Vincristine

verifiedfields	changed
watchedfields	changed
verifiedrevid	461759697
width	240
image2	Vincristine3DanBS.gif
width2	200
pronounce	‡R1R‡
tradename	Oncovin, others‡R2R‡
medlineplus	a682822
dailymedid	Vincristine
pregnancy au	D
routes of administration	intravenous
atc prefix	L01
atc suffix	CA02
legal au	S4
legal ca	Rx-only
legal uk	POM
legal us	Rx-only
bioavailability	n/a (not reliably absorbed by the GI tract)
protein bound	~44%‡R3R‡
metabolism	Liver, mostly via CYP3A4 and CYP3A5
elimination half-life	19 to 155 hours (mean: 85 hours)
excretion	Faeces (70–80%), urine (10–20%)‡R4R‡
iuphar ligand	6785
cas number	57-22-7
pubchem	5978
drugbank	DB00541
chemspiderid	5758
unii	5J49Q6B70F
kegg	D08679
chebi	28445
chembl	303560
synonyms	leurocristine ki
iupac name	(3aR,3a1R,4R,5S,5aR,10bR)-Methyl 4-acetoxy-3a-ethyl-9-((5S,7S,9S)-5-ethyl-5-hydroxy-9-(methoxycarbonyl)-2,4,5,6,7,8,9,10-octahydro-1H-3,7-methano[1]azacycloundecino[5,4-b]indol-9-yl)-6-formyl-5-hydroxy-8-methoxy-3a,3a1,4,5,5a,6,11,12-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate
c	46
h	56
n	4
o	10
smiles	CC[C@@]1(C[C@@H]2C[C@@](C3=C(CCN(C2)C1)C4=CC=CC=C4N3)(C5=C(C=C6C(=C5)[C@]78CCN9[C@H]7[C@@](C=CC9)([C@H]([C@@]([C@@H]8N6C=O)(C(=O)OC)O)OC(=O)C)CC)OC)C(=O)OC)O
stdinchi	1S/C46H56N4O10/c1-7-42(55)22-28-23-45(40(53)58-5,36-30(14-18-48(24-28)
stdinchikey	OGWKCGZFUXNPDA-XQKSVPLYSA-N

Vincristine, also known as leurocristine and sold under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer.[5] This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin lymphoma, neuroblastoma, and small cell lung cancer among others.[5] It is given intravenously.[5]

Most people experience some side effects from vincristine treatment.[5] Commonly it causes a change in sensation, hair loss, constipation, difficulty walking, and headaches.[5] Serious side effects may include neuropathic pain, lung damage, or low white blood cells which increases the risk of infection.[5]

Society and culture

Suppliers

Two generic drug makers were suppliers of vincristine in the United States: Teva and Pfizer. In 2019 Teva stopped producing vincristine, leaving Pfizer as the only company in production. Teva has said that they will restart production, and expect it to be available in 2020.[30]

Shortage

In October 2019 an impending shortage was reported; no adequate substitute is known for treating childhood cancers.[31] By 2022, the shortage of vincristine continued.[32]

Controversy

Pharmaceutical bioprospecting

Vincristine's origins are debated as an example of pharmaceutical bioprospecting in the fields of ethnobotany and ethnomedicine. Some consider the Catharanthus roseus plant from which vincristine is derived, and its folk remedies to be endemic to Madagascar, and that Madagascar was denied royalties from vincristine sales.[33] However, Catharanthus roseus has a documented history in folk medicine treatments in other locations. In 1963, Lilly researchers acknowledged that the plant was used in Brazil to treat hemorrhage, scurvy, toothaches, and chronic wounds; in the British West Indies to treat diabetic ulcers; and in the Philippines and South Africa as an oral hypoglycemic agent – but not as a treatment for cancer.[34]

Catharanthus roseus has been a cosmopolitan species since before the Industrial Revolution and the plant's use in folk remedies suggested general bioactivity for diabetes treatment, not cancer. In the mid-eighteenth century, botanist Judith Sumner recorded the arrival of Catharanthus roseus at London's Chelsea Physic Garden from the Jardin des plantes in Paris. It's unclear how the plant first arrived in Paris and the details of its origins in Madagascar beyond reports of its transport from Madagascar by early European explorers. Vincristine was initially distributed at cost to increase accessibility, though later switched to a for-profit model to recover the costs of production and development.

Pharmaceutical bioprospecting

Vincristine and confusion with other drugs in administration

Vincristine has been involved in a number of medical errors. Multiple instances of vincristine having been administered improperly, after having been confused with other drugs, have occurred. If delivered into the spine (intrathecal) it causes paralysis and usually death.

In 2003, two Australian oncology pharmacists recommended a solution. The suggested procedure is to prepare and administer vincristine in a small volume mini-bag rather than a syringe thus physically preventing the vincristine syringe being accidentally attached to a spinal needle. Acceptance of this safer procedure has been slow.[36]

Vincristine

Medical uses

Side effects

Mechanism of action

Chemistry

History

Society and culture

Suppliers

Shortage

Controversy

Pharmaceutical bioprospecting

Pharmaceutical bioprospecting

Vincristine and confusion with other drugs in administration

Research

References

Vincristine and confusion with other drugs in administration