|Systematic (IUPAC) name|
|Licence data||US FDA:|
|Metabolism||CYP3A4, FMO1, FMO3|
|Half-life||19 days (mean)|
|Excretion||44% faeces, 25% urine|
|Mol. mass||475.354 g/mol|
|(what is this?)|
Vandetanib (INN, trade name Caprelsa) is an anti-cancer drug that is used for the treatment of certain tumours of the thyroid gland. It acts as a kinase inhibitor of a number of cell receptors, mainly the vascular endothelial growth factor receptor (VEGFR), the epidermal growth factor receptor (EGFR), and the RET-tyrosine kinase. The drug was developed by AstraZeneca.
Approvals and indications
Vandetanib was the first drug to be approved by FDA (April 2011) for treatment of late-stage (metastatic) medullary thyroid cancer in adult patients who are ineligible for surgery. Vandetanib was first initially marketed without a trade name, and is being marketed under the trade name Caprelsa since August 2011.
In patients with moderate and severe hepatic impairment, no dosage for vandetanib has been recommended, as its safety and efficacy has not been established yet. Vandetanib is contraindicated in patients with congenital long QT syndrome.
Vandetanib has been reported as a substrate for the OATP-1B1 and OATP-1B3 transporter. Interaction of vandetanib with OATP-1B1 and OATP-1B3 may alter its hepatic disposition and can lead to transporter mediated drug-drug interactions. Also, Vandetanib is an inhibitor of OATP-1B3 transporter but not for OATP-1B1.
Other drugs that prolong the QT interval can possibly add to this side effect of vandetanib. As the drug is partly metabolised via the liver enzyme CYP3A4, strong inducers of this enzyme can decrease its blood plasma concentrations. CYP3A4 inhibitors do not significantly increase vandetanib concentrations, presumably because it is also metabolised by flavin containing monooxygenase 1 (FMO1) and 3.
Vandetanib is well absorbed from the gut, reaches peak blood plasma concentrations 4 to 10 hours after application, and has a half-life of 19 days on average. It has to be taken for about three months to achieve a steady-state concentration. In the blood, it is almost completely (90–96%) bound to plasma proteins such as albumin. It is metabolised to N-desmethylvandetanib via CYP3A4 and to vandetanib-N-oxide via FMO1 and 3. Both of these are active metabolites. Vandetanib is excreted via the faeces (44%) and the urine (25%) in form of the unchanged drug and the metabolites.
Non-small cell lung cancer
The drug underwent clinical trials as a potential targeted treatment for non-small-cell lung cancer. There have been some promising results from a phase III trial with docetaxel. There have also been ambivalent results when used with pemetrexed. Another trial with docetaxel was recruiting in July 2009.
AstraZeneca withdrew EU regulatory submissions for vandetanib (under the proposed trade name Zactima) in October 2009 after trials showed no benefit when the drug was administered alongside chemotherapy.
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