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Pharmacology: Pharmacodynamics: Mechanism of Action: Etoposide is a semisynthetic derivative of the podophyllotoxins, an epipodophyllotoxin. It inhibits DNA topoisomerase II, thereby inhibiting DNA synthesis. Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G2 phases.
Pharmacokinetics: Absorption after oral doses is variable, but on average about 50% of the dose of etoposide is absorbed. The pharmacokinetics of etoposide are subject to considerable interindividual variation. It is rapidly distributed, and concentrations in plasma fall in a biphasic manner, with a terminal half-life of 4 to 11 hours.
Etoposide is about 94% bound to plasma protein. It is metabolised by the cytochrome P450 isoenzyme CYP3A4. Etoposide is excreted in urine and faeces as unchanged drug and metabolites: about 45% of a dose is reported to be excreted in urine over 72 hours. It crosses the blood brain barrier poorly; concentrations in CSF are 1 to 10% of those in plasma. It is distributed into breast milk.
