QuickView for Cisplatin (compound)

Summary
General Info

PubChem

PubChem Compound 2767

Name:	Cisplatin
PubChem Compound ID:	2767
Description:	An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
Molecular formula:	Cl₂H₄N₂Pt
Molecular weight:	298.029 g/mol
Synonyms:	26035-31-4; Diamminedichloroplatinum; 15663-27-1; trans-Diamminedichloroplatinum (II); trans-Diamminedichloroplatinum; Platiblastin; Platinol; NSC241517; trans-Dichlorodiammine platinum; Dichlorodiammineplatinum (II). show more » 26035-31-4; Diamminedichloroplatinum; 15663-27-1; trans-Diamminedichloroplatinum (II); trans-Diamminedichloroplatinum; Platiblastin; Platinol; NSC241517; trans-Dichlorodiammine platinum; Dichlorodiammineplatinum (II); trans-Platinumdiammine dichloride; DDP; CACP; Platinum, diamminedichloro- (8CI 9CI); trans-Platinum(II) ammonium chloride; Platinum ammonium chloride; Platinum diamine dichloride; NCI-C55776; 14913-33-8; Platinum, diamminedichloro-, cis-; NSC131558; trans-Diaminedichloroplatinum; cis-Diaminedichloroplatinum; Platinum, diamminedichloro-, trans-; Replaced CAS registry number(s): 14283-03-5; NCGC00090759-01; trans-Dichlorodiammineplatinum (II); Cisplatin; cis-Dichlorodiamine platinum; Platinum(II), diamminedichloro-, trans-; CPDD; InChI=1/2ClH.2H2N.Pt/h21H;21H2;/q;;2*-1;+4/p-; Platinum ammine chloride; Platinum, diamminedichloro-, (SP-4-1)-; Platinum, diamminedichloro-, (SP-4-2)-; DDPt; NSC119875; cis Pt II show less «

DrugBank

Identification

Name:	Cisplatin
Name (isomeric):	DB00515
Drug Type:	small molecule
Description:	An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
Synonyms:	Diamminedichloroplatinum; Platinum Diamine Dichloride; Cis-Diamminedichloroplatinum; Cis-DDP; Trans-Platinumdiammine Dichloride; Trans-Diaminedichloroplatinum; Platinum Ammine Chloride; Trans-Dichlorodiammine Platinum; DDP; CPDD. show more » Diamminedichloroplatinum; Platinum Diamine Dichloride; Cis-Diamminedichloroplatinum; Cis-DDP; Trans-Platinumdiammine Dichloride; Trans-Diaminedichloroplatinum; Platinum Ammine Chloride; Trans-Dichlorodiammine Platinum; DDP; CPDD; CPDC; CACP; Cis-Diaminedichloroplatinum; DDPT; Platinum Ammonium Chloride; Trans-Diamminedichloroplatinum; Trans-DDP show less «
Brand:	Neoplatin, Plastin, Platamine, Platinol-AQ, Cis Pt II, Biocisplatinum, Cisplatine, Platiblastin, Briplatin, Cismaplat, Platidiam, Carboquone, Platinex, Abiplatin, Platinoxan, Cisplatyl, Randa, Lederplatin, Citoplationo, Platinol
Category:	Cross-Linking Reagents, Radiation-Sensitizing Agents, Antineoplastic Agents
CAS number:	15663-27-1

Pharmacology

Indication:	For the treatment of metastatic testicular tumors, metastatic ovarian tumors and advanced bladder cancer.
Pharmacology:	Cisplatin 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 atta... show more » Cisplatin 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. show less «
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 D... show more » 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. show less «
Protein binding:	Greater than 90%.
Route of elimination:	The parent compound, cisplatin, is excreted in the urine. Although small amounts of platinum are present in the bile and large intestine after administration of cisplatin, the fecal excretion of platinum appears to be insignificant.
Half Life:	20-30 minutes
Clearance:	15 - 16 L/h/m2 [After infusions of 100 mg/m2.]
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Echinacea should be used with caution, if at all, in patients receiving therapeutic immunosuppressants. Monitor for reduced efficacy of the immunosuppressant during concomitant use.

Drug interaction:

Natalizumab	Immunosuppressants such as cisplatin 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, and patients receiving chronic corticosteroids prior to natalizumab should be tapered off of steroids prior to starting natalizumab.
Trastuzumab	Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Furosemide	Increased ototoxicity
Roflumilast	Roflumilast may enhance the immunosuppressive effect of immunosuppressants such as cisplatin. The 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.
Amikacin	Increased risk of nephrotoxicity

Natalizumab	Immunosuppressants such as cisplatin 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, and patients receiving chronic corticosteroids prior to natalizumab should be tapered off of steroids prior to starting natalizumab.
Trastuzumab	Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Furosemide	Increased ototoxicity
Roflumilast	Roflumilast may enhance the immunosuppressive effect of immunosuppressants such as cisplatin. The 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.
Amikacin	Increased risk of nephrotoxicity
Pimecrolimus	Pimecrolimus may enhance the adverse/toxic effect of immunosuppressants such as cisplatin. Avoid use of pimecrolimus cream in patients receiving immunosuppressants.
Phenytoin	The antineoplasic agent decreases the effect of hydantoin
Docetaxel	Platinum derivatives such as cisplatin 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. Administer paclitaxel before cisplatin, when given as sequential infusions, to limit toxicity. Problems associated with other taxane/platinum combinations are possible, although unsubstantiated. Administering the taxane derivative before the platinum derivative seems prudent.
Netilmicin	Increased risk of nephrotoxicity
Gentamicin	Increased risk of nephrotoxicity
Cabazitaxel	Platinum derivatives such as cisplatin may enhance the myelosuppressive effect of taxane derivatives such as cabazitaxel. Administer taxane derivative before platinum derivative when given as sequential infusions to limit toxicity.Administer paclitaxel before cisplatin, when given as sequential infusions, to limit toxicity. Problems associated with other taxane/platinum combinations are possible, although unsubstantiated. Administering the taxane derivative before the platinum derivative seems prudent.
Ethacrynic acid	Increased ototoxicity
Fosphenytoin	The antineoplasic agent decreases the effect of hydantoin
Bumetanide	Increased ototoxicity
Tacrolimus	Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Cisplatin. Use caution during concomitant therapy.
Methotrexate	Cisplatin increases methotrexate toxicity
Topotecan	Administration of Topotecan after Cisplatin 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.
Tobramycin	Increased risk of nephrotoxicity
Leflunomide	Immunosuppressants such as cisplatin 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.
Paclitaxel	Cisplatin increases the effect and toxicity of paclitaxel

show less «

Targets

DNA

Transporters

Canalicular multispecific organic anion transporter 2

Multidrug resistance-associated protein 5

Canalicular multispecific organic anion transporter 1

Solute carrier family 22 member 2

High affinity copper uptake protein 1

Probable low affinity copper uptake protein 2

Multidrug resistance-associated protein 6

Multidrug resistance protein 1

Copper-transporting ATPase 2

Copper-transporting ATPase 1