Details
Stereochemistry | ACHIRAL |
Molecular Formula | C21H23N7O2S |
Molecular Weight | 437.518 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN(C1=CC2=NN(C)C(C)=C2C=C1)C3=CC=NC(NC4=CC=C(C)C(=C4)S(N)(=O)=O)=N3
InChI
InChIKey=CUIHSIWYWATEQL-UHFFFAOYSA-N
InChI=1S/C21H23N7O2S/c1-13-5-6-15(11-19(13)31(22,29)30)24-21-23-10-9-20(25-21)27(3)16-7-8-17-14(2)28(4)26-18(17)12-16/h5-12H,1-4H3,(H2,22,29,30)(H,23,24,25)
Molecular Formula | C21H23N7O2S |
Molecular Weight | 437.518 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment: Description was created based on several sources, including
http://adisinsight.springer.com/drugs/800016874 | https://www.ncbi.nlm.nih.gov/pubmed/26767042 | https://www.ncbi.nlm.nih.gov/pubmed/17620431
Curator's Comment: Description was created based on several sources, including
http://adisinsight.springer.com/drugs/800016874 | https://www.ncbi.nlm.nih.gov/pubmed/26767042 | https://www.ncbi.nlm.nih.gov/pubmed/17620431
Pazopanib (VOTRIENT) is an orally bioavailable multi-targeted tyrosine kinase receptor inhibitor. Pazopanib inhibits vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, platelet-derived growth factor receptor (PDGFR)-α and -β, fibroblast growth factor receptor (FGFR) -1 and -3, cytokine receptor (Kit), interleukin-2 receptor inducible T-cell kinase (Itk), leukocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c-Fms). In an vitro study, pazopanib exerted anti-tumor effect through mechanisms including the Raf-MAPK/ERK (MEK)-extracellular signal-regulated kinase (ERK) pathway. It has good oral exposure and inhibits angiogenesis and tumor growth in mice. Pazopanib (VOTRIENT) was developed by GlaxoSmithKline for the treatment of solid tumours and age-related macular degeneration. However, Novartis acquired all the rights to the drug from GlaxoSmithKline. Pazopanib (VOTRIENT) is indicated for the treatment of patients with advanced renal cell carcinoma and advanced soft tissue sarcoma.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3650 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/ |
0.14 µM [IC50] | ||
Target ID: CHEMBL2742 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/ |
0.13 µM [IC50] | ||
Target ID: CHEMBL1844 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/ |
0.146 µM [IC50] | ||
Target ID: CHEMBL2007 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/ |
0.071 µM [IC50] | ||
Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/ |
0.084 µM [IC50] | ||
Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/ |
0.074 µM [IC50] | ||
Target ID: CHEMBL2959 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/ |
0.43 µM [IC50] | ||
Target ID: CHEMBL258 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/ |
0.411 µM [IC50] | ||
Target ID: CHEMBL1868 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/ |
0.01 µM [IC50] | ||
Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/ |
0.03 µM [IC50] | ||
Target ID: CHEMBL1955 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17620431/ |
0.047 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | VOTRIENT Approved UseVOTRIENT® is indicated for the treatment of patients with advanced renal cell carcinoma (RCC). VOTRIENT is indicated for the treatment of patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy. Limitation of Use: The efficacy of VOTRIENT for the treatment of patients with adipocytic STS or gastrointestinal stromal tumors has not been demonstrated. VOTRIENT is a kinase inhibitor indicated for the treatment of patients with: •advanced renal cell carcinoma. (1) •advanced soft tissue sarcoma who have received prior chemotherapy. (1) Limitation of Use: The efficacy of VOTRIENT for the treatment of patients with adipocytic soft tissue sarcoma or gastrointestinal stromal tumors has not been demonstrated. Launch Date2009 |
|||
Primary | VOTRIENT Approved UseVOTRIENT® is indicated for the treatment of patients with advanced renal cell carcinoma (RCC). VOTRIENT is indicated for the treatment of patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy. Limitation of Use: The efficacy of VOTRIENT for the treatment of patients with adipocytic STS or gastrointestinal stromal tumors has not been demonstrated. VOTRIENT is a kinase inhibitor indicated for the treatment of patients with: •advanced renal cell carcinoma. (1) •advanced soft tissue sarcoma who have received prior chemotherapy. (1) Limitation of Use: The efficacy of VOTRIENT for the treatment of patients with adipocytic soft tissue sarcoma or gastrointestinal stromal tumors has not been demonstrated. Launch Date2009 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
44.8 mg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31125423 |
800 mg 1 times / day multiple, oral dose: 800 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
PAZOPANIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
50.2 mg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31125423 |
600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
PAZOPANIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
58.1 μg/mL |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
PAZOPANIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
821 mg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31125423 |
800 mg 1 times / day multiple, oral dose: 800 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
PAZOPANIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
895 mg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31125423 |
600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
PAZOPANIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
1037 μg × h/mL |
800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered: |
PAZOPANIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1% |
PAZOPANIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Disc. AE: Proteinuria... |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Disc. AE: ALT increased, AST increased... AEs leading to discontinuation/dose reduction: ALT increased (11 patient) Sources: Page: p. 61AST increased (11 patient) Bilirubin increased (11 patient) Myocardial infarction (6 patients) Ischemic stroke (6 patients) Transient ischemic attack (6 patients) Fatigue (5 patients) Diarrhea (7 patients) Anorexia (7 patients) Vomiting (7 patients) Proteinuria (3 patients) Hypertension (2 patients) Hemorrhage (2 patients) Confusion (12 patients) Infection (12 patients) Hand-and-foot syndrome (12 patients) Edema (12 patients) Dehydration (12 patients) Anemia (12 patients) Anxiety (12 patients) Convulsion (12 patients) Atrial fibrillation (12 patients) Hypertension (20 patients) Gastrointestinal disturbance (17 patients) Liver function test abnormal (16 patients) Fatigue (10 patients) Hematologic disorder (4 patients) Rash (5 patients) |
600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
DLT: Neutropenia, Aspartate aminotransferase increased... Other AEs: Diarrhea, Hypertension... Dose limiting toxicities: Neutropenia (grade 2, 1 patient) Other AEs:Aspartate aminotransferase increased (grade 2, 1 patient) Hyperbilirubinemia (grade 2, 1 patient) Diarrhea (all grades, 50%) Sources: Hypertension (grade 3, 13%) AST increased (grade 3, 13%) ALT increased (all grades, 25%) Cough (all grades, 13%) Skin hypopigmentation (all grades, 50%) Weight decrease (all grades, 25%) Alopecia (all grades, 13%) Dizziness (all grades, 13%) Hyperbilirubinemia (all grades, 25%) Abdominal distension (all grades, 25%) Abdominal pain (all grades, 25%) Fatigue (all grades, 13%) Leukopenia (all grades, 13%) Muscle spasms (all grades, 25%) Upper respiratory tract infection (all grades, 13%) Hypercholesterolemia (grade 3, 13%) Gastrointestinal hemorrhage (grade 4, 13%) Hypoglycemia (grade 4, 13%) Transaminases increased (grade 4, 13%) |
800 mg 1 times / day multiple, oral Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 5 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 5 Sources: |
DLT: Aspartate aminotransferase increase, Malaise... Dose limiting toxicities: Aspartate aminotransferase increase (grade 3, 2 patients) Sources: Malaise (grade 3, 2 patients) ALT increased (grade 3, 2 patients) |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Condition: advanced renal cell carcinoma Age Group: adult Sources: |
Other AEs: Hepatotoxicity... Other AEs: Hepatotoxicity (severe|grade 5) Sources: |
2000 mg 1 times / day multiple, oral Highest studied dose Dose: 2000 mg, 1 times / day Route: oral Route: multiple Dose: 2000 mg, 1 times / day Sources: |
unhealthy n = 3 Health Status: unhealthy Population Size: 3 Sources: |
DLT: Fatigue... Dose limiting toxicities: Fatigue (grade 3, 1 patient) Sources: |
1000 mg 1 times / day multiple, oral Dose: 1000 mg, 1 times / day Route: oral Route: multiple Dose: 1000 mg, 1 times / day Sources: |
unhealthy n = 3 Health Status: unhealthy Population Size: 3 Sources: |
DLT: Hypertension... Dose limiting toxicities: Hypertension (grade 3, 1 patient) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Proteinuria | 5 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Fatigue | 10 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
ALT increased | 11 patient Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
AST increased | 11 patient Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Bilirubin increased | 11 patient Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Anemia | 12 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Anxiety | 12 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Atrial fibrillation | 12 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Confusion | 12 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Convulsion | 12 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Dehydration | 12 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Edema | 12 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Hand-and-foot syndrome | 12 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Infection | 12 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Liver function test abnormal | 16 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Gastrointestinal disturbance | 17 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Hemorrhage | 2 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Hypertension | 2 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Hypertension | 20 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Proteinuria | 3 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Hematologic disorder | 4 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Fatigue | 5 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Rash | 5 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Ischemic stroke | 6 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Myocardial infarction | 6 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Transient ischemic attack | 6 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Anorexia | 7 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Diarrhea | 7 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Vomiting | 7 patients Disc. AE |
800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: Page: p. 61 |
unhealthy, 59 years n = 290 Health Status: unhealthy Condition: renal cell carcinoma Age Group: 59 years Sex: M+F Population Size: 290 Sources: Page: p. 61 |
Alopecia | all grades, 13% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Cough | all grades, 13% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Dizziness | all grades, 13% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Fatigue | all grades, 13% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Leukopenia | all grades, 13% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Upper respiratory tract infection | all grades, 13% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
ALT increased | all grades, 25% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Abdominal distension | all grades, 25% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Abdominal pain | all grades, 25% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Hyperbilirubinemia | all grades, 25% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Muscle spasms | all grades, 25% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Weight decrease | all grades, 25% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Diarrhea | all grades, 50% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Skin hypopigmentation | all grades, 50% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Aspartate aminotransferase increased | grade 2, 1 patient DLT |
600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Hyperbilirubinemia | grade 2, 1 patient DLT |
600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Neutropenia | grade 2, 1 patient DLT |
600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
AST increased | grade 3, 13% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Hypercholesterolemia | grade 3, 13% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Hypertension | grade 3, 13% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Gastrointestinal hemorrhage | grade 4, 13% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Hypoglycemia | grade 4, 13% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
Transaminases increased | grade 4, 13% | 600 mg 1 times / day multiple, oral MTD Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 8 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 8 Sources: |
ALT increased | grade 3, 2 patients DLT |
800 mg 1 times / day multiple, oral Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 5 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 5 Sources: |
Aspartate aminotransferase increase | grade 3, 2 patients DLT |
800 mg 1 times / day multiple, oral Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 5 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 5 Sources: |
Malaise | grade 3, 2 patients DLT |
800 mg 1 times / day multiple, oral Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: |
unhealthy, 61 years (range: 38–76 years) n = 5 Health Status: unhealthy Condition: Hepatocellular Carcinoma Age Group: 61 years (range: 38–76 years) Sex: M+F Population Size: 5 Sources: |
Hepatotoxicity | severe|grade 5 | 800 mg 1 times / day multiple, oral Recommended Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Condition: advanced renal cell carcinoma Age Group: adult Sources: |
Fatigue | grade 3, 1 patient DLT, Disc. AE |
2000 mg 1 times / day multiple, oral Highest studied dose Dose: 2000 mg, 1 times / day Route: oral Route: multiple Dose: 2000 mg, 1 times / day Sources: |
unhealthy n = 3 Health Status: unhealthy Population Size: 3 Sources: |
Hypertension | grade 3, 1 patient DLT, Disc. AE |
1000 mg 1 times / day multiple, oral Dose: 1000 mg, 1 times / day Route: oral Route: multiple Dose: 1000 mg, 1 times / day Sources: |
unhealthy n = 3 Health Status: unhealthy Population Size: 3 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32.0 |
moderate [IC50 10 uM] | weak (co-administration study) Comment: AUC of paclitaxel (CYP3A4 and CYP2C8 substrate) increased by 26%, decreased paclitaxel clearance by 14%, and increased paclitaxel Cmax by 31%; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,36 |
moderate [IC50 11 uM] | no (co-administration study) Comment: no effect Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,36 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=33 Page: 33,37 |
moderate [IC50 11 uM] | weak (co-administration study) Comment: pazopanib increased the AUC of CYP3A4 substrate (midazolam) by 32%; AUC of paclitaxel (CYP3A4 and CYP2C8 substrate) increased by 26%, decreased paclitaxel clearance by 14%, and increased paclitaxel Cmax by 31%; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=33 Page: 33,37 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32.0 |
moderate [IC50 15 uM] | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,36 |
moderate [IC50 16 uM] | no (co-administration study) Comment: no effect Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,36 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32.0 |
moderate [IC50 17 uM] | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,37 |
moderate [IC50 18 uM] | yes (co-administration study) Comment: increased the AUC of CYP2D6 substrate (dextromethorphan) by 64% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,37 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,36 |
moderate [IC50 7.9 uM] | no (co-administration study) Comment: no effect Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,36 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,33 |
moderate | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,33,37 |
moderate | weak (co-administration study) Comment: pazopanib increased the AUC of CYP3A4 substrate (midazolam) by 32%; AUC of paclitaxel (CYP3A4 and CYP2C8 substrate) increased by 26%, decreased paclitaxel clearance by 14%, and increased paclitaxel Cmax by 31%; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,33,37 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=33 Page: 33.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=34 Page: 34.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=34 Page: 34.0 |
yes [IC50 0.79 uM] | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=34 Page: 34,4 |
yes [IC50 1.2 uM] | yes (pharmacogenomic study) Comment: Certain UGT1A1 genotypes are associated with an increase in the risk of pazopanib induced hyperbilirubinemia. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=34 Page: 34,4 |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,35 |
major | yes (co-administration study) Comment: pazopanib AUC (0-t), Cmax, and half-life were increased 1.47, 2.21, and 2.81 fold, respectively; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32,35 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32.0 |
minor | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=32 Page: 32.0 |
minor | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=34 Page: 34,35 |
yes | yes (co-administration study) Comment: AUC(0-t) and Cmax values of pazopanib are increased by 59 and 50%, respectively, when coadministered with lapatinib; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_ClinPharmR.pdf#page=34 Page: 34,35 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 68.0 |
PubMed
Title | Date | PubMed |
---|---|---|
[Angiogenesis targeting in breast cancer]. | 2007 |
|
[Angiogenesis and renal cell carcinoma]. | 2007 Jul |
|
Evolving role of novel targeted agents in renal cell carcinoma. | 2007 Sep |
|
Neovascular age-related macular degeneration: potential therapies. | 2008 |
|
Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor. | 2008 Aug 14 |
|
New drugs for ovarian cancer. | 2008 Feb |
|
Pazopanib, a potent orally administered small-molecule multitargeted tyrosine kinase inhibitor for renal cell carcinoma. | 2008 Feb |
|
HER-2 positive breast cancer: what else beyond trastuzumab-based therapy? | 2008 Jun |
|
Update on novel therapeutic agents for cervical cancer. | 2008 Sep |
|
Recent advances in systemic therapy: Advances in systemic therapy for HER2-positive metastatic breast cancer. | 2009 |
|
Emerging pharmacologic therapies for wet age-related macular degeneration. | 2009 |
|
Major clinical research advances in gynecologic cancer 2009. | 2009 Dec |
|
Impact of anti-angiogenic treatments on metastatic renal cell carcinoma. | 2009 Dec |
|
Pazopanib: therapeutic developments. | 2009 Dec |
|
Tyrosine kinase inhibitors and the thyroid. | 2009 Dec |
|
Synergistic proapoptotic effects of the two tyrosine kinase inhibitors pazopanib and lapatinib on multiple carcinoma cell lines. | 2009 Dec 3 |
|
Apical ballooning syndrome during treatment with a vascular endothelial growth factor receptor antagonist. | 2009 Jan 24 |
|
Tumoral angiogenesis and breast cancer. | 2009 Mar |
|
Vascular endothelial growth factor-targeted therapy in metastatic renal cell carcinoma. | 2009 May 15 |
|
Pazopanib: an antiangiogenic drug in perspective. | 2009 Nov |
|
New treatment approaches in renal cell carcinoma. | 2009 Nov |
|
Response to a novel multitargeted tyrosine kinase inhibitor pazopanib in metastatic Merkel cell carcinoma. | 2009 Sep 10 |
|
Targeting angiogenesis with multitargeted tyrosine kinase inhibitors in the treatment of non-small cell lung cancer. | 2010 |
|
Antiangiogenic therapy and mechanisms of tumor resistance in malignant glioma. | 2010 |
|
Everolimus (RAD001) in the treatment of advanced renal cell carcinoma: a review. | 2010 |
|
Anticancer Role of PPARgamma Agonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes. | 2010 |
|
Targeting signal transduction pathways in metastatic breast cancer: a comprehensive review. | 2010 |
|
A current review of targeted therapeutics for ovarian cancer. | 2010 |
|
Potent preclinical impact of metronomic low-dose oral topotecan combined with the antiangiogenic drug pazopanib for the treatment of ovarian cancer. | 2010 Apr |
|
Bridging the gap between cytotoxic and biologic therapy with metronomic topotecan and pazopanib in ovarian cancer. | 2010 Apr |
|
Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism. | 2010 Apr 27 |
|
Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02). | 2010 Aug |
|
Analytical control of process impurities in Pazopanib hydrochloride by impurity fate mapping. | 2010 Aug 1 |
|
Prognostic factors in patients treated with VEGF-targeted therapies. | 2010 Feb |
|
Angiogenesis inhibitors in the management of breast cancer. | 2010 Feb |
|
Molecular basis for the treatment of renal cell carcinoma. | 2010 Jan |
|
Pazopanib. | 2010 Jan |
|
New therapeutic strategies for renal cell carcinoma. | 2010 Jan-Feb |
|
[Antiangionic drugs in soft tissue sarcoma]. | 2010 Jun |
|
Pazopanib: an oral multitargeted tyrosine kinase inhibitor for use in renal cell carcinoma. | 2010 Jun |
|
Current status of vascular endothelial growth factor inhibition in age-related macular degeneration. | 2010 Jun |
|
Bevacizumab salvage therapy following progression in high-grade glioma patients treated with VEGF receptor tyrosine kinase inhibitors. | 2010 Jun |
|
Recent advances and future directions in the management of metastatic renal cell carcinoma. | 2010 Mar |
|
[Management of metastatic HER2-positive breast cancer: present and future]. | 2010 Mar |
|
Plasma cytokine and angiogenic factor profiling identifies markers associated with tumor shrinkage in early-stage non-small cell lung cancer patients treated with pazopanib. | 2010 Mar 15 |
|
Pazopanib: a multikinase inhibitor with activity in advanced renal cell carcinoma. | 2010 May |
|
Antitumor and antiangiogenic effect of the dual EGFR and HER-2 tyrosine kinase inhibitor lapatinib in a lung cancer model. | 2010 May 11 |
|
Growth factors in multiple myeloma: a comprehensive analysis of their expression in tumor cells and bone marrow environment using Affymetrix microarrays. | 2010 May 13 |
|
Everolimus and pazopanib: two new drugs for renal cell cancer. | 2010 May 3 |
|
Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. | 2010 May 5 |
Sample Use Guides
800 mg orally once daily without food (at least 1 hour before or 2 hours after a meal). Baseline moderate hepatic impairment – 200 mg orally once daily. Not recommended in patients with severe hepatic impairment.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25249557
Treatment of the KATO-III, OCUM-2M, SNU-16, and HSC-39 gastric cancer cell lines harboring FGFR2 amplification with pazopanib resulted in marked decreases of cell survival with IC50 in ranges of 0.1 to 2.0 uM, whereas the same treatment of those cell lines without FGFR2 amplification had no growth-inhibitory effects
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 15:59:10 GMT 2023
by
admin
on
Sat Dec 16 15:59:10 GMT 2023
|
Record UNII |
7RN5DR86CK
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Code | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
FDA ORPHAN DRUG |
705819
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
||
|
NCI_THESAURUS |
C1967
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
||
|
EMA ASSESSMENT REPORTS |
VOTRIENT (AUTHORIZED: CARCINOMA, RENAL CELL)
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
||
|
FDA ORPHAN DRUG |
383912
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
||
|
WHO-ATC |
L01XE11
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
||
|
WHO-VATC |
QL01XE11
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
||
|
LIVERTOX |
NBK548110
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
||
|
NCI_THESAURUS |
C1742
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
||
|
NDF-RT |
N0000175605
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
||
|
FDA ORPHAN DRUG |
293809
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
SUB29175
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
CHEMBL477772
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
10113978
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
N0000182137
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | Cytochrome P450 2D6 Inhibitors [MoA] | ||
|
8210
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
PAZOPANIB
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
C516667
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
4118
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
N0000182141
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | Cytochrome P450 3A4 Inhibitors [MoA] | ||
|
N0000187062
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | Cytochrome P450 2C8 Inhibitors [MoA] | ||
|
714438
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | RxNorm | ||
|
752782
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
444731-52-6
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
DTXSID8048733
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
m8430
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | Merck Index | ||
|
71219
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
Pazopanib
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
7RN5DR86CK
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
100000090733
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
7RN5DR86CK
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
DB06589
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
8681
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
5698
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY | |||
|
C74547
Created by
admin on Sat Dec 16 15:59:10 GMT 2023 , Edited by admin on Sat Dec 16 15:59:10 GMT 2023
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
TRANSPORTER -> SUBSTRATE | |||
|
SALT/SOLVATE -> PARENT |
|
||
|
TARGET -> INHIBITOR | |||
|
SALT/SOLVATE -> PARENT |
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
METABOLITE INACTIVE -> PARENT |
LESS THAN 10%
PLASMA
|
||
|
METABOLITE INACTIVE -> PARENT |
In plasma and blood,
individual circulating metabolites represented less than 10% total radioactivity
PLASMA
|
||
|
METABOLITE ACTIVE -> PARENT |
Only one of these metabolites (GSK1268997) has been shown to inhibit the proliferation of VEGF-stimulated human umbilical vein endothelial cells with potency similar to pazopanib. The other metabolites show at least 10- to 20-fold less activity than the parent compound in the same cellular assay.
|
||
|
METABOLITE INACTIVE -> PARENT |
FECAL
|
||
|
METABOLITE ACTIVE -> PARENT |
The majority of radiolabeled material recovered in feces constituted unchanged pazopanib,
accounting for a mean of 67% of the administered radioactivity activity dose. Pazopanib
metabolites GSK1268992 and GSK1268997 accounted for means of approximately 6% and
2% of the administered radioactivity dose, respectively.
FECAL
|
||
|
METABOLITE ACTIVE -> PARENT |
Renal elimination of pazopanib is accounted for less than 4% of bodily excretion of the
administered dose (Table 9). The majority of the radioactivity (82.2%) was recovered in
feces by 120 hours (Table 9). Pazopanib undergoes moderate liver metabolism.
FECAL; PLASMA; URINE
|
||
|
METABOLITE INACTIVE -> PARENT |
Four pazopanib metabolites (GSK1268992, GSK1268997, GSK1071306, and GW700201) have been identified. Only one of these metabolites (GSK1268997) has been shown to inhibit the proliferation of VEGF-stimulated human umbilical vein endothelial cells with potency similar to pazopanib. The other metabolites show at least 10- to 20-fold less activity than the parent compound in the same cellular assay.
|
||
|
METABOLITE INACTIVE -> PARENT |
Renal elimination of pazopanib is accounted for less than 4% of bodily excretion of the
administered dose (Table 9). The majority of the radioactivity (82.2%) was recovered in
feces by 120 hours (Table 9). Pazopanib undergoes moderate liver metabolism. Pazopanib
was the major drug-related component in human plasma representing 84% and 91% of the
AUC(0-∞) in two of the three subjects that received 400 mg radiolabeled pazopanib.
FECAL; PLASMA; URINE
|
||
|
METABOLITE INACTIVE -> PARENT |
Four pazopanib metabolites (GSK1268992, GSK1268997, GSK1071306, and GW700201) have been identified. Only one of these metabolites (GSK1268997) has been shown to inhibit the proliferation of VEGF-stimulated human umbilical vein endothelial cells with potency similar to pazopanib.
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
---|---|---|---|---|---|---|
Biological Half-life | PHARMACOKINETIC |
|
Elimination PHARMACOKINETIC |
|
||