Details of the Drug

General Information of Drug (ID: DMP6G8T)

Drug Name
Topotecan
Synonyms
Hycamptamine; Hycamptin; Hycamtamine; Topotecane; Topotecanum; Topotecan lactone; SKF 104864; SKF-S 104864; TOPOTECAN, HYCAMTIN; Topotecan (BAN); Topotecan [INN:BAN]; Topotecane [INN-French]; Topotecanum [INN-Latin]; Topotecan Monohydrochloride, (S)-Isomer; (4S)-10-[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; (S)-10-((Dimethylamino)methyl)-4-ethyl-4,9-dihydroxy-1H-pyrano(3',4':6,7)indolizino(1,2-b)quinoline-3,14(4H,12H)-dione; (S)-10-[(DIMETHYLAMINO)METHYL]-4-ETHYL-4,9-DIHYDROXY-1H-PYRANO[3',4':6,7]INOLIZINO[1,2-B]-QUINOLINE-3,14(4H,12H)-DIONE; (S)-10-[(Dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]-quinoline-3,14(4H,12H)-dione; (S)-10-[(Dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; 9-Dimethylaminomethyl-10-hydroxycamptothecin
Indication
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Approved [1], [2]
Solid tumour/cancer 2A00-2F9Z Approved [3]
Small-cell lung cancer 2C25.Y Phase 1 [4]
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 421.4
Topological Polar Surface Area (xlogp) 0.5
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 7
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [5]
Clearance
The drug present in the plasma can be removed from the body at the rate of 13 mL/min/kg [6]
Elimination
40% of drug is excreted from urine in the unchanged form [5]
Half-life
The concentration or amount of drug in body reduced by one-half in 2 - 3 hours [6]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 6.1572 micromolar/kg/day [7]
Unbound Fraction
The unbound fraction of drug in plasma is 0.65% [6]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.8 L/kg [6]
Water Solubility
The ability of drug to dissolve in water is measured as 1 mg/mL [5]
Chemical Identifiers
Formula
C23H23N3O5
IUPAC Name
(19S)-8-[(dimethylamino)methyl]-19-ethyl-7,19-dihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione
Canonical SMILES
CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=CC5=C(C=CC(=C5CN(C)C)O)N=C4C3=C2)O
InChI
InChI=1S/C23H23N3O5/c1-4-23(30)16-8-18-20-12(9-26(18)21(28)15(16)11-31-22(23)29)7-13-14(10-25(2)3)19(27)6-5-17(13)24-20/h5-8,27,30H,4,9-11H2,1-3H3/t23-/m0/s1
InChIKey
UCFGDBYHRUNTLO-QHCPKHFHSA-N
Cross-matching ID
PubChem CID
60700
ChEBI ID
CHEBI:63632
CAS Number
123948-87-8
DrugBank ID
DB01030
TTD ID
D02PMO
VARIDT ID
DR00044
ACDINA ID
D00690

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
DNA topoisomerase I (TOP1) TTGTQHC TOP1_HUMAN Modulator [8]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [9]
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [10]
Multidrug and toxin extrusion protein 2 (SLC47A2) DT3TX4H S47A2_HUMAN Substrate [11]
Multidrug and toxin extrusion protein 1 (SLC47A1) DTZGT0P S47A1_HUMAN Substrate [11]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [12]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [13]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Ovarian cancer
ICD Disease Classification 2C73
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
DNA topoisomerase I (TOP1) DTT TOP1 6.65E-01 0.2 0.39
Multidrug and toxin extrusion protein 1 (SLC47A1) DTP MATE1 1.37E-11 -4.84E-01 -6.68E-01
P-glycoprotein 1 (ABCB1) DTP P-GP 3.12E-33 -8.30E-01 -1.04E+00
Multidrug resistance-associated protein 1 (ABCC1) DTP MRP1 1.90E-30 1.76E-01 7.31E-01
Breast cancer resistance protein (ABCG2) DTP BCRP 3.87E-47 -1.28E+00 -1.63E+00
Multidrug resistance-associated protein 4 (ABCC4) DTP MRP4 1.26E-03 -4.35E-01 -5.28E-01
Multidrug and toxin extrusion protein 2 (SLC47A2) DTP MATE2 1.49E-18 1.67E-01 6.92E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Topotecan (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Arn-509 DMT81LZ Moderate Accelerated clearance of Topotecan due to the transporter induction by Arn-509. Acute myeloid leukaemia [2A60] [61]
Gilteritinib DMWQ4MZ Moderate Decreased clearance of Topotecan due to the transporter inhibition by Gilteritinib. Acute myeloid leukaemia [2A60] [62]
Roflumilast DMPGHY8 Moderate Additive immunosuppressive effects by the combination of Topotecan and Roflumilast. Asthma [CA23] [61]
Ofloxacin DM0VQN3 Minor Decreased absorption of Topotecan due to intestinal mucosa variation caused by Ofloxacin. Bacterial infection [1A00-1C4Z] [63]
Sparfloxacin DMB4HCT Minor Decreased absorption of Topotecan due to intestinal mucosa variation caused by Sparfloxacin. Bacterial infection [1A00-1C4Z] [63]
Gemifloxacin DMHT34O Minor Decreased absorption of Topotecan due to intestinal mucosa variation caused by Gemifloxacin. Bacterial infection [1A00-1C4Z] [63]
Norfloxacin DMIZ6W2 Minor Decreased absorption of Topotecan due to intestinal mucosa variation caused by Norfloxacin. Bacterial infection [1A00-1C4Z] [63]
ABT-492 DMJFD2I Minor Decreased absorption of Topotecan due to intestinal mucosa variation caused by ABT-492. Bacterial infection [1A00-1C4Z] [63]
Levofloxacin DMS60RB Minor Decreased absorption of Topotecan due to intestinal mucosa variation caused by Levofloxacin. Bacterial infection [1A00-1C4Z] [63]
Ag-221 DMS0ZBI Moderate Decreased clearance of Topotecan due to the transporter inhibition by Ag-221. BCR-ABL1-negative chronic myeloid leukaemia [2A41] [62]
Erdafitinib DMI782S Moderate Decreased clearance of Topotecan due to the transporter inhibition by Erdafitinib. Bladder cancer [2C94] [64]
Tucatinib DMBESUA Moderate Decreased clearance of Topotecan due to the transporter inhibition by Tucatinib. Breast cancer [2C60-2C6Y] [65]
PF-04449913 DMSB068 Moderate Decreased clearance of Topotecan due to the transporter inhibition by PF-04449913. Chronic myelomonocytic leukaemia [2A40] [61]
Fostemsavir DM50ILT Moderate Decreased clearance of Topotecan due to the transporter inhibition by Fostemsavir. Human immunodeficiency virus disease [1C60-1C62] [66]
Teriflunomide DMQ2FKJ Major Additive myelosuppressive effects by the combination of Topotecan and Teriflunomide. Hyper-lipoproteinaemia [5C80] [67]
BMS-201038 DMQTAGO Moderate Decreased clearance of Topotecan due to the transporter inhibition by BMS-201038. Hyper-lipoproteinaemia [5C80] [68]
Tolvaptan DMIWFRL Moderate Decreased clearance of Topotecan due to the transporter inhibition by Tolvaptan. Hypo-osmolality/hyponatraemia [5C72] [62]
Denosumab DMNI0KO Moderate Additive myelosuppressive effects by the combination of Topotecan and Denosumab. Low bone mass disorder [FB83] [69]
Capmatinib DMYCXKL Moderate Decreased clearance of Topotecan due to the transporter inhibition by Capmatinib. Lung cancer [2C25] [70]
Lasmiditan DMXLVDT Moderate Decreased clearance of Topotecan due to the transporter inhibition by Lasmiditan. Migraine [8A80] [71]
Thalidomide DM70BU5 Major Additive thrombogenic effects by the combination of Topotecan and Thalidomide. Multiple myeloma [2A83] [72]
Tecfidera DM2OVDT Moderate Additive immunosuppressive effects by the combination of Topotecan and Tecfidera. Multiple sclerosis [8A40] [73]
Siponimod DM2R86O Major Additive immunosuppressive effects by the combination of Topotecan and Siponimod. Multiple sclerosis [8A40] [62]
Fingolimod DM5JVAN Major Additive immunosuppressive effects by the combination of Topotecan and Fingolimod. Multiple sclerosis [8A40] [74]
Ozanimod DMT6AM2 Major Additive immunosuppressive effects by the combination of Topotecan and Ozanimod. Multiple sclerosis [8A40] [61]
Omacetaxine mepesuccinate DMPU2WX Moderate Additive immunosuppressive effects by the combination of Topotecan and Omacetaxine mepesuccinate. Myeloproliferative neoplasm [2A20] [75]
Rolapitant DM8XP26 Moderate Decreased clearance of Topotecan due to the transporter inhibition by Rolapitant. Nausea/vomiting [MD90] [76]
Lonafarnib DMGM2Z6 Moderate Decreased clearance of Topotecan due to the transporter inhibition by Lonafarnib. Premature ageing appearance [LD2B] [77]
Enzalutamide DMGL19D Moderate Accelerated clearance of Topotecan due to the transporter induction by Enzalutamide. Prostate cancer [2C82] [78]
Darolutamide DMV7YFT Moderate Decreased clearance of Topotecan due to the transporter inhibition by Darolutamide. Prostate cancer [2C82] [79]
Gatifloxacin DMSL679 Minor Decreased absorption of Topotecan due to intestinal mucosa variation caused by Gatifloxacin. Respiratory infection [CA07-CA4Z] [63]
Canakinumab DM8HLO5 Moderate Additive immunosuppressive effects by the combination of Topotecan and Canakinumab. Rheumatoid arthritis [FA20] [80]
Rilonacept DMGLUQS Moderate Additive immunosuppressive effects by the combination of Topotecan and Rilonacept. Rheumatoid arthritis [FA20] [80]
Golimumab DMHZV7X Major Additive immunosuppressive effects by the combination of Topotecan and Golimumab. Rheumatoid arthritis [FA20] [81]
Leflunomide DMR8ONJ Major Additive immunosuppressive effects by the combination of Topotecan and Leflunomide. Rheumatoid arthritis [FA20] [67]
Anthrax vaccine DM9GSWY Moderate Antagonize the effect of Topotecan when combined with Anthrax vaccine. Sepsis [1G40-1G41] [82]
Tedizolid DMG2SKR Moderate Decreased clearance of Topotecan due to the transporter inhibition by Tedizolid. Skin and skin-structure infection [1F28-1G0Z] [61]
Fostamatinib DM6AUHV Moderate Decreased clearance of Topotecan due to the transporter inhibition by Fostamatinib. Thrombocytopenia [3B64] [83]
Eltrombopag DMOGFIX Moderate Decreased clearance of Topotecan due to the transporter inhibition by Eltrombopag. Thrombocytopenia [3B64] [84]
Valganciclovir DMS2IUH Moderate Additive myelosuppressive effects by the combination of Topotecan and Valganciclovir. Virus infection [1A24-1D9Z] [62]
⏷ Show the Full List of 40 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
Glyceryl monostearate E00310 24699 Emollient; Emulsifying agent; Emulsion stabilizing agent; Solubilizing agent; Surfactant; Viscosity-controlling agent
Hydrochloric acid E00015 313 Acidulant
Mannitol E00103 6251 Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Eisenoxyd E00585 56841934 Colorant
Gelatin E00630 Not Available Other agent
Sodium hydroxide E00234 14798 Alkalizing agent
Tartaric acid E00029 875 Acidulant; Complexing agent; Flavoring agent
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Haematite red E00236 14833 Colorant
⏷ Show the Full List of 9 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Topotecan 0.25 mg capsule 0.25 mg Oral Capsule Oral
Topotecan 1 mg capsule 1 mg Oral Capsule Oral
Topotecan Hydrochloride eq 0.25mg base capsule eq 0.25mg base Capsule Oral
Topotecan Hydrochloride eq 4mg base/vial injectable eq 4mg base/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: 7101).
2 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
3 Plant-derived compounds in clinical trials. Drug Discov Today. 2008 Feb;13(3-4):161-71.
4 ClinicalTrials.gov (NCT00765973) Topotecan Liposomes Injection for Small Cell Lung Cancer (SCLC), Ovarian Cancer and Other Advanced Solid Tumors. U.S. National Institutes of Health.
5 BDDCS applied to over 900 drugs
6 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
7 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
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
9 Topotecan is a substrate for multidrug resistance associated protein 4. Curr Drug Metab. 2006 Jan;7(1):105-18.
10 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
11 Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71.
12 Differential inhibition of murine Bcrp1/Abcg2 and human BCRP/ABCG2 by the mycotoxin fumitremorgin C. Eur J Pharmacol. 2010 Oct 10;644(1-3):41-8.
13 Involvement of P-glycoprotein, multidrug resistance protein 2 and breast cancer resistance protein in the transport of belotecan and topotecan in Caco-2 and MDCKII cells. Pharm Res. 2008 Nov;25(11):2601-12.
14 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.
15 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.
16 Folate concentration dependent transport activity of the Multidrug Resistance Protein 1 (ABCC1). Biochem Pharmacol. 2004 Apr 15;67(8):1541-8.
17 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.
18 Multidrug resistance-associated protein-1 functional activity in Calu-3 cells. J Pharmacol Exp Ther. 2001 Sep;298(3):1199-205.
19 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.
20 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.
21 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.
22 Vinblastine and sulfinpyrazone export by the multidrug resistance protein MRP2 is associated with glutathione export. Br J Cancer. 2000 Aug;83(3):375-83.
23 MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
24 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.
25 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
26 Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
27 Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
28 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.
29 Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
30 Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
31 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.
32 Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
33 Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
34 Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
35 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.
36 Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
37 Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
38 Human multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter: functional characterization, interaction with OCT2 (SLC22A2), and single nucleotide polymorphisms. Am J Physiol Renal Physiol. 2010 Apr;298(4):F997-F1005.
39 Molecular mechanism of renal tubular secretion of the antimalarial drug chloroquine. Antimicrob Agents Chemother. 2011 Jul;55(7):3091-8.
40 Reduced renal clearance of a zwitterionic substrate cephalexin in MATE1-deficient mice. J Pharmacol Exp Ther. 2010 Aug;334(2):651-6.
41 Abemaciclib Inhibits Renal Tubular Secretion Without Changing Glomerular Filtration Rate. Clin Pharmacol Ther. 2019 May;105(5):1187-1195.
42 FDA Drug Development and Drug Interactions
43 Expression of Organic Anion Transporter 1 or 3 in Human Kidney Proximal Tubule Cells Reduces Cisplatin Sensitivity. Drug Metab Dispos. 2018 May;46(5):592-599.
44 Interaction of nonsteroidal anti-inflammatory drugs with multidrug resistance protein (MRP) 2/ABCC2- and MRP4/ABCC4-mediated methotrexate transport. J Pharmacol Exp Ther. 2007 Jan;320(1):229-35.
45 Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer Res. 2002 Jun 1;62(11):3144-50.
46 ATP-binding cassette C transporters in human pancreatic carcinoma cell lines. Upregulation in 5-fluorouracil-resistant cells. Pancreatology. 2009;9(1-2):136-44.
47 The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9.
48 Steroid and bile acid conjugates are substrates of human multidrug-resistance protein (MRP) 4 (ATP-binding cassette C4). Biochem J. 2003 Apr 15;371(Pt 2):361-7.
49 P-glycoprotein, but not multidrug resistance protein 4, plays a role in the systemic clearance of irinotecan and SN-38 in mice. Drug Metab Lett. 2010 Dec;4(4):195-201.
50 Polymorphisms in multidrug resistance-associated protein gene 4 is associated with outcome in childhood acute lymphoblastic leukemia. Blood. 2009 Aug 13;114(7):1383-6.
51 Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues. Biochem J. 2002 Feb 1;361(Pt 3):497-503.
52 Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I. Biochem J. 2002 Sep 1;366(Pt 2):653-61.
53 Impact of natural products on developing new anti-cancer agents. Chem Rev. 2009 Jul;109(7):3012-43.
54 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
55 Characterization of protein kinase chk1 essential for the cell cycle checkpoint after exposure of human head and neck carcinoma A253 cells to a novel topoisomerase I inhibitor BNP1350. Mol Pharmacol.2000 Mar;57(3):453-9.
56 Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer. 2006 Oct;6(10):789-802.
57 Phase I study of topoisomerase I inhibitor exatecan mesylate (DX-8951f) given as weekly 24-hour infusions three of every four weeks. Clin Cancer Res. 2001 Dec;7(12):3963-70.
58 Edotecarin: a novel topoisomerase I inhibitor. Clin Colorectal Cancer. 2005 May;5(1):27-36.
59 Rubitecan. Expert Opin Investig Drugs. 2006 Jan;15(1):71-9.
60 Nonclinical pharmacokinetics and activity of etirinotecan pegol (NKTR-102), a long-acting topoisomerase 1 inhibitor, in multiple cancer models. Cancer Chemother Pharmacol. 2014 Dec;74(6):1125-37.
61 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
62 Cerner Multum, Inc. "Australian Product Information.".
63 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]
64 Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
65 Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
66 Product Information. Rukobia (fostemsavir). ViiV Healthcare, Research Triangle Park, NC.
67 Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
68 Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
69 Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
70 Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
71 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
72 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]
73 Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
74 Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
75 Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
76 Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA.
77 Product Information. Zokinvy (lonafarnib). Eiger BioPharmaceuticals, Palo Alto, CA.
78 Benoist G, van Oort I, et al "Drug-drug interaction potential in men treated with enzalutamide: Mind the gap." Br J Clin Pharmacol 0 (2017): epub. [PMID: 28881501]
79 Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
80 Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
81 Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
82 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]
83 Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.
84 Allred AJ, Bowen CJ, Park JW, et al. "Eltrombopag increases plasma rosuvastatin exposure in healthy volunteers." Br J Clin Pharmacol 72 (2011): 321-9. [PMID: 21434975]