Etoposide

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Etoposide
File:Etoposide.svg
File:Etoposide ball-and-stick.png
Systematic (IUPAC) name
4'-Demethyl-epipodophyllotoxin 9-[4,6-O-(R)-ethylidene-beta-D-glucopyranoside], 4' -(dihydrogen phosphate)
Clinical data
Trade names Etopophos
AHFS/Drugs.com monograph
MedlinePlus a684055
Pregnancy
category
  • AU: D
  • US: D (Evidence of risk)
Legal status
Routes of
administration
Oral, intravenous
Pharmacokinetic data
Bioavailability Highly variable, 25 to 75%
Protein binding 97%
Metabolism Hepatic (CYP3A4 involved)
Biological half-life Oral: 6 h., IV: 6-12 h., IV in children: 3 h.
Excretion Renal and fecal
Identifiers
CAS Number 33419-42-0 YesY
ATC code L01CB01 (WHO)
PubChem CID: 36462
IUPHAR/BPS 6815
DrugBank DB00773 YesY
ChemSpider 33510 YesY
UNII 6PLQ3CP4P3 YesY
KEGG D00125 YesY
ChEBI CHEBI:4911 YesY
ChEMBL CHEMBL44657 YesY
Synonyms VP-16; VP-16-213
Chemical data
Formula C29H32O13
Molecular mass 588.557 g/mol
Physical data
Melting point 243.5 °C (470.3 °F)
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Etoposide or VP-16 (trade name Etopophos) is a cytotoxic anticancer drug which belongs to the topoisomerase inhibitor drug class. It is used in form of its salt etoposide phosphate.

It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.[1]

Medical uses

Etoposide is used as a form of chemotherapy for cancers such as Kaposi’s sarcoma, Ewing's sarcoma, lung cancer, testicular cancer, lymphoma, nonlymphocytic leukemia, and glioblastoma multiforme. It is often given in combination with other drugs (such as bleomycin in treating testicular cancer). It is also sometimes used in a conditioning regimen prior to a bone marrow or blood stem cell transplant.[2]

Administration

It is given intravenously (IV) or orally in capsule form. If the drug is given IV, it must be done slowly over a 30- to 60-minute period because it can lower blood pressure as it is being administered. Blood pressure is checked often during infusing, with the speed of administration adjusted accordingly.

Side effects

Common are:

Less common are:

When given with warfarin, it may cause bleeding.[3]

Pharmacology

Mechanism of action

Etoposide forms a ternary complex with DNA and the topoisomerase II enzyme (which aids in DNA unwinding), prevents re-ligation of the DNA strands, and by doing so causes DNA strands to break.[4] Cancer cells rely on this enzyme more than healthy cells, since they divide more rapidly. Therefore, this causes errors in DNA synthesis and promotes apoptosis of the cancer cell.[2][5]

Physical and chemical properties

An illustration of the wild mandrake, showing part of the rhizome (at bottom)

Etoposide is a semisynthetic derivative of podophyllotoxin from the rhizome of the wild mandrake (Podophyllum peltatum). More specifically, it is a glycoside of podophyllotoxin with a D-glucose derivative. It is chemically similar to the anti-cancer drug teniposide, being distinguished only by a methyl rest where teniposide has a thienyl.[6] Both these compounds have been developed with the aim of creating less toxic derivatives of podophyllotoxin.[7]

The substance is a white to yellow-brown, crystalline powder. It is soluble in organic solvents.[7]

History

Etoposide was first synthesized in 1966 and U.S. Food and Drug Administration approval was granted in 1983.[2]

The nickname VP-16 likely comes from a compounding of the last name of the chemists who performed early work on the drug (von Wartburg and von Kuhn) and podophyllotoxin.[8] Another scientist who was integral in the development of podophyllotoxin-based chemotherapeutics was the medical pharmacologist Hartmann F. Stähelin.

References

  1. "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  2. 2.0 2.1 2.2 Lua error in Module:Citation/CS1/Identifiers at line 47: attempt to index field 'wikibase' (a nil value).
  3. Longe JL (2002). Gale Encyclopedia Of Cancer: A Guide To Cancer And Its Treatments. Detroit: Thomson Gale. pp. 397–399. ISBN 978-1-4144-0362-5.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  4. Lua error in Module:Citation/CS1/Identifiers at line 47: attempt to index field 'wikibase' (a nil value).
  5. Lua error in Module:Citation/CS1/Identifiers at line 47: attempt to index field 'wikibase' (a nil value).
  6. Mutschler, Ernst; Schäfer-Korting, Monika (2001). Arzneimittelwirkungen (in German) (8 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 894–5. ISBN 3-8047-1763-2. <templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  7. 7.0 7.1 Dinnendahl, V, Fricke, U, ed. (2015). Arzneistoff-Profile (in German). 4 (28 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3. <templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  8. Lua error in Module:Citation/CS1/Identifiers at line 47: attempt to index field 'wikibase' (a nil value).

External links