Teniposide

Teniposide
Clinical data
Trade names	Vumon
Other names	VM-26
AHFS/Drugs.com	Monograph
MedlinePlus	a692045
Pregnancy; category	AU: D; ;
Routes of; administration	Intravenous
ATC code	L01CB02 (WHO) ;
Legal status
Legal status	US: ℞-only ;
Pharmacokinetic data
Bioavailability	N/A
Protein binding	>99%
Metabolism	Hepatic (CYP2C19-mediated)
Elimination half-life	5 hours
Excretion	Renal and fecal
Identifiers
	show IUPAC name
CAS Number	29767-20-2 ;
PubChem CID	34698;
IUPHAR/BPS	6843;
DrugBank	DB00444 ;
ChemSpider	31930 ;
UNII	957E6438QA;
KEGG	D02698 ;
ChEBI	CHEBI:75988 ;
ChEMBL	ChEMBL1200536 ;
CompTox Dashboard (EPA)	DTXSID8023638 ;
ECHA InfoCard	100.045.286
Chemical and physical data
Formula	C32H32O13S
Molar mass	656.66 g·mol−1
3D model (JSmol)	Interactive image;
	show SMILES
	show InChI
	(what is this?)

Teniposide (trade name Vumon) is a chemotherapeutic medication^[1] used in the treatment of childhood acute lymphocytic leukemia (ALL), Hodgkin's lymphoma, certain brain tumours, and other types of cancer.^[2] It is in a class of drugs known as podophyllotoxin derivatives and slows the growth of cancer cells in the body.^[3]

Medical uses[]

Teniposide is used for the treatment of a number of cancer types in children. In the US, it is approved for the second-line therapy of acute lymphocytic leukemia (ALL) in combination with other antineoplastic drugs.^[3] In Europe, it is also approved for the treatment of Hodgkin's lymphoma, generalized malignant lymphoma, reticulocyte sarcoma, acute leukaemia, primary brain tumours (glioblastoma, ependymoma, astrocytoma), bladder cancer, neuroblastoma and other solid tumours in children.^[2]

Administration[]

The medication is injected though a vein and burns if it leaks under the skin. It can be used in combination with other anticancer drugs.^[2]

Contraindications[]

The drug is contraindicated during pregnancy and lactation, in patients with severe liver or kidney impairment or severely impaired haematopoiesis.^[2]

Side effects[]

Teniposide, when used with other chemotherapeutic agents for the treatment of ALL, results in severe bone marrow suppression. Other common side effects include gastrointestinal toxicity, hypersensitivity reactions, and reversible alopecia.^[2]

Interactions[]

No systematic interaction studies are available. The enzyme inducers phenobarbital and phenytoin have been found to lower its blood plasma concentrations.^[4] Theoretically possible interactions include increased plasma concentrations when combined with sodium salicylate, sulfamethizole or tolbutamide, which displace teniposide from plasma protein binding, at least in vitro.^[2]^[3]

Pharmacology[]

Mechanism of action[]

Teniposide causes dose-dependent single- and double-stranded breaks in DNA and DNA-protein cross-links.^[2] The substance has been found to act as an inhibitor of topoisomerase II (an enzyme that aids in DNA unwinding),^[4]^[5] since it does not intercalate into DNA or bind strongly to DNA. The cytotoxic effects of teniposide are related to the relative number of double-stranded DNA breaks produced in cells, which are a reflection of the stabilization of a topoisomerase II-DNA intermediate.^{[citation needed]}

Chemistry[]

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

Teniposide is a semisynthetic derivative of podophyllotoxin^[2] 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 etoposide, being distinguished only by a thienyl rest where etoposide has a methyl.^[4] Both these compounds have been developed with the aim of creating less toxic derivatives of podophyllotoxin.^[6]

References[]

^ Cragg GM, Newman DJ (August 2005). "Plants as a source of anti-cancer agents". Journal of Ethnopharmacology. 100 (1–2): 72–9. doi:10.1016/j.jep.2005.05.011. PMID 16009521.
^ Jump up to: ^a ^b ^c ^d ^e ^f ^g ^h Jasek W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. pp. 8855–6. ISBN 978-3-85200-181-4.
^ Jump up to: ^a ^b ^c Drugs.com: Teniposide Monograph.
^ Jump up to: ^a ^b ^c Mutschler E, Schäfer-Korting M (2001). Arzneimittelwirkungen (in German) (8th ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 894–5. ISBN 3-8047-1763-2.
^ de Jong S, Kooistra AJ, de Vries EG, Mulder NH, Zijlstra JG (March 1993). "Topoisomerase II as a target of VM-26 and 4'-(9-acridinylamino)methanesulfon-m-aniside in atypical multidrug resistant human small cell lung carcinoma cells". Cancer Research. 53 (5): 1064–71. PMID 8382551.
^ Dinnendahl V, Fricke U, eds. (2015). Arzneistoff-Profile (in German). 4 (28th ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.

[1] Cragg GM, Newman DJ (August 2005). "Plants as a source of anti-cancer agents". Journal of Ethnopharmacology. 100 (1–2): 72–9. doi:10.1016/j.jep.2005.05.011. PMID 16009521.

[Austria-Codex-2] Jump up to: ^a ^b ^c ^d ^e ^f ^g ^h Jasek W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. pp. 8855–6. ISBN 978-3-85200-181-4.

[Drugs.com-3] Jump up to: ^a ^b ^c Drugs.com: Teniposide Monograph.

[Mutschler-4] Jump up to: ^a ^b ^c Mutschler E, Schäfer-Korting M (2001). Arzneimittelwirkungen (in German) (8th ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 894–5. ISBN 3-8047-1763-2.

[5] Jong S, Kooistra AJ, de Vries EG, Mulder NH, Zijlstra JG (March 1993). "Topoisomerase II as a target of VM-26 and 4'-(9-acridinylamino)methanesulfon-m-aniside in atypical multidrug resistant human small cell lung carcinoma cells". Cancer Research. 53 (5): 1064–71. PMID 8382551.

[6] Dinnendahl V, Fricke U, eds. (2015). Arzneistoff-Profile (in German). 4 (28th ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.

[1]

[2]

[3]

[4]

[5]

[6]