Etoposide

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Etoposide
Etoposide.svg
Etoposide ball-and-stick.png
Clinical data
Pronunciation /ˌɛtˈpsd/
Trade names Etopophos, Toposar, others
AHFS/Drugs.com Monograph
MedlinePlus a684055
Pregnancy
category
  • AU: D
  • US: D (Evidence of risk)
Routes of
administration
by mouth, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability Highly variable, 25 to 75%
Protein binding 97%
Metabolism Liver (CYP3A4 involved)
Biological half-life Oral: 6 h., IV: 6-12 h., IV in children: 3 h.
Excretion Kidney and fecal
Identifiers
Synonyms VP-16; VP-16-213
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.046.812
Chemical and physical data
Formula C29H32O13
Molar mass 588.557 g/mol
3D model (Jmol)
Melting point 243.5 °C (470.3 °F)
  (verify)

Etoposide, sold under the brand name Etopophos among others, is a chemotherapy medication used for the treatments of a number of types of cancer. This includes testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. It is used by mouth or injection into a vein.[1]

Side effects are very common. They can include low blood cell counts, vomiting, loss of appetite, diarrhea, hair loss, and fever.[1] Other severe side effects include allergic reactions and low blood pressure.[1][2] Use during pregnancy will likely harm the baby. Etoposide is in the topoisomerase inhibitor family of medication. It is believed to work by damaging DNA.[1]

Etoposide was approved for medical use in the United States in 1983.[1] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[3] The wholesale cost in the developing world is about 3.24 to 5.18 USD per 100 mg vial.[4] In the United Kingdom this costs the NHS about 12.15 pounds as of 2015.[5]

Medical uses[edit]

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.[6]

Administration[edit]

It is given intravenously (IV) or orally in capsule or tablet 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[edit]

Common are:

Less common are:

When given with warfarin, it may cause bleeding.[7]

Pharmacology[edit]

Mechanism of action[edit]

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.[8] 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.[6][9]

Chemistry[edit]

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.[10] Both these compounds have been developed with the aim of creating less toxic derivatives of podophyllotoxin.[11]

The substance is a white to yellow-brown, crystalline powder. It is soluble in organic solvents.[11]

It is used in form of its salt etoposide phosphate.

History[edit]

Etoposide was first synthesized in 1966 and U.S. Food and Drug Administration approval was granted in 1983.[6]

The nickname VP-16 likely comes from a compounding of the last name of one of the chemists who performed early work on the drug (Von Wartbung) and podophyllotoxin.[12] Another scientist who was integral in the development of podophyllotoxin-based chemotherapeutics was the medical pharmacologist Hartmann F. Stähelin.

References[edit]

  1. ^ a b c d e "Etoposide". The American Society of Health-System Pharmacists. Retrieved 8 December 2016. 
  2. ^ WHO Model Formulary 2008 (PDF). World Health Organization. 2009. p. 227. ISBN 9789241547659. Retrieved 8 December 2016. 
  3. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Retrieved 8 December 2016. 
  4. ^ "Etoposide". International Drug Price Indicator Guide. Retrieved 8 December 2016. 
  5. ^ British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 593. ISBN 9780857111562. 
  6. ^ a b c Hande KR (1998). "Etoposide: four decades of development of a topoisomerase II inhibitor". Eur. J. Cancer. 34 (10): 1514–21. doi:10.1016/S0959-8049(98)00228-7. PMID 9893622. 
  7. ^ 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. 
  8. ^ Pommier Y, Leo E, Zhang H, Marchand C (2010). "DNA topoisomerases and their poisoning by anticancer and antibacterial drugs". Chem. Biol. 17 (5): 421–33. doi:10.1016/j.chembiol.2010.04.012. PMID 20534341. 
  9. ^ Gordaliza M, García PA, del Corral JM, Castro MA, Gómez-Zurita MA (2004). "Podophyllotoxin: distribution, sources, applications and new cytotoxic derivatives". Toxicon. 44 (4): 441–59. doi:10.1016/j.toxicon.2004.05.008. PMID 15302526. 
  10. ^ Mutschler, Ernst; Schäfer-Korting, Monika (2001). Arzneimittelwirkungen (in German) (8 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 894–5. ISBN 3-8047-1763-2. 
  11. ^ a b Dinnendahl, V; Fricke, U, eds. (2015). Arzneistoff-Profile (in German). 4 (28 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3. 
  12. ^ Kuhn M, Von Wartbung A (1967). "Podophyllum- Lignane: Struktur und Absolutkonfiguration von Podorhizol-β-D-glucosid ( = Lignan F). 19. Mitt. über mitosehemmende Naturstoffe [1]". Helvetica Chimica Acta. 50 (6): 1546–65. doi:10.1002/hlca.19670500614. 

External links[edit]