Carmustine#Implants

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| ImageFile = Carmustine.svg

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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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| PubChem = 2578

| ChemSpiderID = 2480

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| UNII = U68WG3173Y

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| EINECS = 205-838-2

| UNNumber = 2811

| DrugBank = DB00262

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| KEGG = D00254

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| MeSHName = Carmustine

| ChEBI = 3423

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 513

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| 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

}}

|Section6={{Chembox Pharmacology

| ATCCode_prefix = L01

| ATCCode_suffix = AD01

| ATC_Supplemental =

| ATCvet =

| Licence_EU = yes

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| Legal_AU = S4

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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}}

| Legal_EU = Rx-only

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| LD50 = 20 mg kg⁻¹ (oral, rat)

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|Section8={{Chembox Related

| OtherFunction_label = ureas

| OtherFunction = 1,3-Dimethylurea

| OtherCompounds = {{unbulleted list|Noxytiolin|1,1,3,3-Tetramethylguanidine|Metformin|Allantoic acid|Buformin}}

}}

{{Infobox drug

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| tradename = BiCNU, Gliadel

| Drugs.com = {{drugs.com|monograph|carmustine}}

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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}}