21.3.4 Vandetanib

Vandetanib is a quinazoline-based small molecule EGFR inhibitors. It was approved

by the FDA in 2011 for the treatment of medullary thyroid cancer. The chemical

structure of the drug is given in Fig. 21.2. The drug is administered through oral

route and the peak plasma concentration is achieved after 6 h of ingestion. The

volume of distribution of the drug is about 7450 L. The drug attains the protein

binding of about 90% after reaching to systemic circulation. The drug is metabolized

by the hepatic enzyme CYP3A4 and FMO1/3 into N-desmethyl vandetanib and

vandetanib N-oxide, respectively. About 44% of the drug is eliminated via faeces

and 25% via urine (Karras et al. 2014).

21.3.5 Afatinib

Afatinib is a quinazoline-based small molecule EGFR inhibitor. It was approved by

the FDA in 2013 for the treatment of NSCLC. The chemical structure of the drug is

given in Fig. 21.2. The drug acts by binding irreversibly or covalently with the

catalytic domain of the receptor. The drug is administered through oral route and

reaches to peak plasma concentration after 2–5 h of administration. The volume of

distribution of the drug is 4500 L. The drug attains the protein binding of about 95%

after reaching to systemic circulation. The drug is metabolized by the enzyme-

catalysed process to a negligible extent, and the major circulating enzymes are the

covalent adducts. About 86% of the drug is eliminated via faeces and 5% via urine

(Wecker and Waller 2018).

21.3.6 Dacomitinib

Dacomitinib is a quinazoline-based small molecule EGFR inhibitor. It was approved

by the FDA in 2018 for the treatment of EGFR-mutated NSCLC. The chemical

structure of the drug is given in Fig. 21.2. The drug acts by binding covalently to the

catalytic domain of the kinases. It is the selective and irreversible inhibitor of EGFR.

The drug is administered through oral route and reaches to peak plasma concentra-

tion after 5–6 h of administration. The volume of distribution of the drug is 2415 L.

The drug attains the protein binding of about 98% after reaching to systemic

circulation. The drug is metabolized by the enzyme-catalysed process to a negligible

extent, and the major circulating enzymes are the covalent adducts. About 79% of

the drug is eliminated via faeces and 3% via urine (Shirley 2018).

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