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Identification
Name Carboplatin
Accession Number DB00958 (APRD00466)
Type small molecule
Groups approved
Description

An organoplatinum compound that possesses antineoplastic activity. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
CBDCA
cis-Diammine(1,1-cyclobutanedicarboxylato)platinum(II)
Salts Not Available
Brand names
Name Company
Paraplatin
Paraplatin-AQ
Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Cross-Linking Reagents
CAS number 41575-94-4
Weight Average: 371.254
Monoisotopic: 371.044481331
Chemical Formula C6H12N2O4Pt
InChI Key InChIKey=OLESAACUTLOWQZ-UHFFFAOYSA-L
InChI
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
Plain Text
IUPAC Name
6,8-dioxa-7-platinaspiro[3.5]nonane-5,9-dione diamine
SMILES
N.N.O=C1O[Pt]OC(=O)C11CCC1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Carbonyl Compounds
  • Keto-Acids
  • Dicarboxylic Acids
Substructures
  • Carbonyl Compounds
  • Hydroxy Compounds
  • Anions
  • Acetates
  • Keto-Acids
  • Carboxylic Acids and Derivatives
  • Cyclobutane and Derivatives
  • Dicarboxylic Acids
Pharmacology
Indication For the initial treatment of advanced ovarian carcinoma in established combination with other approved chemotherapeutic agents. One established combination regimen consists of PARAPLATIN and cyclophosphamide.
Pharmacodynamics Carboplatin is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.
Mechanism of action Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.
Absorption Not Available
Volume of distribution
  • 16 L
Protein binding Very low
Metabolism Not Available
Route of elimination The major route of elimination of carboplatin is renal excretion.
Half life 1.1-2 hours
Clearance
  • 4.4 L/h [Patients with Clcr >= 60 mL/min receiving IV infusion of 300 to 500 mg/m2]
Toxicity Toxic by ingestion. May be create toxic effect through inhalation or skin contact. May cause reproductive defects. May act as a sensitizer. ORL-RAT LD50 343 mg kg-1; SCN-RAT LD50 72 mg kg-1; IPN-MUS LD50 118 mg kg-1
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • Pliva inc
  • Sandoz inc
  • Watson laboratories inc
  • Watson laboratories
  • Bristol myers squibb co pharmaceutical research institute
  • Akorn inc
  • Bedford laboratories
  • Bioniche pharma usa llc
  • Ebewe pharma ges mbh nfg kg
  • Fresenius kabi oncology plc
  • Pharmachemie bv
  • Pliva lachema as
  • Spectrum pharmaceuticals inc
  • Sun pharma global inc
  • Teva parenteral medicines inc
  • Bristol myers squibb co
Packagers
Dosage forms
Form Route Strength
Liquid Intravenous
Solution Intravenous
Prices
Unit description Cost Unit
Paraplatin 450 mg vial 1474.46 USD vial
Paraplatin 150 mg vial 491.48 USD vial
Carboplatin 150 mg vial 255.31 USD vial
Paraplatin 50 mg vial 163.84 USD vial
Carboplatin 450 mg vial 156.25 USD vial
Carboplatin 50 mg vial 85.1 USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties Not Available
Predicted Properties
Property Value Source
logP 1.06 ChemAxon
pKa (strongest basic) -6.6 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 52.6 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 29.01 ChemAxon
polarizability 14.06 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Natarajan G, Malathi R, Holler E: Increased DNA-binding activity of cis-1,1-cyclobutanedicarboxylatodiammineplatinum(II) (carboplatin) in the presence of nucleophiles and human breast cancer MCF-7 cell cytoplasmic extracts: activation theory revisited. Biochem Pharmacol. 1999 Nov 15;58(10):1625-9. Pubmed
  2. Knox RJ, Friedlos F, Lydall DA, Roberts JJ: Mechanism of cytotoxicity of anticancer platinum drugs: evidence that cis-diamminedichloroplatinum(II) and cis-diammine-(1,1-cyclobutanedicarboxylato)platinum(II) differ only in the kinetics of their interaction with DNA. Cancer Res. 1986 Apr;46(4 Pt 2):1972-9. Pubmed
  3. Canetta R, Rozencweig M, Carter SK: Carboplatin: the clinical spectrum to date. Cancer Treat Rev. 1985 Sep;12 Suppl A:125-36. Pubmed
External Links
Resource Link
KEGG Drug D01363 Link_out
PubChem Compound 38904 Link_out
PubChem Substance 46507170 Link_out
ChemSpider 436073 Link_out
ChEBI 31355 Link_out
ChEMBL 31355 Link_out
Therapeutic Targets Database DAP000535 Link_out
PharmGKB PA448803 Link_out
Drug Product Database 2126680 Link_out
RxList http://www.rxlist.com/cgi/generic3/carboplat.htm Link_out
Drugs.com http://www.drugs.com/cdi/carboplatin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Carboplatin Link_out
ATC Codes
  • L01XA02
AHFS Codes
  • 10:00.00
PDB Entries Not Available
FDA label show (1.26 MB)
MSDS show (73.5 KB)
Interactions
Drug Interactions
Drug Interaction
Bendamustine Increases toxicity through pharmacodynamic synergism. Additive myelosuppression.
Docetaxel Platinum derivatives such as carboplatin may enhance the myelosuppressive effect of taxane derivatives such as docetaxel. Administer taxane derivative before platinum derivative when given as sequential infusions to limit toxicity. Administering the taxane derivative before the platinum derivative seems prudent.
Fosphenytoin The antineoplasic agent decreases the effect of hydantoin
Leflunomide Immunosuppressants such as carboplatin may enhance the adverse/toxic effect of leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Consider eliminating the use of a leflunomide loading dose in patients who are receiving other immunosuppressants in order to reduce the risk for serious adverse events such as hematologic toxicity. Also, patients receiving both leflunomide and another immunosuppressive medication should be monitored for bone marrow suppression at least monthly throughout the duration of concurrent therapy.
Natalizumab Immunosuppressants such as natalizumab may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.
Paclitaxel Platinum derivatives such as carboplatin may enhance the myelosuppressive effect of taxane derivatives such as paclitaxel. Administer taxane derivative before platinum derivative when given as sequential infusions to limit toxicity. Administering the taxane derivative before the platinum derivative seems prudent.
Phenytoin The antineoplasic agent decreases the effect of hydantoin
Pimecrolimus Pimecrolimus may enhance the adverse/toxic effect of immunosuppressants such as carboplatin. Avoid use of pimecrolimus cream in patients receiving immunosuppressants.
Roflumilast Roflumilast may enhance the immunosuppressive effect of immunosuppressants such as carboplatin. he Canadian roflumilast product monograph recommends avoiding concurrent use of roflumilast with any immunosuppressant medications due to the antiinflammatory/immune altering effects of roflumilast and the lack of relevant clinical experience with such use. Of note, this recommendation to avoid concurrent use does not apply to either inhaled corticosteroids (which have much more limited systemic immune-suppressing actions) or short-term systemic corticosteroid use. U.S. prescribing information does not contain this warning; but it appears prudent to avoid this combination when possible.
Sorafenib Sorafenib may enhance the adverse/toxic effect of carboplatin. Concurrent use of sorafenib with carboplatin and placlitaxel in patients with squamous cell lung cancer is contraindicated. The use of this combination in other settings is not specifically contraindicated, but any such use should be approached with added caution.
Tacrolimus Tacrolimus (Topical) may enhance the adverse/toxic effect of immunosuppressants such as carboplatin. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.
Topotecan Administration of Topotecan after Carboplatin therapy may increase the risk of hematologic toxicity, such as neutropenia and/or thrombocytopenia. A dose adjustment may be required or the sequence of administration reversed.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food Interactions
  • Avoid echinacea as it may decrease effectiveness of immunosuppresants like carboplatin
Targets

1. DNA

Pharmacological action: yes
Actions: cross-linking/alkylation

DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

Gene Sequence: FASTA

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Sharma S, Gong P, Temple B, Bhattacharyya D, Dokholyan NV, Chaney SG: Molecular Dynamic Simulations of Cisplatin- and Oxaliplatin-d(GG) Intrastand Cross-links Reveal Differences in their Conformational Dynamics. J Mol Biol. 2007 Aug 23;. Pubmed
  4. Appleton K, Mackay HJ, Judson I, Plumb JA, McCormick C, Strathdee G, Lee C, Barrett S, Reade S, Jadayel D, Tang A, Bellenger K, Mackay L, Setanoians A, Schatzlein A, Twelves C, Kaye SB, Brown R: Phase I and pharmacodynamic trial of the DNA methyltransferase inhibitor decitabine and carboplatin in solid tumors. J Clin Oncol. 2007 Oct 10;25(29):4603-9. Pubmed
Enzymes

1. Xanthine dehydrogenase/oxidase

Actions: inducer

This enzyme can be converted from the dehydrogenase form (D) to the oxidase form (O) irreversibly by proteolysis or reversibly through the oxidation of sulfhydryl groups

UniProt ID: P47989 Link_out
Gene: XDH Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Husai K, Jagannathan R, Hasan Z, Trammell GL, Rybak LP, Hazelrigg SR, Somani SM: Dose response of carboplatin-induced nephrotoxicity in rats. Pharmacol Toxicol. 2002 Aug;91(2):83-9. Pubmed
  2. Husain K, Whitworth C, Rybak LP: Time response of carboplatin-induced nephrotoxicity in rats. Pharmacol Res. 2004 Sep;50(3):291-300. Pubmed
  3. Husain K, Whitworth C, Somani SM, Rybak LP: Carboplatin-induced oxidative stress in rat cochlea. Hear Res. 2001 Sep;159(1-2):14-22. Pubmed
  4. Husain K, Whitworth C, Hazelrigg S, Rybak L: Carboplatin-induced oxidative injury in rat inferior colliculus. Int J Toxicol. 2003 Sep-Oct;22(5):335-42. Pubmed
Transporters

1. High affinity copper uptake protein 1

Actions: substrate

Involved in high-affinity copper uptake

UniProt ID: O15431 Link_out
Gene: SLC31A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Howell SB, Safaei R, Larson CA, Sailor MJ: Copper transporters and the cellular pharmacology of the platinum-containing cancer drugs. Mol Pharmacol. 2010 Jun;77(6):887-94. Epub 2010 Feb 16. Pubmed
  2. Song IS, Savaraj N, Siddik ZH, Liu P, Wei Y, Wu CJ, Kuo MT: Role of human copper transporter Ctr1 in the transport of platinum-based antitumor agents in cisplatin-sensitive and cisplatin-resistant cells. Mol Cancer Ther. 2004 Dec;3(12):1543-9. Pubmed

2. Probable low affinity copper uptake protein 2

Actions: substrate

Involved in low-affinity copper uptake (Potential)

UniProt ID: O15432 Link_out
Gene: SLC31A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Blair BG, Larson CA, Safaei R, Howell SB: Copper transporter 2 regulates the cellular accumulation and cytotoxicity of Cisplatin and Carboplatin. Clin Cancer Res. 2009 Jul 1;15(13):4312-21. Epub 2009 Jun 9. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19