Axibin Mechanism of Action

Pharmacology: Pharmacodynamics: Doxorubicin is an antitumour agent. Tumour cells are probably killed through drug-induced alterations of nucleic acid synthesis although the exact mechanism of action has not yet been clearly elucidated.
Proposed mechanism of action include: DNA intercalation (leading to an inhibition of synthesis of DNA, RNA and proteins), formation of highly reactive free-radicals and superoxides, chelation of divalent cations, the inhibition of Na-K ATPase and the binding of doxorubicin to certain constituents of cell membranes (particularly to the membrane lipids, spectrin and cardiolipin). Highest drug concentrations are attained in the lung, liver, spleen, kidney, heart, small intestine and bone-marrow. Doxorubicin does not cross the blood-brain barrier.
Pharmacokinetics: After IV administration, the plasma disappearance curve of doxorubicin is triphasic with half-lives of 12 minutes, 3.3 hours and 30 hours. The relatively long terminal elimination half-life reflects doxorubicin's distribution into a deep tissue compartment. Only about 33 to 50% of fluorescent or tritiated drug (or degradation products), respectively, can be accounted for in urine, bile and faeces for up to 5 days after IV administration. The remainder of the doxorubicin and degradation products appear to be retained for long periods of time in body tissues.
In cancer patients, doxorubicin is reduced to adriamycinol, which is an active cytotoxic agent. This reduction appears to be catalysed by cytoplasmic and pH-dependent aldo-keto reductases that are found in all tissues and play an important role in determining the overall pharmacokinetics of doxorubicin.
Microsomal glycosidases present in most tissues split doxorubicin and adriamycinol into inactive aglycones. The aglycones may then undergo 0-demethylation, followed by conjugation to sulphate or glucuronide esters, and excretion in the bile.