Cytarine Mechanism of Action

Pharmacology: Mechanism of action: Cytarabine being an antimetabolite it interferes with the synthesis of DNA. The inhibition of the conversion of cytidine to deoxycytidine is the presumed primary site of action. Cytarabine may also be incorporated into DNA and RNA as in vitro chromosome breaks have been associated with the drug and the clinical effects are limited to tissues with a high rate of cellular proliferation. Alternatively, cytarabine may have a differentiating role rather than an antimitotic effect as the mechanism of action. Cytarabine reportedly also has immunosuppressive activity. Cytarabine is cell cycle phase-specific for the S-phase, cytarabine may also block progression from the G1-phase to the S-phase.
Pharmacokinetics: Cytarabine is rapidly metabolized and is not effective orally; less than 20 percent of the orally administered dose is absorbed from the gastrointestinal tract.
Following rapid intravenous injection of cytarabine labeled with tritium, the disappearance from plasma is biphasic. There is an initial distributive phase with a half-life of about 10 minutes, followed by a second elimination phase with a half-life of about 1 to 3 hours. After the distributive phase, more than 80 percent of plasma radioactivity can be accounted for by the inactive metabolite 1-β-D-arabinofuranosyluracil (ara-U). Within 24 hours about 80 percent of the administered radioactivity can be recovered in the urine, approximately 90 percent of which is excreted as ara-U.
Relatively constant plasma levels can be achieved by continuous intravenous infusion. After subcutaneous or intramuscular administration of cytarabine labeled with tritium, peak-plasma levels of radioactivity are achieved about 20 to 60 minutes after injection and are considerably lower than those after intravenous administration.
Cerebrospinal fluid levels of cytarabine are low in comparison to plasma levels after single intravenous injection.