Carboplatin

Source: Wikipedia, the free encyclopedia.
Carboplatin
Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailabilitycomplete
Protein bindingVery low
Elimination half-life1.1-2 hours
ExcretionKidney
Identifiers
  • cis-diammine(cyclobutane-1,1-dicarboxylate-O,O')platinum(II)
JSmol)
  • C1CC2(C1)C(=O)O[Pt-2]([NH3+])([NH3+])OC2=O
  • InChI=1S/C6H8O4.2H3N.Pt/c7-4(8)6(5(9)10)2-1-3-6;;;/h1-3H2,(H,7,8)(H,9,10);2*1H3;/q;;;+2/p-2 checkY
  • Key:OLESAACUTLOWQZ-UHFFFAOYSA-L checkY
 ☒NcheckY (what is this?)  (verify)

Carboplatin, sold under the brand name Paraplatin among others, is a

injection into a vein.[3]

Side effects generally occur.

carcinogenic, but further research is needed to confirm this.[3] Use during pregnancy may result in harm to the baby.[3] Carboplatin is in the platinum-based antineoplastic family of medications and works by interfering with duplication of DNA.[3][5]

Carboplatin was developed as a less toxic analogue of cisplatin.[6] It was patented in 1972 and approved for medical use in 1989.[7] It is on the 2023 World Health Organization's List of Essential Medicines.[8]

Medical uses

Carboplatin is used to treat a number of forms of

brain cancer, and neuroblastoma. It may be used for some types of testicular cancer but cisplatin is generally more effective.[3] It has also been used to treat triple-negative breast cancer
.

Side effects

Relative to cisplatin, the greatest benefit of carboplatin is its reduced side effects, particularly the elimination of nephrotoxic effects. Nausea and vomiting are less severe and more easily controlled.[9]

The main drawback of carboplatin is its myelosuppressive effect. This causes the

myelosuppression usually occurs 21–28 days after the first treatment, after which the blood cell and platelet levels in the blood begin to stabilize, often coming close to its pre-carboplatin levels. This decrease in white blood cells (neutropenia) can cause complications, and is sometimes treated with drugs like filgrastim. The most notable complication of neutropenia is increased probability of infection by opportunistic organisms, which necessitates hospital readmission and treatment with antibiotics
.

Mechanism of action

Carboplatin differs from cisplatin in that it has a

alkylating agents. CBDCA and chloride are the leaving groups in these respective drugs Carboplatin exhibits slower aquation (replacement of CBDCA by water) and thus slower DNA binding kinetics, although it forms the same reaction products in vitro at equivalent doses with cisplatin. Unlike cisplatin, carboplatin may be susceptible to alternative mechanisms. Some results show that cisplatin and carboplatin cause different morphological changes in MCF-7 cell lines while exerting their cytotoxic behaviour.[10]
The diminished reactivity limits protein-carboplatin complexes, which are excreted. The lower excretion rate of carboplatin means that more is retained in the body, and hence its effects are longer lasting (a retention half-life of 30 hours for carboplatin, compared to 1.5-3.6 hours in the case of cisplatin).

Like cisplatin, carboplatin binds to and cross-links DNA, interfering with the replication and suppressing growth of the cancer cell.[11][12]

Dose

Calvert's formula is used to calculate the dose of carboplatin. It considers the creatinine clearance and the desired

kidney function.[14]

Calvert formula:

The typical area under the curve (AUC) for carboplatin ranges from 3-7 (mg/ml)*min.[14]

Synthesis

Cisplatin reacts with silver nitrate and then cyclobutan-1,1-dicarboxylic acid to form carboplatin.[15]

History

Carboplatin, a cisplatin analogue, was developed by

Institute of Cancer Research in order to reduce the toxicity of cis platin.[6][16] It gained U.S. Food and Drug Administration
(FDA) approval for carboplatin, under the brand name Paraplatin, in March 1989. Starting in October 2004, generic versions of the drug became available.

Research

Carboplatin has also been used for

radiotherapy for this treatment, while having fewer side effects.[17] This has led to carboplatin based adjuvant therapy being generally preferred over adjuvant radiotherapy in clinical practice.[18]

Carboplatin combined with

liposolubility and PEGylation. This is useful in chemotherapy, specifically non-small cell lung cancer.[19]

References

  1. FDA
    . Retrieved 22 Oct 2023.
  2. ^ "Product monograph brand safety updates". Health Canada. 7 July 2016. Retrieved 3 April 2024.
  3. ^ a b c d e f g h i "Carboplatin". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
  4. PMID 29632935
    .
  5. PMID 26113607
    .
  6. ^
    PMID 9893623
    .
  7. ISBN 9783527607495. Archived
    from the original on 2016-12-20.
  8. hdl:10665/371090
    . WHO/MHP/HPS/EML/2023.02.
  9. ISBN 9780323798334
    .
  10. PMID 10535754
    .
  11. PMID 16464006
    .
  12. ISBN 9780123708793
    .
  13. ^ O'Cearbhaill R, Sabbatini PS (September 1, 2012). "New Guidelines for Carboplatin Dosing". Memorial Sloan Kettering Cancer Center. Archived from the original on 2014-10-31. Retrieved 2014-03-27.
  14. ^
    PMID 2681557
    .
  15. ISBN 9780444521668
    .
  16. ^ "Discovering early chemotherapy drugs". Institute of Cancer Research. Retrieved 2023-10-06.
  17. S2CID 6001898
    .
  18. S2CID 8072355
    .
  19. PMID 34176381
    .

Further reading
Retrieved from "https://en.wikipedia.org/w/index.php?title=Carboplatin&oldid=1216992748"