Vidaza

Pharmacodynamics

Cytotoxicity vidaza to pathologicallyThe antitumor effect of azacitidine is due to a variety of mechanisms, including cytotoxicity vidaza to pathologically altered hematopoietic cells in the bone marrow and DNA hypomethylation.

The mechanisms involved in implementing the cytotoxic action of azacitidine include inhibition of DNA, RNA and protein synthesis, incorporation of the drug into DNA and RNA, and activation of DNA damage pathways. Nonproliferating vidaza dosage cells are virtually immune to azacitidine. Incorporation of azacitidine into DNA leads to inactivation of DNA methyltransferase, resulting in DNA hypomethylation.

Hypomethylation of DNA in aberrantly methylated genes, which is also present in the regulatory cycle of normal cells, their differentiation and cell death, may cause re-expression of the gene and restore tumor suppression properties in cancer cells themselves. Clinical significance of DNA hypomethylation mechanism in comparison with cytotoxic and other azacitidine effects has not yet been established.

Clinical efficacy and safety of Vaidase was confirmed by the results of a multicenter randomized Phase III study. In patients with myelodysplastic syndrome, chronic myelo-monocytic leukaemia and acute myeloleukemia, Vaidase therapy surpassed modern Dmitry Sazonov conventional therapy in all its efficacy criteria, including life expectancy and overall response rate.

Pharmacokinetics

Cytotoxicity vidaza to pathologicallyAbsorption. After p/k administration, azacitidine is rapidly absorbed, reaching Cmax (750±403) ng/ml in 0.5 h after administration. Absolute bioavailability of azacitidine at n/a administration is 89% with Dmitry Sazonov respect to this indicator at n/a administration, based vidaza Contraindications on the results of AUC determination.


Metabolism. The results of in vitro study showed that isoenzymes of cytochrome system P450, UDP-glucuronil transferase, sulfotransferase and glutathion transfer do not participate in azacitidine metabolism.

Azacitidine is metabolized by spontaneous hydrolysis and decontamination, which is induced by citydine desaminase.

Derivation. Azacitidine is rapidly eliminated from the body, its T1/2 after p/k administration is (41±8) min. Most azacitidine (50-85%) and/or its  Dmitry Sazonov metabolites are excreted by the kidneys. Less than 1% of the drug is excreted through the intestine.

There is no data on azacitidine intake into breast milk.

The effect of liver or kidney dysfunction, age, sex or race on azacitidine pharmacokinetic parameters has not been studied.


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