Cytarabine actions

Prior to the introduction of imatinib, the combination of interferon-alfa and low dose cytarabine was the nontransplant treatment of choice for patients in chronic phase CML. The precise mechanism of action of interferon-alfa remains unknown. The addition of cytarabine to interferon-alfa improves the response compared with interferon alone. This combination produces cytogenetic response rates of 30%, much lower than imatinib.13 One of the major drawbacks, in addition to the low response rates, is interferon s toxicity,... 

Thioguanine (6-TG) also inhibits several enzymes in the de novo purine nucleotide biosynthetic pathway. Various metabolic lesions result, including inhibition of purine nucleotide interconversion decrease in intracellular levels of guanine nucleotides, which leads to inhibition of glycoprotein synthesis interference with the formation of DNA and RNA and incorporation of thiopurine nucleotides into both DNA and RNA. 6-TG has a synergistic action when used together with cytarabine in the treatment of adult acute leukemia. 

The mode of action of mitoxantronc involves intercalation and inhibition of topoisomcrasc 11. In contrast to doxorubicin. it docs not undergo redox cycling to form oxygen free radicals, because iLs redox potential is outside the reductive capability of mammalian reductases. Mitoxantrone is approved for remission-induction therapy in acute nonlympho-cytic leukemia, where it typically is used with cytarabine. It also is active against other leukemias, breast cancer, and ovarian cancer. The dose-limiting toxic effect is myelosup-... 

Gemcitabine is a fluorine-substituted deoxycytidine analog related structurally to cytarabine (see Table 124—11). Its activation and mechanism of action are similar to those of cytarabine. Gemcitabine is incorporated into DNA, where it inhibits DNA polymerase activity. It also inhibits ribonucleotide reductase. Compared with cytarabine. 

Cytarabine is a pyrimidine analogue, which is incorporated into both RNA and DNA and interferes with the action of DNA polymerase. Cytarabine is used to treat leukaemia. 

Mechanisms of action and resistance Cytarabine (cytosine arabinoside) is a pyrimidine antimetabolite. The drug is activated by kinases to AraCTP, an inhibitor of DNA polymerases. Of all the antimetabolites, cytarabine is the most specific for the S phase of the tumor cell cycle. Resistance to cytarabine can occur as a result of its decreased uptake or its decreased conversion to AraCTP. 

The mechanism of action of fluorouracil and cytarabine discussed under Section 2.2.3 shall now be treated individually as under ... 

The use of pharmaceuticals in form of emulsions is of special interest. Thus, for example, o/w emulsions stabilised by surfactants, such as mono- and diglycerides, are successfully used as pseuo-doxime-proxetil protection from intestinal lumen hydrolysis through oral administration [128]. Multiple w/o/w emulsions stabilised by Tween 20/Span 20 or Tween 80/Span 80 mixtures contributed to a prolonged retention of cytarabine in one of the phases, and its gradual release ensured a prolonged action of the drug [129]. 

The antiviral action of 5-iododeox5oiridine (lUdR) (4.9) has already been described in Section 4.0. It is widely prescribed for herpetic infections of the conjimctiva. Cytarabine ( Ara C ) (4./0), more selective, is used for severe generalized herpes in man (see Section 4.0). Vidarabine ( Ara A ) (4.JJ), a newer drug, has given useful clinical results in viral pneumonia and herpetic encephalitis (Section 4.0). The action of all these substances is to block stages in the synthesis of viral nucleic acids. 

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