General Information of Drug (ID: DMRHGI9)

Drug Name
Cisplatin
Synonyms
Abiplatin; Biocisplatinum; Briplatin; Cismaplat; Cisplatine; Cisplatino; Cisplatinum; Cisplatyl; Citoplationo; Lederplatin; Neoplatin; Plastin; Platamine; Platidiam; Platinoxan; Randa; Cis-DDP; Cis-Diamminedichloroplatinum; Peyrone's chloride; Peyrone's salt; Cis-Dichlorodiammineplatinum(II); Cis-[PtCl2(NH3)2]; Cis-diamminedichloridoplatinum(II); Trans-diamminedichloridoplatinum(II); (SP-4-1)-diamminedichloridoplatinum; (SP-4-1)-diamminedichloroplatinum; (SP-4-2)-diamminedichloridoplatinum; (SP-4-2)-diamminedichloroplatinum; Cisplatin (Chemotherapy)
Indication
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Approved [1], [2]
Osteosarcoma 2B51 Phase 2 [3]
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski):
0
Molecular Weight 300.05
Topological Polar Surface Area Not Available
Rotatable Bond Count 0
Hydrogen Bond Donor Count 2
Hydrogen Bond Acceptor Count 2
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [4]
Elimination
2.3% of drug is excreted from urine in the unchanged form [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 30 minutes (platinum in plasma), and more than 5 days (complexes between albuminutes and the platinum) [5]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 4.74882 micromolar/kg/day [6]
Water Solubility
The ability of drug to dissolve in water is measured as 2.53 mg/mL [4]
Chemical Identifiers
Formula
Cl2H6N2Pt
IUPAC Name
azane;dichloroplatinum
Canonical SMILES
N.N.Cl[Pt]Cl
InChI
InChI=1S/2ClH.2H3N.Pt/h2*1H;2*1H3;/q;;;;+2/p-2
InChIKey
LXZZYRPGZAFOLE-UHFFFAOYSA-L
Cross-matching ID
PubChem CID
5702198
CAS Number
15663-27-1
DrugBank ID
DB00515
TTD ID
D0U5HU
VARIDT ID
DR00291
INTEDE ID
DR0332
ACDINA ID
D00950

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Modulator [7]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
High affinity copper uptake protein 1 (SLC31A1) DTP8L4F COPT1_HUMAN Substrate [8]
Copper-transporting ATPase 2 (ATP7B) DT206GF ATP7B_HUMAN Substrate [9]
Multidrug resistance-associated protein 6 (ABCC6) DT582KR MRP6_HUMAN Substrate [10]
Probable low affinity copper uptake protein 2 (SLC31A2) DT8Q56F COPT2_HUMAN Substrate [11]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [12]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [13]
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [14]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [15]
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [16]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [17]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Substrate [18]
Glutathione S-transferase alpha-1 (GSTA1) DE4ZHS1 GSTA1_HUMAN Substrate [19]
Quinone reductase 1 (NQO1) DENP5RY NQO1_HUMAN Substrate [20]
Glutathione S-transferase pi (GSTP1) DEK6079 GSTP1_HUMAN Substrate [21]
Metallothionein-1A (MT1A) DE5ME8A MT1A_HUMAN Substrate [22]
Myeloperoxidase (MPO) DEA3U9Y PERM_HUMAN Substrate [23]
Metallothionein-2A (MT2A) DEFKGT7 MT2_HUMAN Substrate [22]
Glutathione S-transferase mu-1 (GSTM1) DEYZEJA GSTM1_HUMAN Substrate [21]
Superoxide dismutase 1 (SOD1) DEUTDON SODC_HUMAN Substrate [20]
Glutathione S-transferase theta-1 (GSTT1) DE3PKUG GSTT1_HUMAN Substrate [21]
Glutathione S-transferase alpha-4 (GSTA4) DEH7XYP GSTA4_HUMAN Substrate [24]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Cisplatin (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Decreased renal excretion of Cisplatin caused by Remdesivir mediated nephrotoxicity. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [117]
Inotersen DMJ93CT Major Increased risk of nephrotoxicity by the combination of Cisplatin and Inotersen. Amyloidosis [5D00] [118]
Dronedarone DMA8FS5 Major Increased risk of ventricular arrhythmias by the combination of Cisplatin and Dronedarone. Angina pectoris [BA40] [119]
Roflumilast DMPGHY8 Moderate Additive immunosuppressive effects by the combination of Cisplatin and Roflumilast. Asthma [CA23] [118]
Ofloxacin DM0VQN3 Minor Decreased absorption of Cisplatin due to intestinal mucosa variation caused by Ofloxacin. Bacterial infection [1A00-1C4Z] [120]
Ciprofloxacin XR DM2NLS9 Minor Decreased absorption of Cisplatin due to intestinal mucosa variation caused by Ciprofloxacin XR. Bacterial infection [1A00-1C4Z] [120]
Trovafloxacin DM6AN32 Minor Decreased absorption of Cisplatin due to intestinal mucosa variation caused by Trovafloxacin. Bacterial infection [1A00-1C4Z] [120]
Sparfloxacin DMB4HCT Minor Decreased absorption of Cisplatin due to intestinal mucosa variation caused by Sparfloxacin. Bacterial infection [1A00-1C4Z] [120]
Gemifloxacin DMHT34O Minor Decreased absorption of Cisplatin due to intestinal mucosa variation caused by Gemifloxacin. Bacterial infection [1A00-1C4Z] [120]
Norfloxacin DMIZ6W2 Minor Decreased absorption of Cisplatin due to intestinal mucosa variation caused by Norfloxacin. Bacterial infection [1A00-1C4Z] [120]
ABT-492 DMJFD2I Minor Decreased absorption of Cisplatin due to intestinal mucosa variation caused by ABT-492. Bacterial infection [1A00-1C4Z] [120]
Rabeprazole DMMZXIW Moderate Increased risk of hypomagnesemia by the combination of Cisplatin and Rabeprazole. Bacterial infection [1A00-1C4Z] [121]
Levofloxacin DMS60RB Minor Decreased absorption of Cisplatin due to intestinal mucosa variation caused by Levofloxacin. Bacterial infection [1A00-1C4Z] [120]
Lomefloxacin DMVRH9C Minor Decreased absorption of Cisplatin due to intestinal mucosa variation caused by Lomefloxacin. Bacterial infection [1A00-1C4Z] [120]
Etidronic acid DM1XHYJ Moderate Increased risk of nephrotoxicity by the combination of Cisplatin and Etidronic acid. Bone paget disease [FB85] [122]
Iodipamide DMXIQYS Major Increased risk of nephrotoxicity by the combination of Cisplatin and Iodipamide. Cholelithiasis [DC11] [123]
Methoxyflurane DML0RAE Moderate Increased risk of nephrotoxicity by the combination of Cisplatin and Methoxyflurane. Corneal disease [9A76-9A78] [118]
Ethacrynic acid DM60QMR Moderate Increased risk of ototoxicity by the combination of Cisplatin and Ethacrynic acid. Essential hypertension [BA00] [124]
Amphotericin B DMTAJQE Moderate Increased risk of nephrotoxicity by the combination of Cisplatin and Amphotericin B. Fungal infection [1F29-1F2F] [117]
Dexlansoprazole DM1DBV5 Moderate Increased risk of hypomagnesemia by the combination of Cisplatin and Dexlansoprazole. Gastro-oesophageal reflux disease [DA22] [121]
Furosemide DMMQ8ZG Moderate Increased risk of ototoxicity by the combination of Cisplatin and Furosemide. Heart failure [BD10-BD1Z] [125]
Bumetanide DMRV7H0 Moderate Increased risk of ototoxicity by the combination of Cisplatin and Bumetanide. Heart failure [BD10-BD1Z] [125]
Brentuximab vedotin DMWLC57 Moderate Increased risk of peripheral neuropathy by the combination of Cisplatin and Brentuximab vedotin. Hodgkin lymphoma [2B30] [126]
Zalcitabine DMH7MUV Moderate Increased risk of peripheral neuropathy by the combination of Cisplatin and Zalcitabine. Human immunodeficiency virus disease [1C60-1C62] [127]
Teriflunomide DMQ2FKJ Major Additive immunosuppressive effects by the combination of Cisplatin and Teriflunomide. Hyper-lipoproteinaemia [5C80] [128]
Etelcalcetide DMHP9BL Major Increased risk of hypocalcemia by the combination of Cisplatin and Etelcalcetide. Hyper-parathyroidism [5A51] [118]
Diazoxide DML1538 Minor Increased risk of nephrotoxicity by the combination of Cisplatin and Diazoxide. Hypertension [BA00-BA04] [129]
Givosiran DM5PFIJ Moderate Increased risk of nephrotoxicity by the combination of Cisplatin and Givosiran. Inborn porphyrin/heme metabolism error [5C58] [117]
Balsalazide DMO091F Moderate Increased risk of nephrotoxicity by the combination of Cisplatin and Balsalazide. Indeterminate colitis [DD72] [130]
Methotrexate DM2TEOL Moderate Increased risk of nephrotoxicity by the combination of Cisplatin and Methotrexate. Leukaemia [2A60-2B33] [117]
Ibandronate DM0QZBN Moderate Increased risk of nephrotoxicity by the combination of Cisplatin and Ibandronate. Low bone mass disorder [FB83] [131]
Denosumab DMNI0KO Moderate Additive immunosuppressive effects by the combination of Cisplatin and Denosumab. Low bone mass disorder [FB83] [132]
Arsenic trioxide DM61TA4 Major Increased risk of ventricular arrhythmias by the combination of Cisplatin and Arsenic trioxide. Mature B-cell lymphoma [2A85] [133]
Clofarabine DMCVJ86 Moderate Increased risk of nephrotoxicity by the combination of Cisplatin and Clofarabine. Mature B-cell lymphoma [2A85] [134]
Exjade DMHPRWG Major Increased risk of nephrotoxicity by the combination of Cisplatin and Exjade. Mineral absorption/transport disorder [5C64] [135]
Thalidomide DM70BU5 Major Additive thrombogenic effects by the combination of Cisplatin and Thalidomide. Multiple myeloma [2A83] [136]
Tecfidera DM2OVDT Moderate Additive immunosuppressive effects by the combination of Cisplatin and Tecfidera. Multiple sclerosis [8A40] [137]
Siponimod DM2R86O Major Additive immunosuppressive effects by the combination of Cisplatin and Siponimod. Multiple sclerosis [8A40] [117]
Fingolimod DM5JVAN Major Additive immunosuppressive effects by the combination of Cisplatin and Fingolimod. Multiple sclerosis [8A40] [138]
Ocrelizumab DMEZ2KH Moderate Additive immunosuppressive effects by the combination of Cisplatin and Ocrelizumab. Multiple sclerosis [8A40] [139]
Ozanimod DMT6AM2 Major Additive immunosuppressive effects by the combination of Cisplatin and Ozanimod. Multiple sclerosis [8A40] [118]
Omacetaxine mepesuccinate DMPU2WX Moderate Additive myelosuppressive effects by the combination of Cisplatin and Omacetaxine mepesuccinate. Myeloproliferative neoplasm [2A20] [140]
Levomethadyl Acetate DM06HG5 Major Increased risk of ventricular arrhythmias by the combination of Cisplatin and Levomethadyl Acetate. Opioid use disorder [6C43] [141]
Esomeprazole DM7BN0X Moderate Increased risk of hypomagnesemia by the combination of Cisplatin and Esomeprazole. Peptic ulcer [DA61] [121]
Pemetrexed DMMX2E6 Moderate Decreased renal excretion of Cisplatin caused by Pemetrexed mediated nephrotoxicity. Pleural mesothelioma [2C26] [142]
Fluphenazine DMIT8LX Moderate Increased risk of ventricular arrhythmias by the combination of Cisplatin and Fluphenazine. Psychotic disorder [6A20-6A25] [117]
Everolimus DM8X2EH Major Increased risk of nephrotoxicity by the combination of Cisplatin and Everolimus. Renal cell carcinoma [2C90] [143]
Temsirolimus DMS104F Major Increased risk of nephrotoxicity by the combination of Cisplatin and Temsirolimus. Renal cell carcinoma [2C90] [143]
Gatifloxacin DMSL679 Minor Decreased absorption of Cisplatin due to intestinal mucosa variation caused by Gatifloxacin. Respiratory infection [CA07-CA4Z] [120]
Canakinumab DM8HLO5 Moderate Additive immunosuppressive effects by the combination of Cisplatin and Canakinumab. Rheumatoid arthritis [FA20] [144]
Rilonacept DMGLUQS Moderate Additive immunosuppressive effects by the combination of Cisplatin and Rilonacept. Rheumatoid arthritis [FA20] [144]
Golimumab DMHZV7X Major Additive immunosuppressive effects by the combination of Cisplatin and Golimumab. Rheumatoid arthritis [FA20] [145]
Sulfasalazine DMICA9H Moderate Increased risk of nephrotoxicity by the combination of Cisplatin and Sulfasalazine. Rheumatoid arthritis [FA20] [130]
Leflunomide DMR8ONJ Major Additive myelosuppressive effects by the combination of Cisplatin and Leflunomide. Rheumatoid arthritis [FA20] [128]
Thioridazine DM35M8J Moderate Increased risk of ventricular arrhythmias by the combination of Cisplatin and Thioridazine. Schizophrenia [6A20] [117]
Paliperidone DM7NPJS Moderate Increased risk of ventricular arrhythmias by the combination of Cisplatin and Paliperidone. Schizophrenia [6A20] [117]
Trifluoperazine DMKBYWI Moderate Increased risk of ventricular arrhythmias by the combination of Cisplatin and Trifluoperazine. Schizophrenia [6A20] [117]
Risperidone DMN6DXL Moderate Increased risk of ventricular arrhythmias by the combination of Cisplatin and Risperidone. Schizophrenia [6A20] [117]
Amisulpride DMSJVAM Moderate Increased risk of ventricular arrhythmias by the combination of Cisplatin and Amisulpride. Schizophrenia [6A20] [117]
Pimozide DMW83TP Major Increased risk of ventricular arrhythmias by the combination of Cisplatin and Pimozide. Schizophrenia [6A20] [146]
Anthrax vaccine DM9GSWY Moderate Antagonize the effect of Cisplatin when combined with Anthrax vaccine. Sepsis [1G40-1G41] [147]
Sirolimus DMGW1ID Major Increased risk of nephrotoxicity by the combination of Cisplatin and Sirolimus. Transplant rejection [NE84] [143]
Azathioprine DMMZSXQ Moderate Additive immunosuppressive effects by the combination of Cisplatin and Azathioprine. Transplant rejection [NE84] [117]
Tacrolimus DMZ7XNQ Major Increased risk of nephrotoxicity by the combination of Cisplatin and Tacrolimus. Transplant rejection [NE84] [143]
Olsalazine DMZW9HA Moderate Increased risk of nephrotoxicity by the combination of Cisplatin and Olsalazine. Ulcerative colitis [DD71] [130]
Cinoxacin DM4EWNS Minor Decreased absorption of Cisplatin due to intestinal mucosa variation caused by Cinoxacin. Urinary tract infection [GC08] [120]
Nalidixic acid DMRM0JV Minor Decreased absorption of Cisplatin due to intestinal mucosa variation caused by Nalidixic acid. Urinary tract infection [GC08] [120]
Amiodarone DMUTEX3 Major Increased risk of ventricular arrhythmias by the combination of Cisplatin and Amiodarone. Ventricular tachyarrhythmia [BC71] [148]
Ganciclovir DM1MBYQ Moderate Increased risk of nephrotoxicity by the combination of Cisplatin and Ganciclovir. Virus infection [1A24-1D9Z] [117]
Valaciclovir DMHKS94 Moderate Increased risk of nephrotoxicity by the combination of Cisplatin and Valaciclovir. Virus infection [1A24-1D9Z] [118]
Valganciclovir DMS2IUH Moderate Additive myelosuppressive effects by the combination of Cisplatin and Valganciclovir. Virus infection [1A24-1D9Z] [117]
⏷ Show the Full List of 71 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Mannitol E00103 6251 Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Sodium chloride E00077 5234 Diluent; Tonicity agent
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Cisplatin 10mg/vial injectable 10mg/vial Injectable Injection
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5343).
2 Using the zebrafish lateral line to screen for ototoxicity. J Assoc Res Otolaryngol. 2008 Jun;9(2):178-90.
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 BDDCS applied to over 900 drugs
5 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
7 Cisplatin and DNA repair in cancer chemotherapy.Trends Biochem Sci.1995 Oct;20(10):435-9.
8 Overcoming platinum drug resistance with copper-lowering agents. Anticancer Res. 2013 Oct;33(10):4157-61.
9 Effect of cisplatin on the transport activity of PII-type ATPases. Metallomics. 2017 Jul 19;9(7):960-968.
10 Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6). Cancer Res. 2002 Nov 1;62(21):6172-7.
11 Copper transporter 2 regulates endocytosis and controls tumor growth and sensitivity to cisplatin in vivo. Mol Pharmacol. 2011 Jan;79(1):157-66.
12 Lentivirus-mediated RNAi silencing targeting ABCC2 increasing the sensitivity of a human nasopharyngeal carcinoma cell line against cisplatin. J Transl Med. 2008 Oct 4;6:55.
13 Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are substrates for human organic cation transporters (SLC22A1-3 and multidrug and toxin extrusion family). J Pharmacol Exp Ther. 2006 Nov;319(2):879-86.
14 Hammerhead ribozyme against gamma-glutamylcysteine synthetase sensitizes human colonic cancer cells to cisplatin by down-regulating both the glutathione synthesis and the expression of multidrug resistance proteins. Cancer Gene Ther. 2001 Oct;8(10):803-14.
15 Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
16 Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2. Am J Pathol. 2005 Dec;167(6):1477-84.
17 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
18 Cytochrome P450 2E1 null mice provide novel protection against cisplatin-induced nephrotoxicity and apoptosis. Kidney Int. 2003 May;63(5):1687-96.
19 Role of glutathione S-transferase P1-1 in the cellular detoxification of cisplatin. Mol Cancer Ther. 2008 Oct;7(10):3247-55.
20 PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150642262)
21 Glutathione S-transferase genetic polymorphisms and individual sensitivity to the ototoxic effect of cisplatin. Anticancer Drugs. 2000 Sep;11(8):639-43.
22 Role of metallothionein in cisplatin sensitivity of germ-cell tumours. Int J Cancer. 2000 Mar 15;85(6):777-81.
23 Cisplatin reduces Brucella melitensis-infected cell number by inducing apoptosis, oxidant and pro-inflammatory cytokine production. Res Vet Sci. 2010 Apr;88(2):218-26.
24 GSTA4 mediates reduction of cisplatin ototoxicity in female mice. Nat Commun. 2019 Sep 12;10(1):4150.
25 Human glutathione transferase A3-3, a highly efficient catalyst of double-bond isomerization in the biosynthetic pathway of steroid hormones. J Biol Chem. 2001 Aug 31;276(35):33061-5.
26 Retinoid X receptor alpha regulates the expression of glutathione s-transferase genes and modulates acetaminophen-glutathione conjugation in mouse liver. Mol Pharmacol. 2005 Dec;68(6):1590-6.
27 Comparison of basal glutathione S-transferase activities and of the influence of phenobarbital, butylated hydroxy-anisole or 5,5'-diphenylhydantoin on enzyme activity in male rodents. Comp Biochem Physiol C. 1987;88(1):91-3.
28 Characterization and formation of the glutathione conjugate of clofibric acid. Drug Metab Dispos. 1995 Jan;23(1):119-23.
29 In vitro characterization of the human biotransformation and CYP reaction phenotype of ET-743 (Yondelis, Trabectidin), a novel marine anti-cancer drug. Invest New Drugs. 2006 Jan;24(1):3-14.
30 Glutathione S-transferase M1 polymorphism: a risk factor for hepatic venoocclusive disease in bone marrow transplantation. Blood. 2004 Sep 1;104(5):1574-7.
31 Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer. 2002 Feb 10;97(5):700-5.
32 Purification and biochemical properties of glutathione S-transferase from Lactuca sativa. J Biochem Mol Biol. 2005 Mar 31;38(2):232-7.
33 Combined glutathione-S-transferase M1 and T1 genetic polymorphism and tacrine hepatotoxicity. Clin Pharmacol Ther. 2000 Apr;67(4):432-7.
34 Metabolism of melphalan by rat liver microsomal glutathione S-transferase. Chem Biol Interact. 2005 Apr 15;152(2-3):101-6.
35 Chronic ethanol feeding and folate deficiency activate hepatic endoplasmic reticulum stress pathway in micropigs. Am J Physiol Gastrointest Liver Physiol. 2005 Jul;289(1):G54-63.
36 Genotoxicity of tamoxifen, tamoxifen epoxide and toremifene in human lymphoblastoid cells containing human cytochrome P450s. Carcinogenesis. 1994 Jan;15(1):5-9.
37 Acetaminophen induced acute liver failure via oxidative stress and JNK activation: protective role of taurine by the suppression of cytochrome P450 2E1. Free Radic Res. 2010 Mar;44(3):340-55.
38 A study on the metabolism of etoposide and possible interactions with antitumor or supporting agents by human liver microsomes. J Pharmacol Exp Ther. 1998 Sep;286(3):1294-300.
39 The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
40 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
41 Novel metabolic pathway of estrone and 17beta-estradiol catalyzed by cytochrome P-450. Drug Metab Dispos. 2000 Feb;28(2):110-2.
42 Inhibition of cytochrome P450 2E1 by propofol in human and porcine liver microsomes. Biochem Pharmacol. 2002 Oct 1;64(7):1151-6.
43 CYP2E1 and clinical features in alcoholics. Neuropsychobiology. 2003;47(2):86-9.
44 Effects of nicotine on cytochrome P450 2A6 and 2E1 activities. Br J Clin Pharmacol. 2010 Feb;69(2):152-9.
45 Reactions of glutathione with the catechol, the ortho-quinone and the semi-quinone free radical of etoposide. Consequences for DNA inactivation. Biochem Pharmacol. 1992 Apr 15;43(8):1761-8.
46 Busulfan conjugation by glutathione S-transferases alpha, mu, and pi. Drug Metab Dispos. 1996 Sep;24(9):1015-9.
47 The anti-cancer drug chlorambucil as a substrate for the human polymorphic enzyme glutathione transferase P1-1: kinetic properties and crystallographic characterisation of allelic variants. J Mol Biol. 2008 Jun 27;380(1):131-44.
48 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
49 Thiols as peroxidase substrates. Free Radic Biol Med. 1993 Feb;14(2):167-75.
50 Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: role of myeloperoxidase and arylamine free radicals. Chem Biol Interact. 2015 Sep 5;239:129-38.
51 Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52.
52 Beta-lapachone, a modulator of NAD metabolism, prevents health declines in aged mice. PLoS One. 2012;7(10):e47122.
53 Gene Therapy of the Central Nervous System. Charter 22 - Prodrug-Activation Gene Therapy. 2006, Pages 291-301
54 Dose-dependent response to 3-nitrobenzanthrone exposure in human urothelial cancer cells. Chem Res Toxicol. 2017 Oct 16;30(10):1855-1864.
55 PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA2040)
56 The role of bioreductive activation of doxorubicin in cytotoxic activity against leukaemia HL60-sensitive cell line and its multidrug-resistant sublines. Br J Cancer. 2005 Jul 11;93(1):89-97.
57 Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32.
58 Folate concentration dependent transport activity of the Multidrug Resistance Protein 1 (ABCC1). Biochem Pharmacol. 2004 Apr 15;67(8):1541-8.
59 Multidrug resistance-associated protein-1 functional activity in Calu-3 cells. J Pharmacol Exp Ther. 2001 Sep;298(3):1199-205.
60 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
61 ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P. Mol Pharmacol. 1999 May;55(5):921-8.
62 Structural determinants of substrate specificity differences between human multidrug resistance protein (MRP) 1 (ABCC1) and MRP3 (ABCC3). Drug Metab Dispos. 2008 Dec;36(12):2571-81.
63 Evaluation of transport of common antiepileptic drugs by human multidrug resistance-associated proteins (MRP1, 2 and 5) that are overexpressed in pharmacoresistant epilepsy. Neuropharmacology. 2010 Jun;58(7):1019-32.
64 Vinblastine and sulfinpyrazone export by the multidrug resistance protein MRP2 is associated with glutathione export. Br J Cancer. 2000 Aug;83(3):375-83.
65 Involvement of the drug transporters p glycoprotein and multidrug resistance-associated protein Mrp2 in telithromycin transport. Antimicrob Agents Chemother. 2006 Jan;50(1):80-7.
66 Dose-dependent disposition of methotrexate in Abcc2 and Abcc3 gene knockout murine models. Drug Metab Dispos. 2011 Nov;39(11):2155-61.
67 Mammalian multidrug-resistance proteins (MRPs). Essays Biochem. 2011 Sep 7;50(1):179-207.
68 Enhancing chemosensitivity in oral squamous cell carcinoma by lentivirus vector-mediated RNA interference targeting EGFR and MRP2. Oncol Lett. 2016 Sep;12(3):2107-2114.
69 Multidrug resistance associated protein 2 mediates transport of prostaglandin E2. Liver Int. 2006 Apr;26(3):362-8.
70 Effect of acetaminophen on expression and activity of rat liver multidrug resistance-associated protein 2 and P-glycoprotein. Biochem Pharmacol. 2004 Aug 15;68(4):791-8.
71 Small intestinal efflux mediated by MRP2 and BCRP shifts sulfasalazine intestinal permeability from high to low, enabling its colonic targeting. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G371-7.
72 Delineating the contribution of secretory transporters in the efflux of etoposide using Madin-Darby canine kidney (MDCK) cells overexpressing P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP1), and canalicular multispecific organic anion transporter (cMOAT). Drug Metab Dispos. 2002 Apr;30(4):457-63.
73 Multidrug Resistance-Associated Protein 2 (MRP2) Mediated Transport of Oxaliplatin-Derived Platinum in Membrane Vesicles. PLoS One. 2015 Jul 1;10(7):e0130727.
74 MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
75 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
76 Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
77 Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
78 Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
79 Efflux ratio cannot assess P-glycoprotein-mediated attenuation of absorptive transport: asymmetric effect of P-glycoprotein on absorptive and secretory transport across Caco-2 cell monolayers. Pharm Res. 2003 Aug;20(8):1200-9.
80 Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
81 Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
82 The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
83 Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
84 Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
85 The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
86 Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
87 Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
88 Characterization of 3-methoxy flavones for their interaction with ABCG2 as suggested by ATPase activity. Biochim Biophys Acta. 2014 Nov;1838(11):2929-38.
89 Are organic cation transporters capable of transporting prostaglandins? Naunyn Schmiedebergs Arch Pharmacol. 2005 Aug;372(2):125-30.
90 Relevance of copper transporter 1 and organic cation transporters 1-3 for oxaliplatin uptake and drug resistance in colorectal cancer cells. Metallomics. 2018 Mar 1;10(3):414-425.
91 Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 1997 Jul;16(7):871-81.
92 Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology. 2006 Jun;50(8):941-52.
93 Influx Transport of Cationic Drug at the Blood-Retinal Barrier: Impact on the Retinal Delivery of Neuroprotectants. Biol Pharm Bull. 2017;40(8):1139-1145.
94 The organic cation transporters (OCT1, OCT2, EMT) and the plasma membrane monoamine transporter (PMAT) show differential distribution and cyclic expression pattern in human endometrium and early pregnancy decidua. Mol Reprod Dev. 2007 Oct;74(10):1303-11.
95 Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet. 2005 Oct;20(5):379-86.
96 A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters. J Pharmacol Exp Ther. 2005 Oct;315(1):337-45.
97 Elevated systemic elimination of cimetidine in rats with acute biliary obstruction: the role of renal organic cation transporter OCT2. Drug Metab Pharmacokinet. 2010;25(4):328-34.
98 Pharmacologic markers and predictors of responses to imatinib therapy in patients with chronic myeloid leukemia. Leuk Lymphoma. 2008 Apr;49(4):639-42.
99 Organic cation transporters are determinants of oxaliplatin cytotoxicity. Cancer Res. 2006 Sep 1;66(17):8847-57.
100 Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett. 2006 Mar 8;234(1):4-33.
101 Upregulation of histone acetylation reverses organic anion transporter 2 repression and enhances 5-fluorouracil sensitivity in hepatocellular carcinoma
102 Comparison of type I and type II organic cation transport by organic cation transporters and organic anion-transporting polypeptides. J Pharmacol Exp Ther. 2001 Jul;298(1):110-5.
103 Organic cation transporters and their pharmacokinetic and pharmacodynamic consequences. Drug Metab Pharmacokinet. 2008;23(4):243-53.
104 The Transporter Classification Database (TCDB): recent advances. Nucleic Acids Res. 2016 Jan 4;44(D1):D372-9. (ID: 3.A.1.208.10)
105 Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs. Crit Rev Oncol Hematol. 2005 Jan;53(1):13-23.
106 Role of the copper transporter, CTR1, in platinum-induced ototoxicity. J Neurosci. 2010 Jul 14;30(28):9500-9.
107 Structures of oxaliplatin-oligonucleotide adducts from DNA.J Mass Spectrom.2012 Oct;47(10):1282-93.
108 31P NMR spectra of ethidium, quinacrine, and daunomycin complexes with poly(adenylic acid).poly(uridylic acid) RNA duplex and calf thymus DNA. Biochemistry. 1989 Apr 4;28(7):2804-12.
109 Pharmacokinetics and metabolism of ifosfamide in relation to DNA damage assessed by the COMET assay in children with cancer. Br J Cancer. 2005 May 9;92(9):1626-35.
110 O6-methylguanine-DNA methyltransferase activity and sensitivity to cyclophosphamide and cisplatin in human lung tumor xenografts. Int J Cancer. 1998 Sep 11;77(6):919-22.
111 Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer.Clin Cancer Res.2010 Oct 1;16(19):4899-905.
112 DNA intrastrand cross-link at the 5'-GA-3' sequence formed by busulfan and its role in the cytotoxic effect. Cancer Sci. 2004 May;95(5):454-8.
113 Brca2/Xrcc2 dependent HR, but not NHEJ, is required for protection against O(6)-methylguanine triggered apoptosis, DSBs and chromosomal aberrations... DNA Repair (Amst). 2009 Jan 1;8(1):72-86.
114 Structural studies of atom-specific anticancer drugs acting on DNA. Pharmacol Ther. 1999 Sep;83(3):181-215.
115 Predicting the myelotoxicity of chemotherapy: the use of pretreatment O6-methylguanine-DNA methyltransferase determination in peripheral blood mono... Melanoma Res. 2011 Dec;21(6):502-8.
116 Alkylation of DNA by melphalan in relation to immunoassay of melphalan-DNA adducts: characterization of mono-alkylated and cross-linked products fr... Chem Biol Interact. 1990;73(2-3):183-94.
117 Cerner Multum, Inc. "Australian Product Information.".
118 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
119 Product Information. Multaq (dronedarone). sanofi-aventis , Bridgewater, NJ.
120 Johnson EJ, MacGowan AP, Potter MN, et al "Reduced absorption of oral ciprofloxacin after chemotherapy for haematological malignancy." J Antimicrob Chemother 25 (1990): 837-42. [PMID: 2373666]
121 FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of proton pump inhibitor drugs (PPIs).".
122 Chang JT, Green L, Beitz J "Renal failure with the use of zoledronic acid." N Engl J Med 349 (2003): 1676-9 discussion 1676-9. [PMID: 14573746]
123 Wong GT, Lee EY, Irwin MG. Contrast induced nephropathy in vascular surgery.?Br J Anaesth. 2016;117 Suppl 2:ii63-ii73. [PMID: 27566809]
124 Product Information. Edecrin (ethacrynic acid). Merck &amp Co, Inc, West Point, PA.
125 Komune S, Snow JB "Potentiating effects of cisplatin and ethacrynic acid in ototoxicity." Arch Otolaryngol 107 (1981): 594-7. [PMID: 7197152]
126 Carrion C, Espinosa E, Herrero A, Garcia B "Possible vincristine-isoniazid interaction." Ann Pharmacother 29 (1995): 201. [PMID: 7756727]
127 Argov Z, Mastaglia FL "Drug-induced peripheral neuropathies." Br Med J 1 (1979): 663-6. [PMID: 219931]
128 Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
129 Markman M, Trump DL "Nephrotoxicity with cisplatin and antihypertensive medications." Ann Intern Med 96 (1982): 257. [PMID: 7199267]
130 Novis BH, Korzets Z, Chen P, Bernheim J "Nephrotic syndrome after treatment with 5-aminosalicylic acid." Br Med J (Clin Res Ed) 296 (1988): 1442. [PMID: 3132281]
131 Banerjee D, Asif A, Striker L, Preston RA, Bourgoignie JJ, Roth D "Short-term, high-dose pamidronate-induced acute tubular necrosis: The postulated mechanisms of bisphosphonate nephrotoxicity." Am J Kidney Dis 41 (2003): E18. [PMID: 12778436]
132 Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
133 Ohnishi K, Yoshida H, Shigeno K, et al. "Prolongation of the QT interval and ventricular tachycardia in patients treated with arsenic trioxide for acute promyelocytic leukemia." Ann Intern Med 133 (2000): 881-5. [PMID: 11103058]
134 Product Information. Clolar (clofarabine). sanofi-aventis, Bridgewater, NJ.
135 Product Information. Exjade (deferasirox). Novartis Pharmaceuticals, East Hanover, NJ.
136 Bennett CL, Nebeker JR, Samore MH, et al "The Research on Adverse Drug Events and Reports (RADAR) project." JAMA 293 (2005): 2131-40. [PMID: 15870417]
137 Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
138 Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
139 Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
140 Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
141 Cohen J "Long-term efficacy and safety of terazosin alone and in combination with other antihypertensive agents." Am Heart J 122 (1991): 919-25. [PMID: 1678923]
142 Product Information. Alimta (pemetrexed). Lilly, Eli and Company, Indianapolis, IN.
143 Product Information. Prograf (tacrolimus). Fujisawa, Deerfield, IL.
144 Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
145 Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
146 Product Information. Orap Tablets (pimozide). Gate Pharmaceuticals, Sellersville, PA.
147 CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]
148 Antonelli D, Atar S, Freedberg NA, Rosenfeld T "Torsade de pointes in patients on chronic amiodarone treatment: contributing factors and drug interactions." Isr Med Assoc J 7 (2005): 163-5. [PMID: 15792261]