U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C21H23N7O2S
Molecular Weight 437.5199
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PAZOPANIB

SMILES

Cc1ccc(cc1S(=O)(=O)N)Nc2nccc(n2)N(C)c3ccc4c(C)n(C)nc4c3

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)

HIDE SMILES / InChI

Molecular Formula C21H23N7O2S
Molecular Weight 437.5199
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.14 µM [IC50]
0.13 µM [IC50]
0.146 µM [IC50]
0.071 µM [IC50]
0.084 µM [IC50]
0.074 µM [IC50]
0.43 µM [IC50]
0.411 µM [IC50]
0.01 µM [IC50]
0.03 µM [IC50]
0.047 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
VOTRIENT

Approved Use

VOTRIENT® 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 Date

1.25591041E12
Primary
VOTRIENT

Approved Use

VOTRIENT® 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 Date

1.25591041E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
44.8 mg/L
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
821 mg × h/L
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
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

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
PAZOPANIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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...
AEs leading to
discontinuation/dose reduction:
Proteinuria (5 patients)
Sources: Page: p. 61
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)
AST 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)
Sources: Page: p. 61
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)
Aspartate aminotransferase increased (grade 2, 1 patient)
Hyperbilirubinemia (grade 2, 1 patient)
Other AEs:
Diarrhea (all grades, 50%)
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%)
Sources:
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)
Malaise (grade 3, 2 patients)
ALT increased (grade 3, 2 patients)
Sources:
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
unhealthy
n = 3
DLT: Fatigue...
1000 mg 1 times / day multiple, oral
unhealthy
n = 3
DLT: Hypertension...
AEs

AEs

AESignificanceDosePopulation
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
unhealthy
n = 3
Hypertension grade 3, 1 patient
DLT, Disc. AE
1000 mg 1 times / day multiple, oral
unhealthy
n = 3
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
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%;
Page: 32.0
moderate [IC50 11 uM]
no (co-administration study)
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%;
Page: 33,37
moderate [IC50 15 uM]
moderate [IC50 16 uM]
no (co-administration study)
moderate [IC50 17 uM]
moderate [IC50 18 uM]
yes (co-administration study)
Comment: increased the AUC of CYP2D6 substrate (dextromethorphan) by 64%
Page: 32,37
moderate [IC50 7.9 uM]
no (co-administration study)
moderate
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%;
Page: 32,33,37
no
no
yes [IC50 0.79 uM]
yes [IC50 1.2 uM]
yes (pharmacogenomic study)
Comment: Certain UGT1A1 genotypes are associated with an increase in the risk of pazopanib induced hyperbilirubinemia.
Page: 34,4
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
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;
Page: 32,35
minor
minor
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;
Page: 34,35
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
New treatment approaches in metastatic renal cell carcinoma.
2006 Sep
Role of anti-angiogenesis agents in treating NSCLC: focus on bevacizumab and VEGFR tyrosine kinase inhibitors.
2007 Feb
Recent advances in the therapy of renal cancer.
2007 Feb
[Angiogenesis and renal cell carcinoma].
2007 Jul
Neovascular age-related macular degeneration: potential therapies.
2008
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
[Systemic therapy of metastasizing renal cell carcinoma].
2008 Oct
Anti-VEGF therapy as adjuvant therapy: clouds on the horizon?
2009
Suppression and regression of choroidal neovascularization by the multitargeted kinase inhibitor pazopanib.
2009 Apr
Response to antiangiogenesis therapy in a patient with advanced adult-type testicular granulosa cell tumor.
2009 Aug
Major clinical research advances in gynecologic cancer 2009.
2009 Dec
Impact of anti-angiogenic treatments on metastatic renal cell carcinoma.
2009 Dec
Vascular endothelial growth factor-targeted therapy in metastatic renal cell carcinoma.
2009 May 15
Vascular endothelial growth factor inhibition is not an effective therapeutic strategy for relapsed or refractory multiple myeloma: a phase 2 study of pazopanib (GW786034).
2009 May 7
Myelosuppression and kinase selectivity of multikinase angiogenesis inhibitors.
2009 Nov 17
VEGFR1 activity modulates myeloid cell infiltration in growing lung metastases but is not required for spontaneous metastasis formation.
2009 Sep 18
Targeting angiogenesis with multitargeted tyrosine kinase inhibitors in the treatment of non-small cell lung cancer.
2010
A current review of targeted therapeutics for ovarian cancer.
2010
Prognostic stratification of patients with advanced renal cell carcinoma treated with sunitinib: comparison with the Memorial Sloan-Kettering prognostic factors model.
2010 Feb 18
[Antiangionic drugs in soft tissue sarcoma].
2010 Jun
Patents

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
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 Fri Jun 25 22:05:04 UTC 2021
Edited
by admin
on Fri Jun 25 22:05:04 UTC 2021
Record UNII
7RN5DR86CK
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PAZOPANIB
DASH   EMA EPAR   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
PAZOPANIB [WHO-DD]
Common Name English
PAZOPANIB [VANDF]
Common Name English
PAZOPANIB [EMA EPAR]
Common Name English
5-((4-((2,3-DIMETHYL-2H-INDAZOL-6-YL)(METHYL)AMINO)PYRIMIDIN-2-YL)AMINO)-2-METHYLBENZENESULFONAMIDE
Systematic Name English
GW786034
Code English
PAZOPANIB [INN]
Common Name English
PAZOPANIB [MI]
Common Name English
BENZENESULFONAMIDE, 5-((4-((2,3-DIMETHYL-2H-INDAZOL-6-YL)METHYLAMINO)-2-PYRIMIDINYL)AMINO)-2-METHYL-
Systematic Name English
NSC-752782
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 705819
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
NCI_THESAURUS C1967
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
EMA ASSESSMENT REPORTS VOTRIENT (AUTHORIZED: CARCINOMA, RENAL CELL)
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
WHO-ATC L01XE11
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
FDA ORPHAN DRUG 383912
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
WHO-VATC QL01XE11
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
LIVERTOX 742
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
NCI_THESAURUS C1742
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
NDF-RT N0000175605
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
FDA ORPHAN DRUG 293809
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
Code System Code Type Description
EVMPD
SUB29175
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY
ChEMBL
CHEMBL477772
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY
PUBCHEM
10113978
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY
NDF-RT
N0000182137
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY Cytochrome P450 2D6 Inhibitors [MoA]
HSDB
8210
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY
WIKIPEDIA
PAZOPANIB
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY
MESH
C516667
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY
DRUG CENTRAL
4118
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY
NDF-RT
N0000182141
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
NDF-RT
N0000187062
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY Cytochrome P450 2C8 Inhibitors [MoA]
RXCUI
714438
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY RxNorm
CAS
444731-52-6
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY
EPA CompTox
444731-52-6
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY
MERCK INDEX
M8430
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY Merck Index
LACTMED
Pazopanib
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY
FDA UNII
7RN5DR86CK
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY
DRUG BANK
DB06589
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY
INN
8681
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY
IUPHAR
5698
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY
NCI_THESAURUS
C74547
Created by admin on Fri Jun 25 22:05:04 UTC 2021 , Edited by admin on Fri Jun 25 22:05:04 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
TRANSPORTER -> SUBSTRATE
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