Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C22H24ClFN4O3 |
| Molecular Weight | 446.902 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC2=NC=NC(NC3=CC(Cl)=C(F)C=C3)=C2C=C1OCCCN4CCOCC4
InChI
InChIKey=XGALLCVXEZPNRQ-UHFFFAOYSA-N
InChI=1S/C22H24ClFN4O3/c1-29-20-13-19-16(12-21(20)31-8-2-5-28-6-9-30-10-7-28)22(26-14-25-19)27-15-3-4-18(24)17(23)11-15/h3-4,11-14H,2,5-10H2,1H3,(H,25,26,27)
| Molecular Formula | C22H24ClFN4O3 |
| Molecular Weight | 446.902 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionSources: http://www.drugbank.ca/drugs/DB00317Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/cdi/gefitinib.html
Sources: http://www.drugbank.ca/drugs/DB00317
Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/cdi/gefitinib.html
Gefitinib is an anilinoquinazoline with antineoplastic activity. Gefitinib inhibits the epidermal growth factor receptor (EGFR) tyrosine kinase by binding to the adenosine triphosphate (ATP)-binding site of the enzyme. Thus the function of the EGFR tyrosine kinase in activating the Ras signal transduction cascade is inhibited; and malignant cells are inhibited. Gefitinib is the first selective inhibitor of the EGFR tyrosine kinase which is also referred to as Her1 or ErbB-1. EGFR is overexpressed in the cells of certain types of human carcinomas - for example in lung and breast cancers. Overexpression leads to inappropriate activation of the apoptotic Ras signal transduction cascade, eventually leading to uncontrolled cell proliferation. Gefitinib is used for the continued treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of either platinum-based or docetaxel chemotherapies.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22846582
Curator's Comment: low penetration in humans
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21334203 |
1.0 nM [IC50] | ||
Target ID: CHEMBL614526 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26703559 |
19.27 µM [IC50] | ||
Target ID: CHEMBL614348 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27118497 |
1.23 µM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Iressa Approved UseIRESSA is indicated as monotherapy for the continued treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of both platinum-based and docetaxel chemotherapies who are benefiting or have benefited from IRESSA. Launch Date2003 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
57.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21487718 |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEFITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
724 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28579188 |
250 mg 1 times / day steady-state, oral dose: 250 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
213 ng/mL |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEFITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
2160 ng/mL |
700 mg 1 times / day multiple, oral dose: 700 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
579 ng/mL |
400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
178 ng/mL |
100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
57.45 ng/mL |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
2210 ng/mL |
400 mg/m² 1 times / day multiple, oral dose: 400 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN |
|
466 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21487718 |
250 mg 1 times / day steady-state, oral dose: 250 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
GEFITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1415 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21487718 |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEFITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
13103 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28579188 |
250 mg 1 times / day steady-state, oral dose: 250 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
6181 ng × h/mL |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEFITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
42314 ng × h/mL |
700 mg 1 times / day multiple, oral dose: 700 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
10026 ng × h/mL |
400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
2985 ng × h/mL |
100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
1415 ng × h/mL |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
29.3 μg × h/mL |
400 mg/m² 1 times / day multiple, oral dose: 400 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN |
|
8896 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21487718 |
250 mg 1 times / day steady-state, oral dose: 250 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
GEFITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
21.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21487718 |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEFITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
25 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28579188 |
250 mg 1 times / day steady-state, oral dose: 250 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
28.2 h |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEFITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
72.9 h |
700 mg 1 times / day multiple, oral dose: 700 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
38.1 h |
400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
55.2 h |
100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
23.83 h |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
11.9 h |
400 mg/m² 1 times / day multiple, oral dose: 400 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered: |
GEFITINIB plasma | Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
9% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21487718 |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEFITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
10% |
GEFITINIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| yes [Inhibition 11.2 uM] | yes (co-administration study) Comment: gefitinib increased auc of metoprolol by 35% |
|||
| yes |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| major | yes (co-administration study) Comment: itraconazole increased auc of gefitinib by 80% |
|||
Page: 21.0 |
major | yes (pharmacogenomic study) Comment: CYP2D6 PMs have approximately 2-fold higher exposure to gefitinib than CYP2D6 EM Page: 21.0 |
||
Page: 21.0 |
minor | no (pharmacogenomic study) Comment: CYP3A5 genotype did not appear to impact gefitinib PK Page: 21.0 |
||
| yes |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| Inhibition of apoptosis by amphiregulin via an insulin-like growth factor-1 receptor-dependent pathway in non-small cell lung cancer cell lines. | 2002-12-20 |
|
| Despite concerns, FDA panel backs EGFR inhibitor. | 2002-11-06 |
|
| Second/third/fourth line therapy with tyrosine kinase inhibitors in NSCLC. | 2002-11-06 |
|
| Tyrosine kinase signal transduction inhibitors. Clinical trials. | 2002-11-06 |
|
| The rational basis of using novel targeted biological agents in non-small cell lung cancer. | 2002-11-06 |
|
| Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. | 2002-11-01 |
|
| The multifunctional, multi-institutional, and sometimes even global phase I study: a better life for phase I evaluations or just "living large"? | 2002-11-01 |
|
| Syntheses and EGFR and HER-2 kinase inhibitory activities of 4-anilinoquinoline-3-carbonitriles: analogues of three important 4-anilinoquinazolines currently undergoing clinical evaluation as therapeutic antitumor agents. | 2002-10-21 |
|
| Cancer drugs. Smart weapons prove tough to design. | 2002-10-18 |
|
| ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. | 2002-10-15 |
|
| Molecular characterization as a target for cancer therapy in relation to orphan status disorders (Review). | 2002-10-11 |
|
| Enhancement of antitumor activity of ionizing radiation by combined treatment with the selective epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 (Iressa). | 2002-10 |
|
| Surprise phase III failure for ZD1839. | 2002-10 |
|
| The role of EGFR-directed therapy in the treatment of breast cancer. | 2002-10 |
|
| Inhibition of epidermal growth factor receptor signaling in malignant pleural mesothelioma. | 2002-09-15 |
|
| Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trial. | 2002-09-15 |
|
| Gefitinib (Iressa) for advanced non-small cell lung cancer. | 2002-09-02 |
|
| Follicular and epidermal alterations in patients treated with ZD1839 (Iressa), an inhibitor of the epidermal growth factor receptor. | 2002-09 |
|
| Modulation of radiation response and tumor-induced angiogenesis after epidermal growth factor receptor inhibition by ZD1839 (Iressa). | 2002-08-01 |
|
| A serum factor after intestinal resection stimulates epidermal growth factor receptor signaling and proliferation in intestinal epithelial cells. | 2002-08 |
|
| [New therapeutic targets and strategies in lung cancer]. | 2002-08 |
|
| Epidermal growth factor receptor tyrosine kinase inhibitors. | 2002-08 |
|
| Selective inhibition of the epidermal growth factor receptor by ZD1839 decreases the growth and invasion of ovarian clear cell adenocarcinoma cells. | 2002-07 |
|
| Targeting epidermal growth factor receptor in lung cancer. | 2002-07 |
|
| The epidermal growth factor receptor: a new target for anticancer therapy. | 2002-06-27 |
|
| A sensitive assay for ZD1839 (Iressa) in human plasma by liquid-liquid extraction and high performance liquid chromatography with mass spectrometric detection: validation and use in Phase I clinical trials. | 2002-06-20 |
|
| Cancer medicine hits a target. | 2002-06-03 |
|
| Selective inhibition of the epidermal growth factor receptor impairs intestinal adaptation after small bowel resection. | 2002-06-01 |
|
| Gateways to Clinical Trials. June 2002. | 2002-06 |
|
| HER (erbB) tyrosine kinase inhibitors in the treatment of breast cancer. | 2002-06 |
|
| Molecular mechanisms in signal transduction: new targets for the therapy of gynecologic malignancies. | 2002-06 |
|
| Modulation of epidermal growth factor receptor in endocrine-resistant, estrogen-receptor-positive breast cancer. | 2002-06 |
|
| [Future trends in anticancer chemotherapy]. | 2002-05 |
|
| [Latest therapeutic strategy for stage IV non-small cell lung cancer]. | 2002-05 |
|
| [New treatment strategy for stage III non-small-cell lung cancer]. | 2002-05 |
|
| [ZD1839]. | 2002-05 |
|
| ZD1839 (IRESSA): a selective EGFR-TK inhibitor. | 2002-04 |
|
| HER-targeted tyrosine-kinase inhibitors. | 2002 |
|
| Gefitinib. | 2002 |
|
| Epidermal growth factor receptor dependence in human tumors: more than just expression? | 2002 |
|
| ZD1839 (Iressa): what's in it for the patient? | 2002 |
|
| ZD1839 (Iressa): for more than just non-small cell lung cancer. | 2002 |
|
| ZD1839 (Iressa) in non-small cell lung cancer. | 2002 |
|
| Why the epidermal growth factor receptor? The rationale for cancer therapy. | 2002 |
|
| Cytotoxic agents in the era of molecular targets and genomics. | 2002 |
|
| 93rd Annual Meeting of the American Association for Cancer Research, San Francisco, CA, USA, 6-10 April 2002. | 2002 |
|
| Finding the needle in the haystack: why high-throughput screening is good for your health. | 2002 |
|
| OSI Pharmaceuticals, Genentech and Roche announce data from clinical studies of Tarceva. | 2001-06 |
|
| New drug targets for genomic cancer therapy: successes, limitations, opportunities and future challenges. | 2001-05 |
|
| New drugs in gynecologic cancer. | 2001-04 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/gefitinib.html
250 mg orally once a day
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24740895
Gefitinib could inhibit highly expressed EGFR cell growth in a dose-dependent manner in the range of dose from 0.10 to 102.4 uM
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 18:06:07 GMT 2025
by
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on
Mon Mar 31 18:06:07 GMT 2025
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| Record UNII |
S65743JHBS
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Validated (UNII)
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EU-Orphan Drug |
EU/3/18/2075
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WHO-ATC |
L01XE02
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NCI_THESAURUS |
C129825
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WHO-VATC |
QL01XE02
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EMA ASSESSMENT REPORTS |
IRESSA (AUTHORIZED: CARCINOMA, NON-SMALL-CELL LUNG)
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NDF-RT |
N0000175605
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NDF-RT |
N0000175076
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NCI_THESAURUS |
C1967
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FDA ORPHAN DRUG |
443014
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LIVERTOX |
NBK548839
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100000091738
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GEFITINIB
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CHEMBL939
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S65743JHBS
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SUB20637
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DB00317
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DTXSID8041034
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S65743JHBS
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m5682
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C419708
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4941
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49668
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NN-73
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184475-35-2
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759856
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123631
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1282
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Gefitinib
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| Related Record | Type | Details | ||
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TRANSPORTER -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR | |||
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OFF TARGET->NON-INHIBITOR |
Overall survival (OS) was significantly shorter among patients with uncommon EGFR mutations (G719X or L861Q) com-pared with OS of those with common EGFR mutations (12 versus 28.4 months; p = 0.002). In the gefitinib group (n = 114), patients with uncommon EGFR mutations had a significantly shorter OS (11.9 versus 29.3 months; p < 0.001). By contrast, OS was similar between patients with uncommon mutations and those with common mutations in the carboplatin-paclitaxel group (n = 111; 22.8 versus 28 months; p = 0.358)
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TRANSPORTER -> INHIBITOR | |||
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BINDER->LIGAND |
In vitro binding of gefitinib to human plasma proteins (serum albumin and ?1-acid glycoprotein) is 90% and is independent of drug concentrations.
BINDING
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TARGET -> INHIBITOR |
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TRANSPORTER -> SUBSTRATE | |||
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TRANSPORTER -> INDUCER | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> SUBSTRATE | |||
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METABOLIC ENZYME -> INHIBITOR |
Ki
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METABOLITE -> PARENT |
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ACTIVE MOIETY |
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| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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| Tmax | PHARMACOKINETIC |
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ORAL ADMINISTRATION |
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| Biological Half-life | PHARMACOKINETIC |
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| Volume of Distribution | PHARMACOKINETIC |
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| ORAL BIOAVAILABILITY | PHARMACOKINETIC |
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