Definition
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
Description
A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Primarily hepatic (through O-demethylation via the CYP450 3A4 isoenzyme pathway) with 40% excreted unchanged in the urine. Etoposide also undergoes glutathione and glucuronide conjugation which are catalyzed by GSTT1/GSTP1 and UGT1A1, respectively. Prostaglandin synthases are also responsible for the conversion of etoposide to O-demethylated metabolites (quinone). Route of Elimination: Etoposide is cleared by both renal and nonrenal processes, i.e., metabolism and biliary excretion. Glucuronide and/or sulfate conjugates of etoposide are also excreted in human urine. Biliary excretion of unchanged drug and/or metabolites is an important route of etoposide elimination as fecal recovery of radioactivity is 44% of the intravenous dose. 56% of the dose was in the urine, 45% of which was excreted as etoposide. Half Life: 4-11 hours
- Uses/Sources: For use in combination with other chemotherapeutic agents in the treatment of refractory testicular tumors and as first line treatment in patients with small cell lung cancer. Also used to treat other malignancies such as lymphoma, non-lymphocytic leukemia, and glioblastoma multiforme.
- Symptoms: Side effects include alopecia, constipation, diarrhea, nausea and vomiting and secondary malignancies (leukemia).
- Route of Exposure: Absorbed well, time to peak plasma concentration is 1-1.5 hrs. Mean bioavailability is 50% (range of 25% - 75%). Cmax and AUC values for orally administered etoposide capsules display intra- and inter-subject variability. There is no evidence of first-pass effect for etoposide.
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
DNA topoisomerase 2-alpha DNA topoisomerase 2-beta |
17361331 16309315 16377807 16271071 17514873 17578914 11752352 |