vandetanib

Ligand id: 5717

Name: vandetanib

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 59.51
Molecular weight 474.11
XLogP 4.17
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
Used in the treatment of thyroid cancer.
Mechanism Of Action and Pharmacodynamic Effects
VEGFR- and EGFR-dependent signalling pathways have been shown to be involved in some types of cancer, including non-small-cell lung cancer (NSCLC) and RET activity is important in some types of thyroid cancer. Vandetanib potently inhibits VEGFR-2, EGFR and RET tyrosine kinases. It is also a sub-micromolar inhibitor of VEGFR-3 tyrosine kinase.
Pharmacokinetics
Absorption/Distribution
Vandatenib is absorbed slowly, taking 4-10h to reach peak plasma concentration. Protein binding (albumin and α-1 acid glycoprotein) is approximately 90%. Volume of distributuion is >7L suggesting extensive distribution from the plasma into tissues.
Biotransformation/Metabolism
CYP3A4 metabilizes vandatenib to N-desmethyl-vandetanib and the flavin-containing monooxygenase enzymes (FMO1 and FMO3) convert the parent drug to vandetanib-N-oxide. Unchanged vandentanib and its metabolites can be detected in plasma, urine and feces.
Elimination
Vandatenib is eliminated primarily in the feces (44%) and the urine (25%).
Population pharmacokinetics
Pharmacokinetics of vandatenib are not significantly affected by age or gender. The pharmacokinetics have not been evaluated in children. Japanese and Chinese patients had, on average, exposures that were higher than in white patients receiving the same dose.
Organ function impairment
Hepatic impairment: A single dose pharmacokinetic study in volunteers indicated that hepatic impairment did not affect exposure to vandetanib. However, vanatenib treatment is not recommended for use in patients with moderate and severe hepatic impairment because safety and efficacy are not well established. Renal impairment: A single dose pharmacokinetic study in volunteers indicated that exposure to vandetanib is enhanced (up to 1.5, 1.6 and 2-fold) in mild, moderate and severe renal impaired subjects respectively, compared to subjects with normal renal function.
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