| Indication |
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. |
| Pharmacodynamics |
Etoposide is an antineoplastic agent and an epipodophyllotoxin
(a semisynthetic derivative of the podophyllotoxins). It inhibits DNA
topoisomerase II, thereby ultimately inhibiting DNA synthesis. Etoposide
is cell cycle dependent and phase specific, affecting mainly the S and
G2 phases. Two different dose-dependent responses are seen. At high
concentrations (10 µg/mL or more), lysis of cells entering mitosis is
observed. At low concentrations (0.3 to 10 µg/mL), cells are inhibited
from entering prophase. It does not interfere with microtubular
assembly. The predominant macromolecular effect of etoposide appears to
be the induction of DNA strand breaks by an interaction with
DNA-topoisomerase II or the formation of free radicals. |
| Mechanism of action |
Etoposide inhibits DNA topoisomerase II, thereby inhibiting DNA
re-ligation. This causes critical errors in DNA synthesis at the
premitotic stage of cell division and can lead to apoptosis of the
cancer cell.. Etoposide is cell cycle dependent and phase specific,
affecting mainly the S and G2 phases of cell division. |
| Absorption |
Absorbed well, time to peak plasma concentration is 1-1.5 hrs. Mean bioavailability is 50%. |
| Volume of distribution |
Not Available |
| Protein binding |
97% |
| Metabolism |
Primarily hepatic (through O-demethylation via the CYP450 3A4 isoenzyme pathway) with 40% excreted unchanged in the urine. |
| 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. Only 8% or less of an intravenous dose is excreted in the urine
as radiolabeled metabolites of 14C-etoposide. |
| Half life |
4-12 hours |
| Clearance |
- 33 – 48 mL/min [IV administration]
|
| Toxicity |
Side effects include alopecia, constipation, diarrhea, nausea and vomiting and secondary malignancies (leukemia). |
