Cytarabine is a cytostatic drug and is used primarily to treat acute myeloid leukemia. In this indication, it is among the most commonly used cytostatic drugs. It is also used in acute lymphoblastic leukemia (also known as acute lymphocytic leukemia), myelodysplastic syndrome and non-Hodgkin’s lymphoma. Cytarabine also has a virostatic effect, although it is not used as a virostatic agent.
What is cytarabine?
Cytarabine is an isomer of the nucleoside cytidine belonging to the arabinosyl nucleoside group. Instead of the β-D-ribofuranose common in nucleosides, it has a β-D-arabinofuranose. Cytarabine is composed of a furanose (sugar) and the cytosine. The chemical molecular formula of the substance is C9H13N3O5. Cytarabine has a molar mass of 243.17 g x mol^-1 and exists as a colorless solid. Cytarabine is readily soluble in water. The melting point is 212-213 degrees Celsisu. Cytarabine is a cytostatic and is classified as an antimetabolite based on its mechanism of action. The lethal dose 50 in rats is >5 mg x kg^-1 when administered intravenously and >500 mg x kg^-1 when administered orally. Furthermore, cytarabine also has virostatic activity, but it is rarely used as a virostatic agent.
Pharmacologic Action
Cytarabine is used as a cytostatic agent. The substance acts as an antimetabolite, meaning that cytarabine resembles a natural metabolite and inhibits its metabolic pathway. Through this mechanism, cytarabine interferes with a normal process (in this case, DNA replication). This is the cause of the cytostatic effect. Cytotoxicity is then exploited medically to treat cancer. To clarify the mechanism of action of cytarabine, it must first be said that cytarabine is phosphorylated in the body to cytosine arinoside triphosphate. Cytosinarabinoside triphosphate is the actual active substance. This substance is incorporated into DNA during DNA replication instead of the nucleotide cytidine triphosphate. The active form of cytarabin thus replaces the DNA building block cytidine triposphate. This is possible because cytarabine is chemically similar to cytidine triposphate. Furthermore, cytarabine blocks DNA repair mechanisms. Overall, cytarabine has a cytotoxic, or cell-damaging, effect via the processes described. The cytotoxic effect is almost exclusively during the S phase of the cell cycle. Regarding the pharmacokinetics of cytarabine, it should be noted that cytarabine is liquid-permeable when administered intravenously and subcutaneously. After oral administration, less than 20% of the administered cytarabine is absorbed into the bloodstream. Cytarabine can also be administered intrathecally (into the subarachnoid space). In high doses, it is able to cross the blood–brain barrier and thus can exert an effect in the brain. Plasma protein binding of the substance is 13%. Metabolization takes place in the liver. Cytarabine is metabolized to the two metabolites cytosine arabinoside triphosphate and uracil arabinoside, the former being active but the latter not. Elimination occurs via cytosine deaminases in the liver and kidney.
Medical application and use
Medically, cytarabine is used as a cytostatic agent. The main application of the drug is acute myeloid leukemia (AML). Cytarabine is one of the most important cytostatic drugs and is administered in almost every AML treatment. In addition, the substance is used in acute lymphoblastic leukemia. A frequently used regimen is the so-called 7+3 regimen, in which cytarabine is administered for seven days followed by a substance from the anthracycline group for three days. The indications of cytarabine in children and adolescents as well as in adults are acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS) and non-Hodgkin’s lymphoma (NHL). The dosage of the cytostatic drug depends on the disease being treated and the patient’s age, height, and body weight.
Risks and side effects
The cytotoxic effect of cytarabine affects not only the degenerated cancer cells but also healthy cells of the organism. This can lead to sometimes severe side effects. However, it should be noted here that these side effects must be accepted in many cases in order to save the patient’s life. If left untreated, the diseases for which cytarabine is indicated are fatal.Side effects include:
Hair loss (alopecia), nausea, bone marrow depression (damage to the bone marrow that results in decreased formation of blood cells), vomiting (emesis), anemia (in anemia, there is a decreased level of hemoglobin and an insufficient number of erythrocytes in the blood. As a result, not enough oxygen can be transported). In addition, thrombocytopenia (a decreased number of platelets, called thrombocytes, in the blood), neutropenia (neutropenia is a decrease in neutrophil granulocytes, a subtype of leukocytes, in the blood), meningitis (meningitis), dyspnea (shortness of breath), mucositis (inflammation of the mucous membranes), and liver damage are regular side effects.
