Indications
Cytarabine is primarily indicated for the treatment of certain types of leukemia, including acute non-lymphocytic leukemia, acute lymphocytic leukemia, and the blast phase of chronic myelocytic leukemia. Additionally, Cytarabine is used in combination with daunorubicin for the treatment of newly diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in both adults and pediatric patients aged one year and older.
Pharmacodynamics
Cytarabine functions as an antineoplastic anti-metabolite, effective in the treatment of various forms of leukemia such as acute myelogenous leukemia and meningeal leukemia. As an anti-metabolite, it mimics purine or pyrimidine, disrupting the incorporation of these substances into DNA during the S phase of the cell cycle, thereby halting normal cell development and division. Within the cell, Cytarabine is metabolized into cytosine arabinoside triphosphate, its active triphosphate form. This metabolite exerts its effects through multiple mechanisms, including the inhibition of alpha-DNA polymerase and hindrance of DNA repair via an effect on beta-DNA polymerase, in addition to its incorporation into DNA. The incorporation into DNA is considered the most crucial mechanism, with cytotoxicity being highly phase-specific to the cell cycle's S phase.
Absorption
Cytarabine exhibits low oral bioavailability, with less than 20% of the administered dose being absorbed from the gastrointestinal tract. This characteristic underscores the significance of alternative administration routes to achieve therapeutic efficacy.
Mechanism of Action
Cytarabine exerts its effects primarily through the induction of direct DNA damage and its integration into DNA, thereby demonstrating cytotoxic properties against a broad spectrum of proliferating mammalian cells in culture. Its activity exhibits cell phase specificity, predominantly targeting cells in the S-phase, where DNA synthesis occurs. Under specific conditions, cytarabine can also impede the transition from the G1 phase to the S-phase. While the precise mechanism of action remains partially elucidated, it is generally understood that cytarabine functions by inhibiting DNA polymerase. Additionally, there is limited but noteworthy incorporation of cytarabine into both DNA and RNA.
