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Identification
NameIrinotecan
Accession NumberDB00762  (APRD00579)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. It is a derivative of camptothecin that inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex, and causes double-strand DNA breakage and cell death. It is a derivative of camptothecin.

Structure
Thumb
Synonyms
SynonymLanguageCode
BiotecanNot AvailableNot Available
Camptothecin-11Not AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Camptosarinjection, solution20 mg/mLintravenousPharmacia and Upjohn Company1996-06-14Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Camptosarinjection, solution20 mg/mLintravenousPharmacia and Upjohn Company1996-06-14Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Irinotecan Hydrochlorideinjection20 mg/mLintravenousWest ward Pharmaceutical Corp2010-12-20Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Irinotecan Hydrochlorideinjection20 mg/mLintravenousWest ward Pharmaceutical Corp2010-12-20Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Irinotecan Hydrochlorideinjection, solution40 mg/2mLintravenousTeva Parenteral Medicines, Inc.2008-02-28Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Irinotecan Hydrochlorideinjection, solution100 mg/5mLintravenousTeva Parenteral Medicines, Inc.2008-02-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Irinotecan Hydrochlorideinjection20 mg/mLintravenousHeritage Pharmaceuticals Inc.2012-06-20Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Irinotecan Hydrochlorideinjection, solution20 mg/mLintravenousSagent Pharmaceuticals2012-04-20Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Irinotecan Hydrochlorideinjection, solution20 mg/mLintravenousSagent Pharmaceuticals2014-08-15Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Irinotecan Hydrochlorideinjection, solution20 mg/mLintravenousActavis Pharma, Inc.2015-01-05Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Irinotecan Hydrochlorideinjection40 mg/2mLintravenousSun Pharma Global FZE2008-04-21Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Irinotecan Hydrochlorideinjection100 mg/5mLintravenousSun Pharma Global FZE2008-04-21Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Irinotecan Hydrochlorideinjection20 mg/mLintravenousCipla Limited2008-02-20Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Irinotecan Hydrochlorideinjection20 mg/mLintravenousAreva Pharmaceuticals,Inc.2012-07-16Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Irinotecan Hydrochlorideinjection, solution20 mg/mLintravenousHospira Worldwide, Inc.2008-02-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Irinotecan Hydrochlorideinjection20 mg/mLintravenousAPP Pharmaceuticals, LLC2009-04-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Irinotecan Hydrochlorideinjection, solution20 mg/mLintravenousSandoz Inc2009-11-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Irinotecansolution20 mgintravenousPfizer Canada IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Over the Counter ProductsNot Available
International Brands
NameCompany
CamptoYakultHonsha Co. Ltd.
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Irinotecan Hydrochloride
Thumb
  • InChI Key: GURKHSYORGJETM-WAQYZQTGSA-N
  • Monoisotopic Mass: 622.255812707
  • Average Mass: 623.139
DBSALT000103
Categories
CAS number100286-90-6
WeightAverage: 586.678
Monoisotopic: 586.279134968
Chemical FormulaC33H38N4O6
InChI KeyUWKQSNNFCGGAFS-XIFFEERXSA-N
InChI
InChI=1S/C33H38N4O6/c1-3-22-23-16-21(43-32(40)36-14-10-20(11-15-36)35-12-6-5-7-13-35)8-9-27(23)34-29-24(22)18-37-28(29)17-26-25(30(37)38)19-42-31(39)33(26,41)4-2/h8-9,16-17,20,41H,3-7,10-15,18-19H2,1-2H3/t33-/m0/s1
IUPAC Name
(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-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)-heptaen-7-yl 4-(piperidin-1-yl)piperidine-1-carboxylate
SMILES
CCC1=C2CN3C(=CC4=C(COC(=O)[C@]4(O)CC)C3=O)C2=NC2=C1C=C(OC(=O)N1CCC(CC1)N1CCCCC1)C=C2
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as camptothecins. These are heterocyclic compounds comprising a planar pentacyclic ring structure, that includes a pyrrolo[3,4-beta]-quinoline moiety (rings A, B and C), conjugated pyridone moiety (ring D) and one chiral center at position 20 within the alpha-hydroxy lactone ring with (S) configuration (the E-ring).
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassCamptothecins
Sub ClassNot Available
Direct ParentCamptothecins
Alternative Parents
Substituents
  • Camptothecin
  • Hydroxyquinoline
  • Quinoline
  • Pyranopyridine
  • Piperidinecarboxylic acid
  • Pyridinone
  • 4-aminopiperidine
  • Benzenoid
  • Pyridine
  • Piperidine
  • Dicarboxylic acid or derivatives
  • Heteroaromatic compound
  • Tertiary alcohol
  • Tertiary aliphatic amine
  • Tertiary amine
  • Lactone
  • Lactam
  • Carboxylic acid ester
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of metastatic colorectal cancer (first-line therapy when administered with 5-fluorouracil and leucovorin). Also used in combination with cisplatin for the treatment of extensive small cell lung cancer. Irinotecan is currently under investigation for the treatment of metastatic or recurrent cervical cancer.
PharmacodynamicsIrinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. Irinotecan is a semisynthetic derivative of camptothecin. Camptothecins interact specifically with topoisomerase I, an enzyme in the cell nucleus that regulates DNA topology and facilitates nuclear processes such as DNA replication, recombination, and repair. During these processes, topoisomerase I relieves torsional strain in DNA by inducing reversible single-strand breaks, allowing single DNA strands to pass through the break. The 3'-DNA terminus of the broken DNA strands bind covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After the DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the chemically unaltered topoisomers that allow transcription to proceed. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks. Current research suggests that the cytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either Irinotecan or SN-38. Mammalian cells cannot efficiently repair these double-strand breaks. The precise contribution of SN-38 to the activity of irinotecan in humans is not known. Irinotecan is cell cycle phase-specific (S-phase).
Mechanism of actionIrinotecan inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex. The formation of this ternary complex interferes with the moving replication fork, which induces replication arrest and lethal double-stranded breaks in DNA. As a result, DNA damage is not efficiently repaired and apoptosis (programmed cell death) occurs.
AbsorptionThe maximum plasma concentration (Cmax) when a dose of 125 mg/m^2 is given to patients with solid tumours is 1660 ng/mL. The AUC (0-24) is 10,200 ng·h/mL. The Cmax when a dose of 340 mg/m^2 is given to patients with solid tumours is 3392 ng/mL. The AUC (0-24) is 20,604 ng·h/mL.
Volume of distribution

The volume of distribution of terminal elimination phase is 110 L/m^2 when a dose of 125 mg/m^2 is given to patients with solid tumours. The volume of distribution of terminal elimination phase is 234 L/m^2 when a dose of 340 mg/m^2 is given to patients with solid tumours.

Protein binding30%-68% protein bound, mainly to albumin.
Metabolism

Hepatic. The metabolic conversion of irinotecan to the active metabolite SN-38 is mediated by carboxylesterase enzymes and primarily occurs in the liver. SN-38 is subsequently conjugated predominantly by the enzyme UDP-glucuronosyl transferase 1A1 (UGT1A1) to form a glucuronide metabolite.

SubstrateEnzymesProduct
Irinotecan
SN-38Details
Route of eliminationThe cumulative biliary and urinary excretion of irinotecan and its metabolites (SN-38 and SN-38 glucuronide) over a period of 48 hours following administration of irinotecan in two patients ranged from approximately 25% (100 mg/m2) to 50% (300 mg/m2).
Half lifeThe half life of irinotecan is about 6 - 12 hours. The terminal elimination half-life of the active metabolite, SN-38 is 10 - 20 hours.
Clearance
  • 13.3 L/h/m^2 [Dose of 125 mg/m^2, patients with solid tumours]
  • 13.9 L/h/m^2 [Dose of 340 mg/m^2, patients with solid tumours]
ToxicityGastrointestinal complications, such as nausea, vomiting, abdominal cramping, diarrhea, and infection.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Irinotecan Action PathwayDrug actionSMP00433
Irinotecan Metabolism PathwayDrug metabolismSMP00600
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
Solute carrier organic anion transporter family member 1B1
Gene symbol: SLCO1B1
UniProt: Q9Y6L6
rs4149056 SLCO1B1*15C AlleleDiarrhea, leucopenia, neutropenia17898662
Solute carrier organic anion transporter family member 1B1
Gene symbol: SLCO1B1
UniProt: Q9Y6L6
rs2306283 SLCO1B1*15G AlleleDiarrhea, leucopenia, neutropenia17898662
UDP-glucuronosyltransferase 1-1
Gene symbol: UGT1A1
UniProt: P22309
rs8175347 UGT1A1*28 or UGT1A 7/7extra TA in promoterLeukopenia, thrombpocytopenia17681105
UDP-glucuronosyltransferase 1-7
Gene symbol: UGT1A7
UniProt: Q9HAW7
rs17868323 Not AvailableG alleleLeukopenia, thrombpocytopenia18349289
UDP-glucuronosyltransferase 1-7
Gene symbol: UGT1A7
UniProt: Q9HAW7
rs17863778 Not AvailableA alleleLeukopenia, thrombpocytopenia18349289
UDP-glucuronosyltransferase 1-7
Gene symbol: UGT1A7
UniProt: Q9HAW7
rs17868324 Not AvailableA alleleLeukopenia, thrombpocytopenia18349289
UDP-glucuronosyltransferase 1-1
Gene symbol: UGT1A1
UniProt: P22309
rs10929302 Not AvailableA AlleleHematological toxicity, neutropenia17510208
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.969
Blood Brain Barrier+0.6284
Caco-2 permeable-0.6065
P-glycoprotein substrateSubstrate0.7861
P-glycoprotein inhibitor IInhibitor0.7092
P-glycoprotein inhibitor IINon-inhibitor0.5337
Renal organic cation transporterNon-inhibitor0.8178
CYP450 2C9 substrateNon-substrate0.8174
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateSubstrate0.7407
CYP450 1A2 substrateNon-inhibitor0.8564
CYP450 2C9 substrateNon-inhibitor0.7377
CYP450 2D6 substrateNon-inhibitor0.7779
CYP450 2C19 substrateNon-inhibitor0.6625
CYP450 3A4 substrateInhibitor0.8295
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5081
Ames testNon AMES toxic0.6977
CarcinogenicityNon-carcinogens0.8045
BiodegradationNot ready biodegradable0.9956
Rat acute toxicity2.7960 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9457
hERG inhibition (predictor II)Inhibitor0.5413
Pharmacoeconomics
Manufacturers
  • Pfizer inc
  • Accord healthcare inc
  • Actavis totowa llc
  • Akorn inc
  • App pharmaceuticals
  • Bedford laboratories
  • Dr reddys laboratories ltd
  • Ebewe pharma ges mbh nfg kg
  • Fresenius kabi oncology plc
  • Hospira inc
  • Pharmaforce inc
  • Pliva lachema as
  • Sandoz inc
  • Sun pharma global inc
  • Teva parenteral medicines inc
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
Injectionintravenous100 mg/5mL
Injectionintravenous20 mg/mL
Injectionintravenous40 mg/2mL
Injection, solutionintravenous100 mg/5mL
Injection, solutionintravenous20 mg/mL
Injection, solutionintravenous40 mg/2mL
Solutionintravenous20 mg
Prices
Unit descriptionCostUnit
Irinotecan hcl 40 mg/2 ml inj138.07USD ml
Camptosar 20 mg/ml vial36.0USD ml
Irinotecan hcl 40 mg/2 ml vial22.2USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada22025312005-05-032015-10-11
Canada22940312005-01-182018-07-27
United States64035692000-04-282020-04-28
United States67943702000-11-012020-11-01
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point222-223 °CNot Available
water solubilitySolubleNot Available
logP3.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.107 mg/mLALOGPS
logP3.94ALOGPS
logP2.78ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)11.71ChemAxon
pKa (Strongest Basic)9.47ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area112.51 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity161.33 m3·mol-1ChemAxon
Polarizability65.27 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US4604463
General Reference
  1. Innocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M, Karrison T, Janisch L, Ramirez J, Rudin CM, Vokes EE, Ratain MJ: Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol. 2004 Apr 15;22(8):1382-8. Epub 2004 Mar 8. Pubmed
  2. O’Dwyer PJ, Catalano RB: Uridine diphosphate glucuronosyltransferase (UGT) 1A1 and irinotecan: practical pharmacogenomics arrives in cancer therapy. J Clin Oncol. 2006 Oct 1;24(28):4534-8. Pubmed
  3. Ramesh M, Ahlawat P, Srinivas NR: Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010 Jan;24(1):104-23. Pubmed
  4. Chabot GG: Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet. 1997 Oct;33(4):245-59. Pubmed
  5. FDA label
External Links
ATC CodesL01XX19
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelDownload (132 KB)
MSDSDownload (36.3 KB)
Interactions
Drug Interactions
Drug
AprepitantMay increase the serum concentration of CYP3A4 Substrates.
AtazanavirCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
BevacizumabBevacizumab may enhance the adverse/toxic effect of Irinotecan.
BoceprevirCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
BosentanMay decrease the serum concentration of CYP3A4 Substrates.
CarbamazepineCYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan.
ClarithromycinCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
ClozapineMyelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for agranulocytosis may be increased.
ConivaptanMay increase the serum concentration of CYP3A4 Substrates.
DabrafenibMay decrease the serum concentration of CYP3A4 Substrates.
DarunavirCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
DasatinibMay increase the serum concentration of CYP3A4 Substrates.
DeferasiroxMay decrease the serum concentration of CYP3A4 Substrates.
DelavirdineCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
DenosumabMay enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
EltrombopagMay increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
EnzalutamideCYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan.
FosamprenavirCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
FosaprepitantMay increase the serum concentration of CYP3A4 Substrates.
FosphenytoinCYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan.
GemfibrozilMay increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased.
IndinavirCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
ItraconazoleCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
IvacaftorMay increase the serum concentration of CYP3A4 Substrates.
LeflunomideImmunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased.
LopinavirCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
LULICONAZOLEMay increase the serum concentration of CYP3A4 Substrates.
MifepristoneMay increase the serum concentration of CYP3A4 Substrates.
NatalizumabImmunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
NefazodoneCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
NelfinavirCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
PhenobarbitalCYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan.
PhenytoinCYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan.
PimecrolimusMay enhance the adverse/toxic effect of Immunosuppressants.
PosaconazoleCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
PrimidoneCYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan.
QuazepamMay increase the serum concentration of CYP2B6 Substrates.
RegorafenibMay increase serum concentrations of the active metabolite(s) of Irinotecan. Regorafenib may increase the serum concentration of Irinotecan.
RifampicinCYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan.
RifapentineCYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan.
RitonavirCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
RoflumilastMay enhance the immunosuppressive effect of Immunosuppressants.
SaquinavirCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
SiltuximabMay decrease the serum concentration of CYP3A4 Substrates.
SimeprevirMay increase the serum concentration of CYP3A4 Substrates.
Sipuleucel-TImmunosuppressants may diminish the therapeutic effect of Sipuleucel-T.
SorafenibSORAfenib may increase the serum concentration of Irinotecan. Sorafenib may also increase the concentration of the active metabolite of irinotecan, SN-38.
TelaprevirCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
TelithromycinCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
TeriflunomideMay increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
TocilizumabMay decrease the serum concentration of CYP3A4 Substrates.
TofacitinibImmunosuppressants may enhance the immunosuppressive effect of Tofacitinib.
TrastuzumabMay enhance the neutropenic effect of Immunosuppressants.
VoriconazoleCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
Food InteractionsNot Available

Targets

1. DNA topoisomerase I, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
DNA topoisomerase I, mitochondrial Q969P6 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Yoshikawa M, Ikegami Y, Hayasaka S, Ishii K, Ito A, Sano K, Suzuki T, Togawa T, Yoshida H, Soda H, Oka M, Kohno S, Sawada S, Ishikawa T, Tanabe S: Novel camptothecin analogues that circumvent ABCG2-associated drug resistance in human tumor cells. Int J Cancer. 2004 Jul 20;110(6):921-7. Pubmed
  4. Yoshikawa M, Ikegami Y, Sano K, Yoshida H, Mitomo H, Sawada S, Ishikawa T: Transport of SN-38 by the wild type of human ABC transporter ABCG2 and its inhibition by quercetin, a natural flavonoid. J Exp Ther Oncol. 2004 Apr;4(1):25-35. Pubmed
  5. Yang X, Hu Z, Chan SY, Chan E, Goh BC, Duan W, Zhou S: Novel agents that potentially inhibit irinotecan-induced diarrhea. Curr Med Chem. 2005;12(11):1343-58. Pubmed
  6. Nakagawa H, Saito H, Ikegami Y, Aida-Hyugaji S, Sawada S, Ishikawa T: Molecular modeling of new camptothecin analogues to circumvent ABCG2-mediated drug resistance in cancer. Cancer Lett. 2006 Mar 8;234(1):81-9. Epub 2005 Nov 23. Pubmed
  7. Ishikawa T, Ikegami Y, Sano K, Nakagawa H, Sawada S: Transport mechanism-based drug molecular design: novel camptothecin analogues to circumvent ABCG2-associated drug resistance of human tumor cells. Curr Pharm Des. 2006;12(3):313-25. Pubmed
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  9. Ramesh M, Ahlawat P, Srinivas NR: Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010 Jan;24(1):104-23. Pubmed
  10. Chabot GG: Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet. 1997 Oct;33(4):245-59. Pubmed

2. DNA topoisomerase 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
DNA topoisomerase 1 P11387 Details

References:

  1. Yoshikawa M, Ikegami Y, Hayasaka S, Ishii K, Ito A, Sano K, Suzuki T, Togawa T, Yoshida H, Soda H, Oka M, Kohno S, Sawada S, Ishikawa T, Tanabe S: Novel camptothecin analogues that circumvent ABCG2-associated drug resistance in human tumor cells. Int J Cancer. 2004 Jul 20;110(6):921-7. Pubmed
  2. Yoshikawa M, Ikegami Y, Sano K, Yoshida H, Mitomo H, Sawada S, Ishikawa T: Transport of SN-38 by the wild type of human ABC transporter ABCG2 and its inhibition by quercetin, a natural flavonoid. J Exp Ther Oncol. 2004 Apr;4(1):25-35. Pubmed
  3. Yang X, Hu Z, Chan SY, Chan E, Goh BC, Duan W, Zhou S: Novel agents that potentially inhibit irinotecan-induced diarrhea. Curr Med Chem. 2005;12(11):1343-58. Pubmed
  4. Nakagawa H, Saito H, Ikegami Y, Aida-Hyugaji S, Sawada S, Ishikawa T: Molecular modeling of new camptothecin analogues to circumvent ABCG2-mediated drug resistance in cancer. Cancer Lett. 2006 Mar 8;234(1):81-9. Epub 2005 Nov 23. Pubmed
  5. Ishikawa T, Ikegami Y, Sano K, Nakagawa H, Sawada S: Transport mechanism-based drug molecular design: novel camptothecin analogues to circumvent ABCG2-associated drug resistance of human tumor cells. Curr Pharm Des. 2006;12(3):313-25. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  7. Ramesh M, Ahlawat P, Srinivas NR: Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010 Jan;24(1):104-23. Pubmed
  8. Chabot GG: Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet. 1997 Oct;33(4):245-59. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Ramesh M, Ahlawat P, Srinivas NR: Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010 Jan;24(1):104-23. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  4. Kuhn JG: Pharmacology of irinotecan. Oncology (Williston Park). 1998 Aug;12(8 Suppl 6):39-42. Pubmed

2. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2B6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

5. UDP-glucuronosyltransferase 1-1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
UDP-glucuronosyltransferase 1-1 P22309 Details

References:

  1. Kuhn JG: Pharmacology of irinotecan. Oncology (Williston Park). 1998 Aug;12(8 Suppl 6):39-42. Pubmed

6. UDP-glucuronosyltransferase 1-9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
UDP-glucuronosyltransferase 1-9 O60656 Details

References:

  1. Chabot GG: Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet. 1997 Oct;33(4):245-59. Pubmed

7. Liver carboxylesterase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Liver carboxylesterase 1 P23141 Details

References:

  1. Chabot GG: Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet. 1997 Oct;33(4):245-59. Pubmed
  2. Ramesh M, Ahlawat P, Srinivas NR: Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010 Jan;24(1):104-23. Pubmed
  3. Kuhn JG: Pharmacology of irinotecan. Oncology (Williston Park). 1998 Aug;12(8 Suppl 6):39-42. Pubmed

8. Cocaine esterase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cocaine esterase O00748 Details

References:

  1. Sanghani SP, Quinney SK, Fredenburg TB, Davis WI, Murry DJ, Bosron WF: Hydrolysis of irinotecan and its oxidative metabolites, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin and 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin, by human carboxylesterases CES1A1, CES2, and a newly expressed carboxylesterase isoenzyme, CES3. Drug Metab Dispos. 2004 May;32(5):505-11. Pubmed

9. Cholinesterase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cholinesterase P06276 Details

References:

  1. https://www.pharmgkb.org/pathway/PA2029

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. FDA label

Transporters

1. Solute carrier family 22 member 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 3 O75751 Details

References:

  1. Shnitsar V, Eckardt R, Gupta S, Grottker J, Muller GA, Koepsell H, Burckhardt G, Hagos Y: Expression of human organic cation transporter 3 in kidney carcinoma cell lines increases chemosensitivity to melphalan, irinotecan, and vincristine. Cancer Res. 2009 Feb 15;69(4):1494-501. Epub 2009 Feb 3. Pubmed

2. Solute carrier organic anion transporter family member 1B1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1B1 Q9Y6L6 Details

References:

  1. Nozawa T, Minami H, Sugiura S, Tsuji A, Tamai I: Role of organic anion transporter OATP1B1 (OATP-C) in hepatic uptake of irinotecan and its active metabolite, 7-ethyl-10-hydroxycamptothecin: in vitro evidence and effect of single nucleotide polymorphisms. Drug Metab Dispos. 2005 Mar;33(3):434-9. Epub 2004 Dec 17. Pubmed

3. Multidrug resistance-associated protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance-associated protein 1 P33527 Details

References:

  1. Chen ZS, Furukawa T, Sumizawa T, Ono K, Ueda K, Seto K, Akiyama SI: 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. Pubmed

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

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

References:

  1. Wang X, Furukawa T, Nitanda T, Okamoto M, Sugimoto Y, Akiyama S, Baba M: Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Mol Pharmacol. 2003 Jan;63(1):65-72. Pubmed
  2. Maliepaard M, van Gastelen MA, Tohgo A, Hausheer FH, van Waardenburg RC, de Jong LA, Pluim D, Beijnen JH, Schellens JH: Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918. Clin Cancer Res. 2001 Apr;7(4):935-41. Pubmed

5. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Kroetz DL: Role for drug transporters beyond tumor resistance: hepatic functional imaging and genotyping of multidrug resistance transporters for the prediction of irinotecan toxicity. J Clin Oncol. 2006 Sep 10;24(26):4225-7. Epub 2006 Aug 8. Pubmed
  2. Han JY, Lim HS, Park YH, Lee SY, Lee JS: Integrated pharmacogenetic prediction of irinotecan pharmacokinetics and toxicity in patients with advanced non-small cell lung cancer. Lung Cancer. 2009 Jan;63(1):115-20. doi: 10.1016/j.lungcan.2007.12.003. Epub 2008 Jan 24. Pubmed

6. Canalicular multispecific organic anion transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

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

References:

  1. Kroetz DL: Role for drug transporters beyond tumor resistance: hepatic functional imaging and genotyping of multidrug resistance transporters for the prediction of irinotecan toxicity. J Clin Oncol. 2006 Sep 10;24(26):4225-7. Epub 2006 Aug 8. Pubmed
  2. Han JY, Lim HS, Park YH, Lee SY, Lee JS: Integrated pharmacogenetic prediction of irinotecan pharmacokinetics and toxicity in patients with advanced non-small cell lung cancer. Lung Cancer. 2009 Jan;63(1):115-20. doi: 10.1016/j.lungcan.2007.12.003. Epub 2008 Jan 24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:24