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Identification
NameErlotinib
Accession NumberDB00530  (APRD00951)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Erlotinib hydrochloride (trade name Tarceva, Genentech/OSIP, originally coded as OSI-774) is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer.

Similar to gefitinib, erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor. Erlotinib has recently been shown to be a potent inhibitor of JAK2V617F activity. JAK2V617F is a mutant of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial proportion of patients with idiopathic myelofibrosis or essential thrombocythemia. The study suggests that erlotinib may be used for treatment of JAK2V617F-positive PV and other myeloproliferative disorders.

Structure
Thumb
Synonyms
[6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4-yl]-(3-ethynyl-phenyl)-amine
Erlotinib
OSI-774
External Identifiers
  • CP358774
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Tarcevatablet25 mg/1oralGenentech, Inc.2005-04-30Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tarcevatablet25 mgoralHoffmann La Roche Limited2007-01-05Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Tarcevatablet100 mg/1oralAvera Mc Kennan Hospital2015-04-01Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tarcevatablet100 mg/1oralPhysicians Total Care, Inc.2005-11-21Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tarcevatablet150 mg/1oralPhysicians Total Care, Inc.2005-10-13Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tarcevatablet25 mg/1oralPhysicians Total Care, Inc.2005-07-01Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tarcevatablet150 mg/1oralGenentech, Inc.2005-04-30Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tarcevatablet150 mgoralHoffmann La Roche Limited2005-07-19Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Tarcevatablet100 mg/1oralGenentech, Inc.2005-04-30Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Tarcevatablet100 mgoralHoffmann La Roche Limited2005-07-19Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Teva-erlotinibtablet150 mgoralTeva Canada Limited2014-12-08Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Teva-erlotinibtablet100 mgoralTeva Canada Limited2014-12-08Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Teva-erlotinibtablet25 mgoralTeva Canada Limited2014-12-08Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Erlotinib Hydrochloride
183319-69-9
Thumb
  • InChI Key: GTTBEUCJPZQMDZ-UHFFFAOYSA-N
  • Monoisotopic Mass: 429.145533978
  • Average Mass: 429.897
DBSALT000064
Categories
CAS number183321-74-6
WeightAverage: 393.4357
Monoisotopic: 393.168856239
Chemical FormulaC22H23N3O4
InChI KeyInChIKey=AAKJLRGGTJKAMG-UHFFFAOYSA-N
InChI
InChI=1S/C22H23N3O4/c1-4-16-6-5-7-17(12-16)25-22-18-13-20(28-10-8-26-2)21(29-11-9-27-3)14-19(18)23-15-24-22/h1,5-7,12-15H,8-11H2,2-3H3,(H,23,24,25)
IUPAC Name
N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine
SMILES
COCCOC1=C(OCCOC)C=C2C(NC3=CC=CC(=C3)C#C)=NC=NC2=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassNaphthyridines
Sub ClassQuinazolines
Direct ParentQuinazolinamines
Alternative Parents
Substituents
  • Quinazolinamine
  • Aminopyrimidine
  • Alkyl aryl ether
  • Imidolactam
  • Benzenoid
  • Pyrimidine
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Azacycle
  • Secondary amine
  • Ether
  • Dialkyl ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Also for use, in combination with gemcitabine, as the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer.
PharmacodynamicsNot Available
Mechanism of actionThe mechanism of clinical antitumor action of erlotinib is not fully characterized. Erlotinib inhibits the intracellular phosphorylation of tyrosine kinase associated with the epidermal growth factor receptor (EGFR). Specificity of inhibition with regard to other tyrosine kinase receptors has not been fully characterized. EGFR is expressed on the cell surface of normal cells and cancer cells.
AbsorptionErlotinib is about 60% absorbed after oral administration and its bioavailability is substantially increased by food to almost 100%. Peak plasma levels occur 4 hours after dosing. The solubility of erlotinib is pH dependent. Solubility decreases pH increases. Smoking also decrease the exposure of erlotinib.
Volume of distribution

Apparent volume of distribution = 232 L

Protein binding93% protein bound to albumin and alpha-1 acid glycoprotein (AAG)
Metabolism

Metabolism occurs in the liver. In vitro assays of cytochrome P450 metabolism showed that erlotinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2, and the extrahepatic isoform CYP1A1.

Route of eliminationFollowing a 100 mg oral dose, 91% of the dose was recovered in which 83% was in feces (1% of the dose as unchanged parent compound) and 8% in urine (0.3% of the dose as unchanged parent compound).
Half lifeMedian half-life of 36.2 hours.
Clearance

Smokers have a 24% higher rate of erlotinib clearance.

ToxicitySymptoms of overdose include diarrhea, rash, and liver transaminase elevation. The most common adverse reactions (>50%) in NSCLC are rash, diarrhea, anorexia and fatigue. The most common adverse reactions (>50%) in pancreatic cancer are fatigue, rash, nausea and anorexia.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated Effects
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
Epidermal growth factor receptor
Gene symbol: EGFR
UniProt: P00533
Not AvailableG719A/C OR (L858R and L861Q)Not AvailableAssociated with enhanced activation of the EGFR tyrosine kinase in patients with non-small cell lung cancer (NSCLC) recieving tyrosine kinase inhibitor therapy.15118073
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9359
Blood Brain Barrier+0.9376
Caco-2 permeable+0.5737
P-glycoprotein substrateSubstrate0.5982
P-glycoprotein inhibitor IInhibitor0.5958
P-glycoprotein inhibitor IINon-inhibitor0.6169
Renal organic cation transporterNon-inhibitor0.7171
CYP450 2C9 substrateNon-substrate0.7942
CYP450 2D6 substrateNon-substrate0.7611
CYP450 3A4 substrateSubstrate0.5886
CYP450 1A2 substrateInhibitor0.7826
CYP450 2C9 inhibitorNon-inhibitor0.5739
CYP450 2D6 inhibitorNon-inhibitor0.6329
CYP450 2C19 inhibitorInhibitor0.598
CYP450 3A4 inhibitorInhibitor0.7194
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7911
Ames testAMES toxic0.5195
CarcinogenicityNon-carcinogens0.9551
BiodegradationNot ready biodegradable0.9907
Rat acute toxicity2.3958 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8158
hERG inhibition (predictor II)Non-inhibitor0.6776
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Osi pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
Tabletoral100 mg/1
Tabletoral100 mg
Tabletoral150 mg/1
Tabletoral150 mg
Tabletoral25 mg/1
Tabletoral25 mg
Prices
Unit descriptionCostUnit
Tarceva 150 mg tablet163.98USD tablet
Tarceva 100 mg tablet144.98USD tablet
Tarceva 25 mg tablet52.78USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada22167962003-09-022015-06-06
Canada25149772010-06-222024-02-11
United States57474981998-11-082018-11-08
United States69002212000-11-092020-11-09
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityVery slightly soluble (hydrochloride salt - maximal solubility of approximately 0.4 mg/mL occurs at a pH of approximately 2)Not Available
logP2.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00891 mg/mLALOGPS
logP3.13ALOGPS
logP3.2ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)16.14ChemAxon
pKa (Strongest Basic)4.59ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area74.73 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity107.79 m3·mol-1ChemAxon
Polarizability43.48 Å3ChemAxon
Number of Rings3ChemAxon
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

US5747498
General References
  1. Raymond E, Faivre S, Armand JP: Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy. Drugs. 2000;60 Suppl 1:15-23; discussion 41-2. Pubmed
  2. Li Z, Xu M, Xing S, Ho WT, Ishii T, Li Q, Fu X, Zhao ZJ: Erlotinib effectively inhibits JAK2V617F activity and polycythemia vera cell growth. J Biol Chem. 2007 Feb 9;282(6):3428-32. Epub 2006 Dec 18. Pubmed
  3. Dudek AZ, Kmak KL, Koopmeiners J, Keshtgarpour M: Skin rash and bronchoalveolar histology correlates with clinical benefit in patients treated with gefitinib as a therapy for previously treated advanced or metastatic non-small cell lung cancer. Lung Cancer. 2006 Jan;51(1):89-96. Epub 2005 Nov 14. Pubmed
  4. Jones HE, Goddard L, Gee JM, Hiscox S, Rubini M, Barrow D, Knowlden JM, Williams S, Wakeling AE, Nicholson RI: Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells. Endocr Relat Cancer. 2004 Dec;11(4):793-814. Pubmed
  5. Blum G, Gazit A, Levitzki A: Substrate competitive inhibitors of IGF-1 receptor kinase. Biochemistry. 2000 Dec 26;39(51):15705-12. Pubmed
External Links
ATC CodesL01XE03
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelDownload (999 KB)
MSDSDownload (107 KB)
Interactions
Drug Interactions
Drug
Aluminum hydroxideThe serum concentration of Erlotinib can be decreased when it is combined with Aluminum hydroxide.
AprepitantThe serum concentration of Erlotinib can be increased when it is combined with Aprepitant.
AtazanavirThe serum concentration of Erlotinib can be increased when it is combined with Atazanavir.
BexaroteneThe serum concentration of Erlotinib can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Erlotinib can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Erlotinib can be decreased when it is combined with Bosentan.
Calcium carbonateThe serum concentration of Erlotinib can be decreased when it is combined with Calcium carbonate.
CarbamazepineThe serum concentration of Erlotinib can be decreased when it is combined with Carbamazepine.
CeritinibThe serum concentration of Erlotinib can be increased when it is combined with Ceritinib.
CimetidineThe serum concentration of Erlotinib can be decreased when it is combined with Cimetidine.
CiprofloxacinThe serum concentration of Erlotinib can be increased when it is combined with Ciprofloxacin.
ClarithromycinThe serum concentration of Erlotinib can be increased when it is combined with Clarithromycin.
CobicistatThe serum concentration of Erlotinib can be increased when it is combined with Cobicistat.
ConivaptanThe serum concentration of Erlotinib can be increased when it is combined with Conivaptan.
DabrafenibThe serum concentration of Erlotinib can be decreased when it is combined with Dabrafenib.
DarunavirThe serum concentration of Erlotinib can be increased when it is combined with Darunavir.
DasatinibThe serum concentration of Erlotinib can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Erlotinib can be decreased when it is combined with Deferasirox.
EnzalutamideThe serum concentration of Erlotinib can be decreased when it is combined with Enzalutamide.
EsomeprazoleThe serum concentration of Erlotinib can be decreased when it is combined with Esomeprazole.
FamotidineThe serum concentration of Erlotinib can be decreased when it is combined with Famotidine.
FluconazoleThe metabolism of Erlotinib can be decreased when combined with Fluconazole.
FluvoxamineThe serum concentration of Erlotinib can be increased when it is combined with Fluvoxamine.
FosaprepitantThe serum concentration of Erlotinib can be increased when it is combined with Fosaprepitant.
FosphenytoinThe serum concentration of Erlotinib can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Erlotinib can be increased when it is combined with Fusidic Acid.
IdelalisibThe serum concentration of Erlotinib can be increased when it is combined with Idelalisib.
IndinavirThe serum concentration of Erlotinib can be increased when it is combined with Indinavir.
IrinotecanThe serum concentration of the active metabolites of Irinotecan can be increased when Irinotecan is used in combination with Erlotinib.
ItraconazoleThe serum concentration of Erlotinib can be increased when it is combined with Itraconazole.
IvacaftorThe serum concentration of Erlotinib can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Erlotinib can be increased when it is combined with Ketoconazole.
LansoprazoleThe serum concentration of Erlotinib can be decreased when it is combined with Lansoprazole.
LuliconazoleThe serum concentration of Erlotinib can be increased when it is combined with Luliconazole.
Magnesium hydroxideThe serum concentration of Erlotinib can be decreased when it is combined with Magnesium hydroxide.
Magnesium oxideThe serum concentration of Erlotinib can be decreased when it is combined with Magnesium oxide.
MifepristoneThe serum concentration of Erlotinib can be increased when it is combined with Mifepristone.
MitotaneThe serum concentration of Erlotinib can be decreased when it is combined with Mitotane.
NefazodoneThe serum concentration of Erlotinib can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Erlotinib can be increased when it is combined with Nelfinavir.
NetupitantThe serum concentration of Erlotinib can be increased when it is combined with Netupitant.
NizatidineThe serum concentration of Erlotinib can be decreased when it is combined with Nizatidine.
OmeprazoleThe serum concentration of Erlotinib can be decreased when it is combined with Omeprazole.
PalbociclibThe serum concentration of Erlotinib can be increased when it is combined with Palbociclib.
PantoprazoleThe serum concentration of Erlotinib can be decreased when it is combined with Pantoprazole.
PhenobarbitalThe serum concentration of Erlotinib can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Erlotinib can be decreased when it is combined with Phenytoin.
PosaconazoleThe serum concentration of Erlotinib can be increased when it is combined with Posaconazole.
PrimidoneThe serum concentration of Erlotinib can be decreased when it is combined with Primidone.
RabeprazoleThe serum concentration of Erlotinib can be decreased when it is combined with Rabeprazole.
RanitidineThe serum concentration of Erlotinib can be decreased when it is combined with Ranitidine.
RifabutinThe serum concentration of Erlotinib can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Erlotinib can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Erlotinib can be decreased when it is combined with Rifapentine.
RitonavirThe serum concentration of Erlotinib can be increased when it is combined with Ritonavir.
SaquinavirThe serum concentration of Erlotinib can be increased when it is combined with Saquinavir.
SiltuximabThe serum concentration of Erlotinib can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Erlotinib can be increased when it is combined with Simeprevir.
Sodium bicarbonateThe serum concentration of Erlotinib can be decreased when it is combined with Sodium bicarbonate.
St. John's WortThe serum concentration of Erlotinib can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Erlotinib can be increased when it is combined with Stiripentol.
TelaprevirThe serum concentration of Erlotinib can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Erlotinib can be increased when it is combined with Telithromycin.
TocilizumabThe serum concentration of Erlotinib can be decreased when it is combined with Tocilizumab.
VoriconazoleThe serum concentration of Erlotinib can be increased when it is combined with Voriconazole.
WarfarinThe serum concentration of Warfarin can be increased when it is combined with Erlotinib.
Food Interactions
  • Take at least 1 hour before or 2 hours after any food.
  • Take with a glass of water.

Targets

1. Epidermal growth factor receptor

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Epidermal growth factor receptor P00533 Details

References:

  1. Kim TE, Murren JR: Erlotinib OSI/Roche/Genentech. Curr Opin Investig Drugs. 2002 Sep;3(9):1385-95. Pubmed
  2. Laird AD, Cherrington JM: Small molecule tyrosine kinase inhibitors: clinical development of anticancer agents. Expert Opin Investig Drugs. 2003 Jan;12(1):51-64. Pubmed
  3. Delbaldo C, Faivre S, Raymond E: [Epidermal growth factor inhibitors] Rev Med Interne. 2003 Jun;24(6):372-83. Pubmed
  4. Bulgaru AM, Mani S, Goel S, Perez-Soler R: Erlotinib (Tarceva): a promising drug targeting epidermal growth factor receptor tyrosine kinase. Expert Rev Anticancer Ther. 2003 Jun;3(3):269-79. Pubmed
  5. Akita RW, Sliwkowski MX: Preclinical studies with Erlotinib (Tarceva). Semin Oncol. 2003 Jun;30(3 Suppl 7):15-24. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Nuclear receptor subfamily 1 group I member 2

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Nuclear receptor subfamily 1 group I member 2 O75469 Details

References:

  1. Harmsen S, Meijerman I, Beijnen JH, Schellens JH: Nuclear receptor mediated induction of cytochrome P450 3A4 by anticancer drugs: a key role for the pregnane X receptor. Cancer Chemother Pharmacol. 2009 Jun;64(1):35-43. Epub 2008 Oct 7. Pubmed
  2. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. Epub 2009 Sep 5. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. Epub 2009 Sep 5. Pubmed
  2. Johnson JR, Cohen M, Sridhara R, Chen YF, Williams GM, Duan J, Gobburu J, Booth B, Benson K, Leighton J, Hsieh LS, Chidambaram N, Zimmerman P, Pazdur R: Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Clin Cancer Res. 2005 Sep 15;11(18):6414-21. Pubmed
  3. Li J, Zhao M, He P, Hidalgo M, Baker SD: Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res. 2007 Jun 15;13(12):3731-7. Pubmed
  4. Hamilton M, Wolf JL, Rusk J, Beard SE, Clark GM, Witt K, Cagnoni PJ: Effects of smoking on the pharmacokinetics of erlotinib. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2166-71. 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. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. Epub 2009 Sep 5. Pubmed
  2. Li J, Zhao M, He P, Hidalgo M, Baker SD: Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res. 2007 Jun 15;13(12):3731-7. Pubmed

3. Cytochrome P450 1A2

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. Epub 2009 Sep 5. Pubmed
  2. Lu JF, Eppler SM, Wolf J, Hamilton M, Rakhit A, Bruno R, Lum BL: Clinical pharmacokinetics of erlotinib in patients with solid tumors and exposure-safety relationship in patients with non-small cell lung cancer. Clin Pharmacol Ther. 2006 Aug;80(2):136-45. Pubmed
  3. Johnson JR, Cohen M, Sridhara R, Chen YF, Williams GM, Duan J, Gobburu J, Booth B, Benson K, Leighton J, Hsieh LS, Chidambaram N, Zimmerman P, Pazdur R: Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Clin Cancer Res. 2005 Sep 15;11(18):6414-21. Pubmed
  4. Li J, Zhao M, He P, Hidalgo M, Baker SD: Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res. 2007 Jun 15;13(12):3731-7. Pubmed
  5. Hamilton M, Wolf JL, Rusk J, Beard SE, Clark GM, Witt K, Cagnoni PJ: Effects of smoking on the pharmacokinetics of erlotinib. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2166-71. Pubmed

4. Cytochrome P450 1A1

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

References:

  1. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. Epub 2009 Sep 5. Pubmed
  2. Johnson JR, Cohen M, Sridhara R, Chen YF, Williams GM, Duan J, Gobburu J, Booth B, Benson K, Leighton J, Hsieh LS, Chidambaram N, Zimmerman P, Pazdur R: Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Clin Cancer Res. 2005 Sep 15;11(18):6414-21. Pubmed
  3. Li J, Zhao M, He P, Hidalgo M, Baker SD: Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res. 2007 Jun 15;13(12):3731-7. Pubmed

5. Cytochrome P450 2D6

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. Epub 2009 Sep 5. Pubmed
  2. Li J, Zhao M, He P, Hidalgo M, Baker SD: Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res. 2007 Jun 15;13(12):3731-7. Pubmed

6. Cytochrome P450 2C8

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. Epub 2009 Sep 5. Pubmed
  2. Hamilton M, Wolf JL, Rusk J, Beard SE, Clark GM, Witt K, Cagnoni PJ: Effects of smoking on the pharmacokinetics of erlotinib. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2166-71. Pubmed

7. Cytochrome P450 1B1

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1B1 Q16678 Details

References:

  1. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. Epub 2009 Sep 5. Pubmed
  2. Li J, Zhao M, He P, Hidalgo M, Baker SD: Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res. 2007 Jun 15;13(12):3731-7. Pubmed

8. UDP-glucuronosyltransferase 1-1

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

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

References:

  1. Liu Y, Ramirez J, House L, Ratain MJ: The UGT1A1*28 polymorphism correlates with erlotinib’s effect on SN-38 glucuronidation. Eur J Cancer. 2010 Jul;46(11):2097-103. doi: 10.1016/j.ejca.2010.04.022. Epub 2010 May 23. Pubmed

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

2. Alpha-1-acid glycoprotein 1

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Alpha-1-acid glycoprotein 1 P02763 Details

References:

  1. FDA label

Transporters

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

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

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

References:

  1. Noguchi K, Kawahara H, Kaji A, Katayama K, Mitsuhashi J, Sugimoto Y: Substrate-dependent bidirectional modulation of P-glycoprotein-mediated drug resistance by erlotinib. Cancer Sci. 2009 Sep;100(9):1701-7. Epub 2009 May 12. Pubmed

2. 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. Marchetti S, de Vries NA, Buckle T, Bolijn MJ, van Eijndhoven MA, Beijnen JH, Mazzanti R, van Tellingen O, Schellens JH: Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on erlotinib hydrochloride (Tarceva) disposition in in vitro and in vivo pharmacokinetic studies employing Bcrp1-/-/Mdr1a/1b-/- (triple-knockout) and wild-type mice. Mol Cancer Ther. 2008 Aug;7(8):2280-7. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:23