Hydroxycarbamid Chemische Eigenschaften,Einsatz,Produktion Methoden
R-S?tze Betriebsanweisung:
R46:Kann vererbbare Sch?den verursachen.
R63:Kann das Kind im Mutterleib m?glicherweise sch?digen.
R61:Kann das Kind im Mutterleib sch?digen.
R40:Verdacht auf krebserzeugende Wirkung.
S-S?tze Betriebsanweisung:
S53:Exposition vermeiden - vor Gebrauch besondere Anweisungen einholen.
S36/37:Bei der Arbeit geeignete Schutzhandschuhe und Schutzkleidung tragen.
S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn m?glich, dieses Etikett vorzeigen).
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
S22:Staub nicht einatmen.
Chemische Eigenschaften
Off-White Crystalline Solid
History
Hydroxyurea has been used to reduce the frequency of painful crises in adults with sickle cell anemia since the 1980s, and it was formally approved by the FDA for use in adults in 1998, and children in 2017.
Verwenden
An anti-neoplastic - inhibits ribonucleoside reductase and DNA replication. A potential therapy for sickle cell anemia which involves the nitrosylation of sickle cell hemoglobin. Horseradish peroxidase catalyzes nitric oxide formation from hydroxyurea in the presence of hydrogen peroxide.
Indications
Hydroxyurea (Hydrea) inhibits the enzyme ribonucleotide
reductase and thus depletes intracellular pools
of deoxyribonucleotides, resulting in a specific impairment
of DNA synthesis. The drug therefore is an Sphase
specific agent whose action results in an accumulation
of cells in the late G1- and early S-phases of the
cell cycle.
Allgemeine Beschreibung
HONH-CO-NH
2. The drug is available in a 500-mg capsulefor oral use. Hydroxyurea is often considered an antimetabolitedrug, and it is used to treat myelogenousleukemia, ovarian cancer, and essential thrombocytosis. Themechanism of action of hydroxyurea involves inhibition ofDNA biosynthesis by inhibition of the enzyme ribonucleotidereductase). Resistance can occur viaincreased expression of ribonucleotide reductase. The oralbioavailability is quite high approaching 100% and the drugis distributed to all tissues. Hydroxyurea readily enters theCNS and distributes to human breast milk. A major portionof the total dose is excreted unchanged in the urine. Thedrug has been shown to increase the toxicity of 5-FU, andhydroxyurea may increase the effectiveness of some antimetaboliteHIV drugs. The toxicity profile includes myelosuppression,leucopenia, nausea, vomiting, pruritus hyperpigmentation,headache, drowsiness, and confusion.
Air & Water Reaktionen
Water soluble.
Reaktivit?t anzeigen
An amide. Amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx).
Brandgefahr
Flash point data for Hydroxyurea are not available; however, Hydroxyurea is probably combustible.
Mechanism of action
Hydroxyurea is rapidly absorbed after oral administration,
with peak plasma levels achieved approximately
1 to 2 hours after drug administration; its elimination half-life is 2 to 3 hours. The primary route of excretion
is renal, with 30 to 40% of a dose excreted unchanged.
Clinical Use
Hydroxyurea is used for the rapid lowering of blood
granulocyte counts in patients with chronic granulocytic
leukemia. The drug also can be used as maintenance
therapy for patients with the disease who have become
resistant to busulfan. Only a small percentage of patients
with other malignancies have had even brief remissions
induced by hydroxyurea administration.
Nebenwirkungen
Hematological toxicity, with white blood cells affected
more than platelets, may occur. Megaloblastosis
of the bone marrow also may be observed. Recovery is
rapid, generally within 10 to 14 days after discontinuation
of the drug. Some skin reactions, including hyperpigmentation
and hyperkeratosis, have been reported
with chronic treatment.
Stoffwechsel
Hydroxyurea has excellent oral bioavailability (80–100%), and serum levels peak within 2 hours of consuming the capsules. If a positive response is noted within 6 weeks, toxicities generally are mild enough to permit long-term or indefinite therapy on either a daily or every-3-day basis. Leukopenia and, less commonly, thrombocytopenia and/or anemia are the most serious adverse effects. Excretion of the unchanged drug and the urea metabolite is via the kidneys. The carbon dioxide produced as a by-product of hydroxyurea metabolism is excreted in the expired air.
l?uterung methode
Recrystallise hydroxyurea from absolute EtOH (10g in 150mL). Note that the rate of solution in boiling EtOH is slow (15-30minutes). It should be stored in a cool dry place, but some decomposition could occur after several weeks. [Deghenghi Org Synth Coll Vol V 645 1973.] It is very soluble in H2O and can be crystallised from Et2O. [Kfod Acta Chem Scand 10 256 1956, Beilstein 3 IV 170.]
Hydroxycarbamid Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
