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Identification
NameCarboplatin
Accession NumberDB00958  (APRD00466)
Typesmall molecule
Groupsapproved
Description

An organoplatinum compound that possesses antineoplastic activity. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
CarboplatinNot AvailableNot Available
CBDCANot AvailableNot Available
cis-(1,1-Cyclobutanedicarboxylato)diammineplatinum(ii)Not AvailableNot Available
cis-Diammine(1,1-cyclobutanedicarboxylato)platinumNot AvailableNot Available
cis-Diammine(1,1-cyclobutanedicarboxylato)platinum(II)Not AvailableNot Available
ParaplatinNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
ParaplatinNot Available
Paraplatin-AQNot Available
Brand mixturesNot Available
Categories
CAS number41575-94-4
WeightAverage: 371.254
Monoisotopic: 371.044481331
Chemical FormulaC6H12N2O4Pt
InChI KeyOLESAACUTLOWQZ-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
IUPAC Name
6,8-dioxa-7-platinaspiro[3.5]nonane-5,9-dione diamine
SMILES
N.N.O=C1O[Pt]OC(=O)C11CCC1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganonitrogen Compounds
ClassAmines
SubclassPolyamines
Direct parentPolyamines
Alternative parentsMetalloheterocyclic Compounds; Carboxylic Acids and Derivatives
SubstituentsNot Available
Classification descriptionThis compound belongs to the polyamines. These are compounds containing more than one amine group.
Pharmacology
IndicationFor the initial treatment of advanced ovarian carcinoma in established combination with other approved chemotherapeutic agents. One established combination regimen consists of PARAPLATIN and cyclophosphamide. It is also indicated for the palliative treatment of patients with ovarian carcinoma recurrent after prior chemotherapy, including patients who have been previously treated with cisplatin.
PharmacodynamicsCarboplatin 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 actionAlkylating 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.
AbsorptionThe Cmax values and areas under the plasma concentration versus time curves from 0 to infinity (AUC inf) increase linearly with dose, although the increase was slightly more than dose proportional. Carboplatin exhibits linear pharmacokinetics.
Volume of distribution
  • 16 L [apparent volume of distribution, 30 minute IV infusion of 300 mg/m^2 to 500 mg/m^2]
Protein bindingCarboplatin is not bound to plasma protein. However, the platinum itself from carboplatin irreversibly binds to plasma proteins and is slowly eliminated with a minimum half-life of 5 days.
Metabolism
Route of eliminationThe major route of elimination of carboplatin is renal excretion. After 24 hours, all of the platinum is recovered in the urine as carboplatin. Whether biliary excretion occurs is not known.
Half lifeInitial plasma half-life (alpha) = 1.1 to 2 hours; Post distribution plasma half-life (beta) = 2.6 - 5.9 hours.
Clearance
  • 4.4 L/hour [total body clearance, 30 minute IV infusion of 300 mg/m^2 to 500 mg/m^2]
ToxicityToxic 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.6183
Blood Brain Barrier + 0.8295
Caco-2 permeable - 0.584
P-glycoprotein substrate Non-substrate 0.6375
P-glycoprotein inhibitor I Non-inhibitor 0.9489
P-glycoprotein inhibitor II Non-inhibitor 0.9968
Renal organic cation transporter Non-inhibitor 0.9239
CYP450 2C9 substrate Non-substrate 0.8745
CYP450 2D6 substrate Non-substrate 0.8276
CYP450 3A4 substrate Non-substrate 0.703
CYP450 1A2 substrate Non-inhibitor 0.8142
CYP450 2C9 substrate Non-inhibitor 0.854
CYP450 2D6 substrate Non-inhibitor 0.9168
CYP450 2C19 substrate Non-inhibitor 0.8607
CYP450 3A4 substrate Non-inhibitor 0.6995
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9896
Ames test Non AMES toxic 0.746
Carcinogenicity Non-carcinogens 0.8906
Biodegradation Ready biodegradable 0.8235
Rat acute toxicity 2.3469 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9596
hERG inhibition (predictor II) Non-inhibitor 0.9767
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
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous150 mg
Injection, solutionIntravenous50 mg/5 mL; 150 mg/15 mL; 450 mg/45 mL; 600 mg/60 mL
Prices
Unit descriptionCostUnit
Paraplatin 450 mg vial1474.46USDvial
Paraplatin 150 mg vial491.48USDvial
Carboplatin 150 mg vial255.31USDvial
Paraplatin 50 mg vial163.84USDvial
Carboplatin 450 mg vial156.25USDvial
Carboplatin 50 mg vial85.1USDvial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
logP1.06ChemAxon
pKa (strongest basic)-6.6ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count0ChemAxon
polar surface area52.6ChemAxon
rotatable bond count0ChemAxon
refractivity29.01ChemAxon
polarizability14.06ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Jingzun Wang, Huisheng Qu, Lei Wang, Ting Wang, “Supermolecular carboplatin derivatives, their preparation and pharmaceutical composition containing them as active ingredient and applications of the compositions.” U.S. Patent US07259270, issued August 21, 2007.

US07259270
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
ResourceLink
KEGG DrugD01363
PubChem Compound38904
PubChem Substance46507170
ChemSpider436073
ChEBI31355
ChEMBLCHEMBL1351
Therapeutic Targets DatabaseDAP000535
PharmGKBPA448803
Drug Product Database2126680
RxListhttp://www.rxlist.com/cgi/generic3/carboplat.htm
Drugs.comhttp://www.drugs.com/cdi/carboplatin.html
WikipediaCarboplatin
ATC CodesL01XA02
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelshow(1.26 MB)
MSDSshow(73.5 KB)
Interactions
Drug Interactions
Drug
BendamustineIncreases toxicity through pharmacodynamic synergism. Additive myelosuppression.
DocetaxelPlatinum 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.
FosphenytoinThe antineoplasic agent decreases the effect of hydantoin
LeflunomideImmunosuppressants 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.
NatalizumabImmunosuppressants 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.
PaclitaxelPlatinum 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.
PhenytoinThe antineoplasic agent decreases the effect of hydantoin
PimecrolimusPimecrolimus may enhance the adverse/toxic effect of immunosuppressants such as carboplatin. Avoid use of pimecrolimus cream in patients receiving immunosuppressants.
RoflumilastRoflumilast 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.
SorafenibSorafenib 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.
TacrolimusTacrolimus (Topical) may enhance the adverse/toxic effect of immunosuppressants such as carboplatin. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.
TopotecanAdministration 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.
TrastuzumabTrastuzumab 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

Kind: nucleotide

Organism: Human

Pharmacological action: yes

Actions: cross-linking/alkylation

Components

Name UniProt ID Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Xanthine dehydrogenase/oxidase P47989 Details

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

2. Myeloperoxidase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Myeloperoxidase P05164 Details

References:

  1. https://www.pharmgkb.org/pathway/PA150642262#

3. Glutathione S-transferase theta-1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Glutathione S-transferase theta-1 P30711 Details

References:

  1. https://www.pharmgkb.org/pathway/PA150642262#

4. Metallothionein-1A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Metallothionein-1A P04731 Details

References:

  1. https://www.pharmgkb.org/pathway/PA150642262#

5. Metallothionein-2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Metallothionein-2 P02795 Details

References:

  1. https://www.pharmgkb.org/pathway/PA150642262#

6. Superoxide dismutase [Cu-Zn]

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Superoxide dismutase [Cu-Zn] P00441 Details

References:

  1. https://www.pharmgkb.org/pathway/PA150642262#

7. Glutathione S-transferase P

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Glutathione S-transferase P P09211 Details

References:

  1. https://www.pharmgkb.org/pathway/PA150642262#

8. Glutathione S-transferase Mu 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Glutathione S-transferase Mu 1 P09488 Details

References:

  1. https://www.pharmgkb.org/pathway/PA150642262#

9. NAD(P)H dehydrogenase [quinone] 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
NAD(P)H dehydrogenase [quinone] 1 P15559 Details

References:

  1. https://www.pharmgkb.org/pathway/PA150642262#

Transporters

1. High affinity copper uptake protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
High affinity copper uptake protein 1 O15431 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Probable low affinity copper uptake protein 2 O15432 Details

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

3. Copper-transporting ATPase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Copper-transporting ATPase 1 Q04656 Details

References:

  1. Samimi G, Katano K, Holzer AK, Safaei R, Howell SB: Modulation of the cellular pharmacology of cisplatin and its analogs by the copper exporters ATP7A and ATP7B. Mol Pharmacol. 2004 Jul;66(1):25-32. Pubmed

4. Copper-transporting ATPase 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Copper-transporting ATPase 2 P35670 Details

References:

  1. Samimi G, Katano K, Holzer AK, Safaei R, Howell SB: Modulation of the cellular pharmacology of cisplatin and its analogs by the copper exporters ATP7A and ATP7B. Mol Pharmacol. 2004 Jul;66(1):25-32. Pubmed

5. ATP-binding cassette sub-family G member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

References:

  1. Ceckova M, Vackova Z, Radilova H, Libra A, Buncek M, Staud F: Effect of ABCG2 on cytotoxicity of platinum drugs: interference of EGFP. Toxicol In Vitro. 2008 Dec;22(8):1846-52. doi: 10.1016/j.tiv.2008.09.001. Epub 2008 Sep 9. Pubmed

6. Canalicular multispecific organic anion transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 1 Q92887 Details

References:

  1. https://www.pharmgkb.org/pathway/PA150642262#

Comments
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12