Carmustine#Implants

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| ImageName = Skeletal formula of carmustine

| ImageFile1 = Carmustine ball-and-stick.png

| ImageName1 = Ball-and-stick model of carmustine molecule

| IUPACName = 1,3-Bis(2-chloroethyl)-1-nitrosourea{{PubChem|2578}}

| OtherNames = N,N'-Bis(2-chloroethyl)-N-nitrosourea, bis-chloroethylnitrosourea, BCNU

|Section1={{Chembox Identifiers

| CASNo = 154-93-8

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| UNNumber = 2811

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| MeSHName = Carmustine

| ChEBI = 3423

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| ChEMBL = 513

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| RTECS = YS2625000

| SMILES = C(CCl)NC(=O)N(CCCl)N=O

| StdInChI = 1S/C5H9Cl2N3O2/c6-1-3-8-5(11)10(9-12)4-2-7/h1-4H2,(H,8,11)

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|Section2={{Chembox Properties

| C=5 | H=9 | Cl=2 | N=3 | O=2

| Appearance = Orange crystals

| Odor = Odourless

| MeltingPtC = 30

| LogP = 1.375

| pKa = 10.194

| pKb = 3.803

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|Section6={{Chembox Pharmacology

| ATCCode_prefix = L01

| ATCCode_suffix = AD01

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| Legal_UK = POM

| Legal_UK_comment = {{cite web | title=Carmustine 100mg Powder and solvent for Solution for Infusion - Summary of Product Characteristics (SmPC) | website=(emc) | date=24 March 2020 | url=https://www.medicines.org.uk/emc/product/11176/smpc }}{{cite web | title=Gliadel 7.7mg Implant - Summary of Product Characteristics (SmPC) | website=(emc) | date=15 June 2020 | url=https://www.medicines.org.uk/emc/product/36/smpc }}

| Legal_US = Rx-only

| Legal_US_comment = {{cite web | title=Bicnu- carmustine kit | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d6cbb63c-e0b1-43ee-ad6f-408da0772079 | access-date=27 February 2021}}{{cite web | title=Gliadel- carmustine wafer | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=38962a55-a514-4c48-bea5-f99a8da4beec | access-date=27 February 2021}}

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| LD50 = 20 mg kg−1 (oral, rat)

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| tradename = BiCNU, Gliadel

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Carmustine, sold under the brand name BiCNU among others, is a medication used mainly for chemotherapy. It is a nitrogen mustard β-chloro-nitrosourea compound used as an alkylating agent.{{cite book | vauthors = Silverman RB, Holladay MW | chapter = Chapter 6 - DNA-Interactive Agents |date= January 2014 | title = The Organic Chemistry of Drug Design and Drug Action | edition = Third |pages=275–331 | veditors = Silverman RB, Holladay MW |place=Boston |publisher=Academic Press |language=en |doi=10.1016/b978-0-12-382030-3.00006-4 |isbn=978-0-12-382030-3 }}

Description

Carmustine is an orange-yellow solid medication used mainly for chemotherapy. It is a nitrogen mustard β-chloro-nitrosourea compound.{{cite book | vauthors = Rider BJ | chapter = Carmustine |date= January 2007 | veditors = Enna SJ, Bylund DB | title = xPharm: The Comprehensive Pharmacology Reference |pages=1–4 |place=New York |publisher=Elsevier |language=en |doi=10.1016/b978-008055232-3.61389-3 |isbn=978-0-08-055232-3 }}

Mechanism of action

As an alkylating agent, carmustine can form interstrand crosslinks in DNA, which prevents DNA replication and DNA transcription.{{Citation |title=NLM PubChem CID Index |work=Vitamin D Handbook |year=2007 |pages=239–244 |place=Hoboken, NJ, USA |publisher=John Wiley & Sons, Inc. |doi=10.1002/9780470238165.indsp1 |isbn=9780470238165 |doi-access=free }}

Uses

Carmustine is used as an alkylating agent to treat several types of brain cancer including glioma, glioblastoma multiforme, medulloblastoma and astrocytoma, multiple myeloma, and lymphoma (Hodgkin's and non-Hodgkin).

Carmustine is sometimes used in conjunction with alkyl guanine transferase (AGT) inhibitors, such as O6-benzylguanine. The AGT-inhibitors increase the efficacy of carmustine by inhibiting the direct reversal pathway of DNA repair, which will prevent formation of the interstrand crosslink between the N1 of guanine and the N3 of cytosine.

It is also used as part of a chemotherapeutic protocol in preparation for hematological stem cell transplantation, a type of bone marrow transplant, in order to reduce the white blood cell count in the recipient.{{cite journal | vauthors = Damaj G, Cornillon J, Bouabdallah K, Gressin R, Vigouroux S, Gastinne T, Ranchon F, Ghésquières H, Salles G, Yakoub-Agha I, Gyan E | title = Carmustine replacement in intensive chemotherapy preceding reinjection of autologous HSCs in Hodgkin and non-Hodgkin lymphoma: a review | journal = Bone Marrow Transplantation | volume = 52 | issue = 7 | pages = 941–949 | date = July 2017 | pmid = 28112752 | doi = 10.1038/bmt.2016.340 | doi-access = free }} Use under this protocol, usually with fludarabine and melphalan, was developed by oncologists at the University of Texas MD Anderson Cancer Center.{{citation needed|date=February 2018}}

Implants

In the treatment of brain tumours, the U.S. Food and Drug Administration (FDA) approved biodegradable discs infused with carmustine (Gliadel).{{cite journal | vauthors = Ewend MG, Brem S, Gilbert M, Goodkin R, Penar PL, Varia M, Cush S, Carey LA | title = Treatment of single brain metastasis with resection, intracavity carmustine polymer wafers, and radiation therapy is safe and provides excellent local control | journal = Clinical Cancer Research | volume = 13 | issue = 12 | pages = 3637–3641 | date = June 2007 | pmid = 17575228 | doi = 10.1158/1078-0432.CCR-06-2095 | doi-access = | s2cid = 14016432 }} They are implanted under the skull during a surgery called a craniotomy. The disc allows for controlled release of carmustine in the extracellular fluid of the brain, thus eliminating the need for the encapsulated drug to cross the blood-brain barrier.{{cite web|url=http://www.hopkinsmedicine.org/hmn/W05/feature3.cfm|title=Hopkins Medicine Magazine - In Spite of All Odds|access-date=2014-07-08|archive-url=https://web.archive.org/web/20141120001145/http://www.hopkinsmedicine.org/hmn/W05/feature3.cfm|archive-date=2014-11-20|url-status=dead}}

Production

Carmustine for injection was marketed under the name BiCNU by Bristol-Myers Squibb{{cite web|url=https://www.bms.com/life-and-science.html |title=Company Statement on BiCNU® (carmustine for injection) | publisher = Bristol-Myers Squibb Company |access-date=2015-01-31 |url-status=dead |archive-url=https://web.archive.org/web/20140711101801/https://www.bms.com/life-and-science.html |archive-date=2014-07-11 }} and now{{when|date=December 2017}} by Emcure Pharmaceuticals.{{Cite web |url=http://www.emcure.co.in/news/docs/BiCNU%20Emcure%20press%20release.pdf |title=Emcure Press release |access-date=2015-01-31 |archive-url=https://web.archive.org/web/20140702050137/http://emcure.co.in/news/docs/BiCNU%20Emcure%20press%20release.pdf |archive-date=2014-07-02 |url-status=dead }} In India it is sold under various brand names, including Consium.{{citation needed|date=December 2017}}. The product is available as a generic version with other manufacturers offering the product licensed in the US and EU markets.{{citation needed|date=February 2021}}

See also

References

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