Carboplatin

Identification

Summary

Carboplatin is a alkylating agent used to treat advanced ovarian cancer.

Brand Names
Paraplatin
Generic Name
Carboplatin
DrugBank Accession Number
DB00958
Background

Carboplatin is an organoplatinum antineoplastic alkylating agent used in the treatment of advanced ovarian carcinoma.9 Early clinical studies of carboplatin were performed in 1982.7 Carboplatin was developed as an analog of cisplatin with reduced nephrotoxicity and vomiting.3,7

Carboplatin was granted FDA approval on 3 March 1989.8

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 371.254
Monoisotopic: 371.044481331
Chemical Formula
C6H12N2O4Pt
Synonyms
  • Carboplatin
  • Carboplatine
  • Carboplatino
  • CBDCA
  • cis-(1,1-cyclobutanedicarboxylato)diammineplatinum(II)
  • cis-diammine(1,1-cyclobutanedicarboxylato)platinum
  • cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II)
External IDs
  • NSC-241240

Pharmacology

Indication

Carboplatin is indicated in combination with an established combination of chemotherapeutic agents for the initial treatment of advanced ovarian carcinoma.9 Carboplatin is also indicated for the palliative treatment of ovarian carcinoma, recurrent after prior chemotherapy.9

Pharmacology
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Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Carboplatin is an organoplatinum antineoplastic alkylating agent used in the treatment of advanced ovarian carcinoma.9 Carboplatin has a long duration of action as it is given every 4 weeks, and a narrow therapeutic index.9 Patients should be counselled regarding bone marrow suppression and anemia.9

Mechanism of action

Carboplatin predominantly acts by attaching alkyl groups to the nucleotides, leading to the formation of monoadducts, and DNA fragmenting when repair enzymes attempt to correct the error.4,9 2% of carboplatin's activity comes from DNA cross-linking from a base on one strand to a base on another, preventing DNA strands from separating for synthesis or transcription.4,1 Finally, carboplatin can induce a number of different mutations.4

TargetActionsOrganism
ADNA
cross-linking/alkylation
Humans
Absorption

The Cmax and AUC of carboplatin increase proportionally with increasing doses.9 A 75 mg/m2 dose reaches a Cmax of 9.06 ± 0.74 µg/mL, with an AUC of 27.18 ± 11.28 h*µg/mL.3,9 A 450 mg/m2 dose reaches a Cmax of 55.39 ± 18.30 µg/mL, with an AUC of 224.41 ± 69.07 h*µg/mL.3,9

Volume of distribution

The apparent volume of distribution after a 30 minute intravenous infusion of 300-500 mg/m2 was 16 L.9

Protein binding

Carboplatin is not bound to plasma protein.3 However, the free platinum is 40% irreversibly bound to plasma proteins.2

Metabolism

Carboplatin is predominantly eliminated as the unchanged parent compound.4,5

Route of elimination

Carboplatin is 65% eliminated in the urine within 12 hours, and 71% eliminated within 24 hours.3,9 An additional 3-5% is eliminated in urine from 24 hours to 96 hours.3,9 Biliary elimination has not been determined.3,9 Carboplatin is predominantly eliminated as the unchanged parent compound.4,5

Half-life

The distribution half life of carboplatin is 1.1-2 hours, and the elimination half life was2.6-5.9 hours.9

Clearance

The total body clearance after a 30 minute intravenous infusion of 300-500 mg/m2 was 4.4 L/h.9

Adverse Effects
Adverseeffects
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Toxicity

Patients experiencing an overdose of carboplatin may present with pronounced neutropenia and hepatotoxicity.6,9 Treat patients with symptomatic and supportive measures, which may include delaying their next treatment.6

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirCarboplatin may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbataceptThe risk or severity of adverse effects can be increased when Carboplatin is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Carboplatin.
AceclofenacThe risk or severity of nephrotoxicity can be increased when Carboplatin is combined with Aceclofenac.
AcemetacinThe risk or severity of nephrotoxicity can be increased when Carboplatin is combined with Acemetacin.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Carboplatin.
AcetaminophenCarboplatin may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Carboplatin which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidThe risk or severity of nephrotoxicity can be increased when Acetylsalicylic acid is combined with Carboplatin.
AclidiniumCarboplatin may decrease the excretion rate of Aclidinium which could result in a higher serum level.
Interactions
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Food Interactions
  • Avoid echinacea. Co-administration may decrease effectiveness of immunosuppressants.

Products

Products2
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dosage, form, labeller, route of administration, and marketing period.
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International/Other Brands
Paraplatin-AQ
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Carboplatin InjectionLiquid10 mg / mLIntravenousTEVA Canada Limited1994-12-31Not applicableCanada flag
Carboplatin InjectionSolution10 mg / mLIntravenousOmega Laboratories Ltd2013-06-10Not applicableCanada flag
Carboplatin Injection BPSolution10 mg / mLIntravenousPfizer Canada Ulc1997-07-30Not applicableCanada flag
Carboplatin Injection BPSolution10 mg / mLIntravenousAccord Healthcare Inc2015-03-11Not applicableCanada flag
Carboplatin Injection Liq 10mg/mlLiquid10 mg / mLIntravenousDavid Bull Laboratories (Pty) Ltd.1992-12-311998-08-13Canada flag
Carboplatin Injection, BPSolution10 mg / mLIntravenousStrides Pharma Canada IncNot applicableNot applicableCanada flag
ParaplatinInjection, powder, lyophilized, for solution150 mg/15mLIntravenousE.R. Squibb & Sons, L.L.C.2008-01-012009-05-14US flag
ParaplatinInjection, solution10 mg/1mLIntravenousE.R. Squibb & Sons, L.L.C.2007-01-012008-09-30US flag
ParaplatinInjection, powder, lyophilized, for solution50 mg/5mLIntravenousE.R. Squibb & Sons, L.L.C.2008-01-012009-03-14US flag
ParaplatinInjection, solution10 mg/1mLIntravenousE.R. Squibb & Sons, L.L.C.2007-01-012008-06-30US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CarboplatinInjection, solution50 mg/5mLIntravenousAuroMedics Pharma LLC2016-09-29Not applicableUS flag
CarboplatinInjection, powder, lyophilized, for solution10 mg/1mLIntravenousBedford Pharmaceuticals2006-01-172011-02-28US flag
CarboplatinInjection10 mg/1mLIntravenousSun Pharmaceutical Industries, Inc.2008-09-192016-06-30US flag
CarboplatinInjection, solution10 mg/1mLIntravenousSun Pharma Global Inc.2008-09-192014-06-27US flag
CarboplatinSolution150 mg/5mLIntravenousSanja Pharmaceuticals Company2016-09-29Not applicableUS flag
CarboplatinInjection, solution50 mg/5mLIntravenousCipla USA Inc.2007-01-18Not applicableUS flag
CARBOplatinInjection, solution10 mg/1mLIntravenousTeva Parenteral Medicines, Inc.2006-05-04Not applicableUS flag
CarboplatinInjection, solution10 mg/1mLIntravenousAlvogen Inc.2018-02-012019-09-01US flag
CarboplatinInjection, solution10 mg/1mLIntravenousGland Pharma Limited2017-02-20Not applicableUS flag
CarboplatinInjection, powder, lyophilized, for solution450 mg/45mLIntravenousPliva, Inc.2009-10-152010-01-31US flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
CARBOPLATIN DBL 450 MG/45 MLCarboplatin (450 mg/45ml)Injection, solutionIntravenousORNA İLAÇ TEKSTİL KİMYEVİ MAD. SAN. VE DIŞ TİC. LTD. ŞTİ.2020-08-14Not applicableTurkey flag
CARBOPLATIN DBL ENJ. SOL. 150 MG/15 ML FLAKON, 1 ADETCarboplatin (150 mg/15ml)Injection, solutionIntravenousORNA İLAÇ TEKSTİL KİMYEVİ MAD. SAN. VE DIŞ TİC. LTD. ŞTİ.2020-08-14Not applicableTurkey flag
CARBOPLATIN DBL ENJ. SOL. 50 MG/5 ML FLAKON, 1 ADETCarboplatin (50 mg/5ml)Injection, solutionIntravenousORNA İLAÇ TEKSTİL KİMYEVİ MAD. SAN. VE DIŞ TİC. LTD. ŞTİ.2020-08-14Not applicableTurkey flag

Categories

ATC Codes
L01XA02 — Carboplatin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as dicarboxylic acids and derivatives. These are organic compounds containing exactly two carboxylic acid groups.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Dicarboxylic acids and derivatives
Direct Parent
Dicarboxylic acids and derivatives
Alternative Parents
Carboxylic acid salts / Oxacyclic compounds / Organic transition metal salts / Metalloheterocyclic compounds / Organic oxides / Organic nitrogen compounds / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Aliphatic heteropolycyclic compound / Carbonyl group / Carboxylic acid salt / Dicarboxylic acid or derivatives / Hydrocarbon derivative / Metalloheterocycle / Organic metal salt / Organic nitrogen compound / Organic oxide / Organic oxygen compound
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
platinum coordination entity (CHEBI:31355)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
BG3F62OND5
CAS number
41575-94-4
InChI Key
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
IUPAC Name
7,7-diamino-6,8-dioxa-7-platinaspiro[3.5]nonane-5,9-dione
SMILES
[H][N]([H])([H])[Pt]1(OC(=O)C2(CCC2)C(=O)O1)[N]([H])([H])[H]

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 References
  1. 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. [Article]
  2. Sooriyaarachchi M, Narendran A, Gailer J: Comparative hydrolysis and plasma protein binding of cis-platin and carboplatin in human plasma in vitro. Metallomics. 2011 Jan;3(1):49-55. doi: 10.1039/c0mt00058b. Epub 2010 Dec 6. [Article]
  3. Oguri S, Sakakibara T, Mase H, Shimizu T, Ishikawa K, Kimura K, Smyth RD: Clinical pharmacokinetics of carboplatin. J Clin Pharmacol. 1988 Mar;28(3):208-15. doi: 10.1002/j.1552-4604.1988.tb03134.x. [Article]
  4. Povirk LF, Shuker DE: DNA damage and mutagenesis induced by nitrogen mustards. Mutat Res. 1994 Dec;318(3):205-26. doi: 10.1016/0165-1110(94)90015-9. [Article]
  5. Reece PA, Bishop JF, Olver IN, Stafford I, Hillcoat BL, Morstyn G: Pharmacokinetics of unchanged carboplatin (CBDCA) in patients with small cell lung carcinoma. Cancer Chemother Pharmacol. 1987;19(4):326-30. doi: 10.1007/BF00261482. [Article]
  6. Diaz CM, Fenix-Caballero SF, Palomo-Palomo C, Gandara-Ladronde Guevera MJ, Alegre-DelRey EJ, Blanco-Castano MA, Lopez-Vallejo JF, Diaz-Navarro J, Borrero-Rubio JM, Rios-Sanchez E: GM-006 Compliance with FDA recommendations about overdosing with carboplatin European Journal of Hospital Pharmacy: Science and Practice. 2014 Feb 24;21(Suppl 1):A116. [Article]
  7. Calvert AH, Harland SJ, Newell DR, Siddik ZH, Jones AC, McElwain TJ, Raju S, Wiltshaw E, Smith IE, Baker JM, Peckham MJ, Harrap KR: Early clinical studies with cis-diammine-1,1-cyclobutane dicarboxylate platinum II. Cancer Chemother Pharmacol. 1982;9(3):140-7. doi: 10.1007/BF00257742. [Article]
  8. FDA Approved Drug Products: Paraplatin (Carboplatin) Intravenous Injection (Discontinued) [Link]
  9. Dailymed: Carboplatin Intravenous Injection [Link]
Human Metabolome Database
HMDB0015093
KEGG Drug
D01363
PubChem Compound
38904
PubChem Substance
46507170
ChemSpider
8514637
RxNav
40048
ChEBI
31355
ChEMBL
CHEMBL1351
Therapeutic Targets Database
DAP000535
PharmGKB
PA448803
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Carboplatin
FDA label
Download (1.26 MB)
MSDS
Download (73.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentOvarian Cancer1
4CompletedTreatmentAdenocarcinomas / Carcinoma / Carcinoma, Large Cell / Neoplasms, Lung / Non-Small Cell Lung Carcinoma (NSCLC) / Squamous Cell Carcinoma (SCC)1
4CompletedTreatmentBreast Cancer1
4CompletedTreatmentCarcinoma, Large Cell / Neuroendocrine Tumours (NETs)1
4CompletedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)3
4CompletedTreatmentRetinoblastoma1
4Not Yet RecruitingTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
4RecruitingTreatmentBreast Cancer1
4RecruitingTreatmentCentral Nervous System Embryonal Tumors / Medulloblastomas1
4RecruitingTreatmentExtensive-stage Small Cell Lung Cancer (SCLC)1

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
  • APP Pharmaceuticals
  • Baxter International Inc.
  • Bedford Labs
  • Bell-More Laboratories Inc.
  • Ben Venue Laboratories Inc.
  • Bristol-Myers Squibb Co.
  • Cipla Ltd.
  • Ebewe Pharma
  • Fresenius Kabi AB
  • Generamedix Inc.
  • Hospira Inc.
  • Intas Pharmaceuticals Ltd.
  • Mead Johnson and Co.
  • Otn Generics Inc.
  • Pharmachemie BV
  • Pliva Inc.
  • Spectrum Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • Watson Pharmaceuticals
Dosage Forms
FormRouteStrength
InjectionParenteral50 mg
Injection, powder, lyophilized, for solutionIntravenous150 mg
InjectionIntravenous
Injection, solution10 mg/1ml
Injection
InjectionIntravenous10 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous10 mg/1mL
Injection, solutionIntravenous150 mg/15mL
Injection, solutionIntravenous450 mg/45mL
Injection, solutionIntravenous50 mg/5mL
Injection, solutionIntravenous600 mg/60mL
SolutionIntravenous150 mg/5mL
SolutionIntravenous450 mg/5mL
SolutionIntravenous50 mg/5mL
Injection, solution, concentrateIntravenous
Injection, solution, concentrateParenteral
LiquidIntravenous10 mg / mL
InjectionIntravenous10 mg
SolutionIntravenous10 mg / mL
SolutionIntravenous
SolutionIntravenous10 mg
Injection, powder, lyophilized, for solutionParenteral150 mg
SolutionParenteral150 mg
Solution, concentrateIntravenous150 mg
Injection, powder, lyophilized, for solutionIntravenous450 mg
Injection, powder, lyophilized, for solutionParenteral450 mg
SuspensionParenteral450 mg
Solution, concentrateIntravenous50 mg
Injection, solution, concentrateIntravenous; Parenteral10 MG/ML
Injection, powder, for solutionIntravenous
Injection, solution
Injection, powder, lyophilized, for solutionParenteral50 mg
Injection, solutionParenteral150 MG/15ML
Injection, solutionParenteral450 MG/45ML
Injection, solutionParenteral50 MG/5ML
Injection, solutionIntravenous; Parenteral
Injection, solution, concentrateIntravenous10 mg/ml
Injection, solution, concentrateIntravenous600 mg
InjectionIntravenous50 mg/5ml
InjectionIntravenous450 mg
InjectionIntravenous10 mg/ml
SolutionIntravenous10.00 mg/ml
Injection, solutionIntravenous10 mg/ml
SolutionIntravenous50 mg
SolutionIntravenous450 mg
SolutionIntravenous150 mg
Injection, powder, lyophilized, for solutionIntravenous150 mg/15mL
Injection, powder, lyophilized, for solutionIntravenous450 mg/45mL
Injection, powder, lyophilized, for solutionIntravenous50 mg/5mL
Injection, solutionIntravenous
Injection, solutionIntravenous10 mg/1mL
Powder, for solutionIntravenous150 mg / vial
SolutionParenteral10 mg
Solution10 mg/1ml
Prices
Unit descriptionCostUnit
Paraplatin 450 mg vial1474.46USD vial
Paraplatin 150 mg vial491.48USD vial
Carboplatin 150 mg vial255.31USD vial
Paraplatin 50 mg vial163.84USD vial
Carboplatin 450 mg vial156.25USD vial
Carboplatin 50 mg vial85.1USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility14 mg/mLFDA Label
Predicted Properties
PropertyValueSource
Water Solubility79.8 mg/mLALOGPS
logP0.14ALOGPS
logS-0.67ALOGPS
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area107.88 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity60.04 m3·mol-1ChemAxon
Polarizability18.27 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.6183
Blood Brain Barrier+0.8295
Caco-2 permeable-0.584
P-glycoprotein substrateNon-substrate0.6375
P-glycoprotein inhibitor INon-inhibitor0.9489
P-glycoprotein inhibitor IINon-inhibitor0.9968
Renal organic cation transporterNon-inhibitor0.9239
CYP450 2C9 substrateNon-substrate0.8745
CYP450 2D6 substrateNon-substrate0.8276
CYP450 3A4 substrateNon-substrate0.703
CYP450 1A2 substrateNon-inhibitor0.8142
CYP450 2C9 inhibitorNon-inhibitor0.854
CYP450 2D6 inhibitorNon-inhibitor0.9168
CYP450 2C19 inhibitorNon-inhibitor0.8607
CYP450 3A4 inhibitorNon-inhibitor0.6995
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9896
Ames testNon AMES toxic0.746
CarcinogenicityNon-carcinogens0.8906
BiodegradationReady biodegradable0.8235
Rat acute toxicity2.3469 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9596
hERG inhibition (predictor II)Non-inhibitor0.9767
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Drugtargets2
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Kind
Nucleotide
Organism
Humans
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.
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. [Article]
  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. [Article]
  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 Nov 9;373(5):1123-40. Epub 2007 Aug 23. [Article]
  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. [Article]
  5. Dailymed: Carboplatin Intravenous Injection [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Xanthine oxidase activity
Specific Function
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Ha...
Gene Name
XDH
Uniprot ID
P47989
Uniprot Name
Xanthine dehydrogenase/oxidase
Molecular Weight
146422.99 Da
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. [Article]
  2. Husain K, Whitworth C, Rybak LP: Time response of carboplatin-induced nephrotoxicity in rats. Pharmacol Res. 2004 Sep;50(3):291-300. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Peroxidase activity
Specific Function
Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production o...
Gene Name
MPO
Uniprot ID
P05164
Uniprot Name
Myeloperoxidase
Molecular Weight
83867.71 Da
References
  1. PharmGKB: Platinum Pathway, Pharmacokinetics/Pharmacodynamics [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glutathione transferase activity
Specific Function
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Acts on 1,2-epoxy-3-(4-nitrophenoxy)propane, phenethylisothiocyanate 4-nitrobenzyl chlorid...
Gene Name
GSTT1
Uniprot ID
P30711
Uniprot Name
Glutathione S-transferase theta-1
Molecular Weight
27334.755 Da
References
  1. PharmGKB: Platinum Pathway, Pharmacokinetics/Pharmacodynamics [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Zinc ion binding
Specific Function
Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.
Gene Name
MT1A
Uniprot ID
P04731
Uniprot Name
Metallothionein-1A
Molecular Weight
6120.19 Da
References
  1. PharmGKB: Platinum Pathway, Pharmacokinetics/Pharmacodynamics [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Zinc ion binding
Specific Function
Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.
Gene Name
MT2A
Uniprot ID
P02795
Uniprot Name
Metallothionein-2
Molecular Weight
6042.05 Da
References
  1. PharmGKB: Platinum Pathway, Pharmacokinetics/Pharmacodynamics [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
Gene Name
SOD1
Uniprot ID
P00441
Uniprot Name
Superoxide dismutase [Cu-Zn]
Molecular Weight
15935.685 Da
References
  1. Husain K, Scott B, Whitworth C, Rybak LP: Time response of carboplatin-induced hearing loss in rat. Hear Res. 2004 May;191(1-2):110-8. doi: 10.1016/j.heares.2004.01.011. [Article]
  2. Husain K, Whitworth C, Somani SM, Rybak LP: Partial protection by lipoic acid against carboplantin-induced ototoxicity in rats. Biomed Environ Sci. 2005 Jun;18(3):198-206. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
S-nitrosoglutathione binding
Specific Function
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.
Gene Name
GSTP1
Uniprot ID
P09211
Uniprot Name
Glutathione S-transferase P
Molecular Weight
23355.625 Da
References
  1. PharmGKB: Platinum Pathway, Pharmacokinetics/Pharmacodynamics [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
Gene Name
GSTM1
Uniprot ID
P09488
Uniprot Name
Glutathione S-transferase Mu 1
Molecular Weight
25711.555 Da
References
  1. PharmGKB: Platinum Pathway, Pharmacokinetics/Pharmacodynamics [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Superoxide dismutase activity
Specific Function
The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vit...
Gene Name
NQO1
Uniprot ID
P15559
Uniprot Name
NAD(P)H dehydrogenase [quinone] 1
Molecular Weight
30867.405 Da
References
  1. PharmGKB: Platinum Pathway, Pharmacokinetics/Pharmacodynamics [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Copper uptake transmembrane transporter activity
Specific Function
High-affinity, saturable copper transporter involved in dietary copper uptake.
Gene Name
SLC31A1
Uniprot ID
O15431
Uniprot Name
High affinity copper uptake protein 1
Molecular Weight
21090.545 Da
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. doi: 10.1124/mol.109.063172. Epub 2010 Feb 16. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Copper ion transmembrane transporter activity
Specific Function
Involved in low-affinity copper uptake.
Gene Name
SLC31A2
Uniprot ID
O15432
Uniprot Name
Probable low affinity copper uptake protein 2
Molecular Weight
15681.29 Da
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. doi: 10.1158/1078-0432.CCR-09-0311. Epub 2009 Jun 9. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Superoxide dismutase copper chaperone activity
Specific Function
May supply copper to copper-requiring proteins within the secretory pathway, when localized in the trans-Golgi network. Under conditions of elevated extracellular copper, it relocalized to the plas...
Gene Name
ATP7A
Uniprot ID
Q04656
Uniprot Name
Copper-transporting ATPase 1
Molecular Weight
163372.275 Da
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. [Article]
  2. Harrach S, Ciarimboli G: Role of transporters in the distribution of platinum-based drugs. Front Pharmacol. 2015 Apr 24;6:85. doi: 10.3389/fphar.2015.00085. eCollection 2015. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Copper-exporting atpase activity
Specific Function
Involved in the export of copper out of the cells, such as the efflux of hepatic copper into the bile.
Gene Name
ATP7B
Uniprot ID
P35670
Uniprot Name
Copper-transporting ATPase 2
Molecular Weight
157261.34 Da
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Oguri T, Fujiwara Y, Isobe T, Katoh O, Watanabe H, Yamakido M: Expression of gamma-glutamylcysteine synthetase (gamma-GCS) and multidrug resistance-associated protein (MRP), but not human canalicular multispecific organic anion transporter (cMOAT), genes correlates with exposure of human lung cancers to platinum drugs. Br J Cancer. 1998 Apr;77(7):1089-96. doi: 10.1038/bjc.1998.181. [Article]
  2. Hu S, Leblanc AF, Gibson AA, Hong KW, Kim JY, Janke LJ, Li L, Vasilyeva A, Finkelstein DB, Sprowl JA, Sweet DH, Schlatter E, Ciarimboli G, Schellens J, Baker SD, Pabla N, Sparreboom A: Identification of OAT1/OAT3 as Contributors to Cisplatin Toxicity. Clin Transl Sci. 2017 Sep;10(5):412-420. doi: 10.1111/cts.12480. Epub 2017 Jul 8. [Article]

Drug created on June 13, 2005 13:24 / Updated on October 26, 2021 21:40