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==Route of administration==
==Route of administration==
Daunorubicin should only be administered in a rapid [[intravenous infusion]]. It should not be administered [[intramuscular]]ly or [[subcutaneous]]ly, since it may cause extensive tissue [[necrosis]].
Daunorubicin should only be administered in a rapid [[intravenous infusion]]. It should not be administered [[intramuscular]]ly or [[subcutaneous]]ly, since it may cause extensive tissue [[necrosis]].
It should also '''never''' be administered [[intrathecal]]ly (into the [[spinal canal]]), as this will cause extensive damage to the [[nervous system]] and may lead to [[death]].<ref> Daunorubicin has been used intravitreally (inside the eye) for the purposes of preventing proliferative vitreoretinopathy, a common complication following retinal detachment surgery, but has not been found to be effective and is not used for any other ophthalmic purposes at this time.
It should also '''never''' be administered [[intrathecal]]ly (into the [[spinal canal]]), as this will cause extensive damage to the [[nervous system]] and may lead to [[death]]. Daunorubicin has been used intravitreally (inside the eye) for the purposes of preventing proliferative vitreoretinopathy, a common complication following retinal detachment surgery, but has not been found to be effective and is not used for any other ophthalmic purposes at this time.<ref> {{cite journal | author= Mortensen, ME ''et al.'' | title= Inadvertent intrathecal injection of daunorubicin with fatal outcome | journal= [http://www3.interscience.wiley.com/cgi-bin/jhome/32390?CRETRY=1&SRETRY=0 Med Pediatr Oncol]| year= 1992 | volume= 20 | issue= 3 | pages= 249–253 | pmid= 1574039}}</ref>
{{cite journal | author= Mortensen, ME ''et al.'' | title= Inadvertent intrathecal injection of daunorubicin with fatal outcome | journal= [http://www3.interscience.wiley.com/cgi-bin/jhome/32390?CRETRY=1&SRETRY=0 Med Pediatr Oncol]| year= 1992 | volume= 20 | issue= 3 | pages= 249–253 | pmid= 1574039}}</ref>


==References==
==References==

Revision as of 14:08, 13 October 2013

Daunorubicin
Clinical data
Trade namesCerubidine
AHFS/Drugs.comMonograph
MedlinePlusa682289
Pregnancy
category
Routes of
administration		Exclusively intravenous. Causes severe necrosis if administered intramuscularly or subcutaneously
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismHepatic
Elimination half-life26.7 hours (metabolite)
ExcretionBiliary and urinary
Identifiers
  • (8S,10S)-8-acetyl-10-[(2S,4S,5S,6S)-
    4-amino-5-hydroxy-6-methyl-oxan-
    2-yl]oxy-6,8,11-trihydroxy-1-methoxy-
    9,10-dihydro-7H-tetracene-5,12-dione
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.040.048 Edit this at Wikidata
Chemical and physical data
FormulaC27H29NO10
Molar mass527.52 g/mol
563.99 g/mol (HCl salt) g·mol−1
3D model (JSmol)
  • C[C@H]1[C@H]([C@H](C[C@@H](O1)O[C@H]2C[C@@](Cc3c2c(c4c(c3O)C(=O)c5cccc(c5C4=O)OC)O)(C(=O)C)O)N)O
  • InChI=1S/C27H29NO10/c1-10-22(30)14(28)7-17(37-10)38-16-9-27(35,11(2)29)8-13-19(16)26(34)21-20(24(13)32)23(31)12-5-4-6-15(36-3)18(12)25(21)33/h4-6,10,14,16-17,22,30,32,34-35H,7-9,28H2,1-3H3/t10-,14-,16-,17-,22+,27-/m0/s1 checkY
  • Key:STQGQHZAVUOBTE-VGBVRHCVSA-N checkY
  (verify)

Daunorubicin or daunomycin (daunomycin cerubidine) is chemotherapeutic of the anthracycline family that is given as a treatment for some types of cancer. It is most commonly used to treat specific types of leukaemia (acute myeloid leukemia and acute lymphocytic leukemia). It was initially isolated from Streptomyces peucetius.

A liposomal formulation of daunorubicin is marketed in the United States as DaunoXome.

History

See also: Doxorubicin § History, and History of cancer chemotherapy

In the 1950s, an Italian research company, Farmitalia Research Laboratories, began an organized effort to isolate anticancer compounds from soil-based microbes. A soil sample was isolated from the area surrounding the Castel del Monte, a 13th-century castle in Apulia. A new strain of Streptomyces peucetius which produced a red pigment was isolated, and an antibiotic was produced from this bacterium that was found to have good activity against murine tumors. Since a group of French researchers discovered the same compound at about the same time, the two teams named the compound daunorubicin, combining the name Dauni, a pre-Roman tribe that occupied the area of Italy where the compound was isolated, with the French word for ruby, rubis, describing the color.[1] Clinical trials began in the 1960s, and the drug saw success in treating acute leukemia and lymphoma. However, by 1967, it was recognized that daunorubicin could produce fatal cardiac toxicity.[2]

Uses

It slows or stops the growth of cancer cells in the body. Treatment is usually performed together with other chemotherapy drugs (such as cytarabine), and its administration depends on the type of tumor and the degree of response.

In addition to its major use in treating AML, daunorubicin is also used to treat neuroblastoma. Daunorubicin has been used with other chemotherapy agents to treat the blastic phase of chronic myelogenous leukemia.

Daunorubicin is also used as the starting material for semi-synthetic manufacturing of doxorubicin, epirubicin and idarubicin.

Mechanism of action

Cartoon diagram of two doxorubicin molecules intercalating DNA, [3]

Similar to Doxorubicin, Daunorubicin interacts with DNA by intercalation and inhibition of macromolecular biosynthesis.[4][5] This inhibits the progression of the enzyme topoisomerase II, which relaxes supercoils in DNA for transcription. Daunorubicin stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being resealed and thereby stopping the process of replication. On binding to DNA, daunomycin intercalates, with its daunosamine residue directed toward the minor groove. It has the highest preference for two adjacent G/C base pairs flanked on the 5' side by an A/T base pair. Daunomycin effectively binds to every 3 base pairs and induces a local unwinding angle of 11°, but negligible distortion of helical conformation.[6] It can also induce histone eviction from chromatin upon intercalation.[7]

Route of administration

Daunorubicin should only be administered in a rapid intravenous infusion. It should not be administered intramuscularly or subcutaneously, since it may cause extensive tissue necrosis. It should also never be administered intrathecally (into the spinal canal), as this will cause extensive damage to the nervous system and may lead to death. Daunorubicin has been used intravitreally (inside the eye) for the purposes of preventing proliferative vitreoretinopathy, a common complication following retinal detachment surgery, but has not been found to be effective and is not used for any other ophthalmic purposes at this time.[8]

References

  1. ^ Weiss RB (1992). "The anthracyclines: will we ever find a better doxorubicin?". Seminars in Oncology. 19 (6): 670–86. PMID 1462166. {{cite journal}}: Unknown parameter |month= ignored (help)
  2. ^ Tan C, Tasaka H, Yu KP, Murphy ML, Karnofsky DA (1967). "Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia". Cancer. 20 (3): 333–53. doi:10.1002/1097-0142(1967)20:3<333::AID-CNCR2820200302>3.0.CO;2-K. PMID 4290058. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ http://www.rcsb.org/pdb/explore.do?structureId=1D12
  4. ^ Fornari FA, Randolph JK, Yalowich JC, Ritke MK, Gewirtz DA (1994). "Interference by doxorubicin with DNA unwinding in MCF-7 breast tumor cells". Mol Pharmacol. 45 (4): 649–56. PMID 8183243. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ Momparler RL, Karon M, Siegel SE, Avila F (1976). "Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells". Cancer Res. 36 (8): 2891–5. PMID 1277199. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  6. ^ G J Quigley, A H Wang, G Ughetto, G van der Marel, J H van Boom, and A Rich (1980). "Molecular structure of an anticancer drug-DNA complex: daunomycin plus d(CpGpTpApCpG)". PNAS. 77 (12): 7204–7208. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  7. ^ Pang B, Qiao X, Janssen L, Velds A, Groothuis T, Kerkhoven R, Nieuwland M, Ovaa H, Rottenberg S, van Tellingen O, Janssen J, Huijgens P, Zwart W, Neefjes J (2013). "Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin". Nature Communications. 4: 1908. doi:10.1038/ncomms2921. PMID 23715267.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Mortensen, ME; et al. (1992). "Inadvertent intrathecal injection of daunorubicin with fatal outcome". Med Pediatr Oncol. 20 (3): 249–253. PMID 1574039. {{cite journal}}: Explicit use of et al. in: |author= (help); External link in |journal= (help)
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