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| Pronunciation | /ˌɛtoʊˈpoʊsaɪd/ |
| Trade names | Etopophos, Toposar, Vepesid, others |
| Other names | VP-16; VP-16-213 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a684055 |
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| Routes of administration | By mouth,intravenous |
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| Pharmacokinetic data | |
| Bioavailability | Highly variable, 25 to 75% |
| Protein binding | 97% |
| Metabolism | Liver (CYP3A4 involved) |
| Eliminationhalf-life | Oral: 6 h., IV: 6-12 h., IV in children: 3 h. |
| Excretion | Kidney and fecal |
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| ECHA InfoCard | 100.046.812 |
| Chemical and physical data | |
| Formula | C29H32O13 |
| Molar mass | 588.562 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 243.5 °C (470.3 °F) |
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Etoposide, sold under the brand nameVepesid among others, is achemotherapy medication used for the treatments of a number of types ofcancer includingtesticular cancer,lung cancer,lymphoma,leukemia,neuroblastoma, andovarian cancer.[1] It is also used forhemophagocytic lymphohistiocytosis.[2] It is used by mouth orinjection into a vein.[1]
Side effects are very common.[1] They can includelow blood cell counts, vomiting, loss of appetite, diarrhea, hair loss, and fever.[1] Other severe side effects includeallergic reactions andlow blood pressure.[1][3] Use duringpregnancy will likely harm the fetus.[1] Etoposide is in thetopoisomerase inhibitor family of medication.[1] 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 theWorld Health Organization's List of Essential Medicines.[4]
Etoposide is used as a form ofchemotherapy for cancers such asKaposi's sarcoma,Ewing's sarcoma,lung cancer,testicular cancer,lymphoma, nonlymphocyticleukemia, andglioblastoma multiforme. It is often given in combination with other drugs (such asbleomycin in treating testicular cancer). It is also sometimes used in a conditioning regimen prior to abone marrow orblood stem cell transplant.[5]
It is givenintravenously (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 lowerblood pressure as it is being administered.[1] Blood pressure is checked often during infusing, with the speed of administration adjusted accordingly.[citation needed]
Common are:[citation needed]
Less common are:[citation needed]
When given withwarfarin, it may cause bleeding.[6]
Etoposide forms a ternary complex withDNA and thetopoisomerase II enzyme, which is an enzyme that aids in relaxing negative or positivesupercoils in DNA. Topoisomerase II normally will form a double-stranded break in one DNA double-strand, allow another to pass through, andre-ligate the broken strands. Etoposide's binding prevents topoisomerase II fromre-ligating the broken DNA strands, which causes the DNA breaks made by topoisomerase II to stay broken, and also prevents the topoisomerase II molecule from leaving the site and relieving tension elsewhere. This results in a double-strand break in the DNA that can have various deleterious effects on the cell, and depletion of topoisomerase II available to relieve further tension.[7]Cancer cells rely on this enzyme more than healthy cells, since they divide more rapidly. Therefore, this causes errors inDNA synthesis and promotesapoptosis of the cancer cell.[5][8]
Etoposide is asemisynthetic derivative ofpodophyllotoxin from therhizome of themayapple (or "American mandrake",Podophyllum peltatum). More specifically, it is aglycoside of podophyllotoxin with aD-glucose derivative. It is chemically similar to the anti-cancer drugteniposide, being distinguished only by amethyl group where teniposide has athienyl.[9] Both these compounds have been developed with the aim of creating less toxic derivatives of podophyllotoxin.[10]
The substance is a white to yellow-brown, crystalline powder. It is soluble in organic solvents.[10]
It is used in form of itssalt etoposide phosphate.[citation needed]
Etoposide was first synthesized in 1966 and U.S.Food and Drug Administration approval was granted in 1983.[5]
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 Wartburg) and podophyllotoxin.[11] Another scientist who was integral in the development of podophyllotoxin-based chemotherapeutics was the medical pharmacologistHartmann F. Stähelin.[citation needed]
