 1,000-, and 2,000-mgmultidose vials for IV use. Cytarabine is used in the treatmentof acute myelogenous leukemia and CML. This drugis a deoxycytidine analog originally isolated from thesponge Cryptothethya crypta. It is active following intracellularactivation to the nucleotide metabolite ara-CTP. Theresulting ara-CTP is incorporated into DNA resulting inchain termination and inhibition of DNA synthesis andfunction. Resistance can occur because of decreased activationor transport and increased catabolic breakdown.Metabolic breakdown within the GI tract leads to poorbioavailability. The drug distributes rapidly into tissues andtotal body water with cerebrospinal fluid (CSF) levelsreaching 20% to 40% of those in plasma. Cytidine deaminaseis the primary catabolic enzyme involved in the inactivationof cytarabine. Drug interactions include antagonismof the effects of gentamicin, decreasing the oral bioavailabilityof digoxin, as well as enhancing the cytotoxicity ofvarious alkylating agents, cisplatin, and ionizing radiation.
  Toxicities include myelosuppression, leukopenia andthrombocytopenia, nausea and vomiting anorexia, diarrhea,and mucositis. Neurotoxicity is usually expressed as ataxia,lethargy, and confusion. An allergic reaction often describedin pediatric patients includes fever, myalgia, malaise, bonepain, skin rash, conjunctivitis, and chest pain.Pretreatment with methotrexate enhances the formation ofara-CTP metabolites resulting in enhanced cytotoxicity.

• Allgemeine Beschreibung

  Cytarabine is a pyrimidine nucleoside drug that is related toidoxuridine. This agent is primarily used as an anticanceragent for Burkitt lymphoma and myeloid and lymphaticleukemias. Cytarabine blocks the cellular utilization of deoxycytidine,hence inhibiting the replication of viral DNA.Before it becomes active, the drug is converted to monophosphates,diphosphates, and triphosphates, which block DNApolymerase and the C-2 reductase that converts cytidinediphosphate into the deoxy derivative.
  The antiviral use of cytarabine is in the treatment of herpeszoster (shingles), herpetic keratitis, and viral infectionsthat resist idoxuridine. Cytarabine is usually administeredtopically. Toxicity occurs on bone marrow, the gastrointestinal(GI) tract, and the kidneys.

• Air & Water Reaktionen

  Water soluble.

• Health Hazard

  ACUTE/CHRONIC HAZARDS: Very toxic. Hazardous decomposition products. May cause irritation on contact. Teratogen. Mutagen. Central nervous system effects.

• Biochem/physiol Actions

  Ara-C incorporates into DNA and inhibits DNA replication by forming cleavage complexes with topoisomerase I resulting in DNA fragmentation; does not inhibit RNA synthesis. Anti-leukemia agent.

• Mechanism of action

  Cytarabine is rapidly metabolized in the liver, kidney, intestinal mucosa, and red blood cells and has a half-life in plasma of only 10 minutes after intravenous bolus injection. The major metabolite, uracil arabinoside (ara-U), can be detected in the blood shortly after cytarabine administration. About 80% of a given dose is excreted in the urine within 24 hours, with less than 10% appearing as cytarabine; the remainder is ara-U.When the drug is given by continuous infusion, cytarabine levels in CSF approach 40% of those in plasma.

• Clinical Use

  Cytarabine is used in the chemotherapy of acute myelogenous leukemia, usually in combination with an anthracycline agent, thioguanine, or both. It is less useful in acute lymphoblastic leukemia and the lymphomas and has no known activity against other tumors. It has been used intrathecally in the treatment of meningeal leukemias and lymphomas as an alternative to methotrexate.

• Sicherheitsprofil

  Moderate to low toxicity byingestion. Human systemic effects: allergic dermatitis,ataxia, blood changes, central nervous system effectsconjunctive irritation, degenerative brain changes, hearingacuity change, lachrymation, peripheral nervefasciculati

• Synthese

  Cytarabine, 4-amino-1-|?-arabinofuranosyl-2(1H)pyrimidone (30.1.3.8), is made from 1-|?-D-arabinofuranosyluracil by preliminary acylation of the hydroxyl group, forming a triacetyl derivative (30.1.3.6), and subsequent replacement of the carbonyl group at position 4 of the pyrimidine ring with a thiocarbonyl group using phosphorous pentachloride, and finally replacing the mercapto group of 30.1.3.7 with an amino group using ammonia and simultaneous hydrolysis of the acetyl-substituted groups, giving cytarabine (30.1.3.8).

  

• Veterinary Drugs and Treatments

  In veterinary medicine, cytarabine is used primarily in small animals as an antineoplastic agent for lymphoreticular neoplasms, myeloproliferative disease (leukemias), and CNS lymphoma. Refer to the Dosages below or the Protocols (in the appendix), for more information.

• Arzneimittelwechselwirkung

  Potentially hazardous interactions with other drugs
  Antipsychotics: avoid with clozapine, increased risk of agranulocytosis.

• Stoffwechsel

  Cytarabine is converted by phosphorylation to an active form, which is rapidly deaminated, mainly in the liver and the kidneys, by cytidine deaminase to inactive 1-β-darabinofuranosyluracil (uracil arabinoside, ara-U). Approximately 80% of an intravenous dose is excreted in the urine within 24 hours, mostly as the inactive metabolite with about 10% as unchanged cytarabine. A small amount is excreted in the bile.

• Lager

  Store at +4°C

• läuterung methode

  Purify cytarabin by recrystallisation from aqueous EtOH or a large volume of H2O (it solubility at ~20o is 5%). It has max 212 and 279nm at pH 2 and 272nm at pH 12. It is an acute leukaemic agent. [Walwick et al. Proc Chem Soc (London) 84 1959, Beilstein 25 III/IV 3669.]

• Einzelnachweise

  Derissen and Beijnen (2020), Intracellular Pharmacokinetics of Pyrimidine Analogues used in Oncology and the Correlation with Drug Action; Clin. Pharmacokinet., 59 1521 Z Li et al. (2017), Exploring the Antitumor Mechanism of High-Dose Cytarabine through the Metabolic Perturbations of Ribonucleotide and Deoxyribonucleotide in Human Promyelocytic Leukemia HL-60 Cells; Molecules, 22 E499 Zhang & Kiechle (2004), Cytosine Arabinoside Substitution Decreases Transcription Factor-DNA Binding Element Complex Formation; Arch. Pathol. Lab. Med., 128 1364 Renis (1973), Antiviral Activity of Cytarabine in Herpesvirus–Infected Rats; Antimicrob. Agents Chemother., 4 439 Qin et al. (2007), Effect of Cytarabine and Decitabine in Combination in Human Leukemic Cell Lines; Clin. Cancer Res., 13 4225 Walter et al. (2020), Optimal Dosing of Cytarabine in Induction and Post-Remission Therapy of Acute Myeloid Leukemia; Leukemia, 35 295

Cytarabine Upstream-Materialien And Downstream Produkte

Cytarabin Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global(703)Suppliers

147-94-4, Cytarabine Verwandte Suche: