protein binding is 99,5% for both drugs. The drugs are mainly metabolized in the liver by oxidative metabolism of CYP3A4, and glucuronidized by UGT1A9. Their half life ranges from 20 to 48 hours. Most of the administered dose should be out of the system in around 14 days. The drugs are mostly excreted in faeces, around 70-80%, but also in urine. Pharmacokinetics of indoline derivatives Sunitinib's peak plasma level is reached 6–12 hours post-dose. The drug is 95% protein bound and has a volume of distribution of 2230 L, which indicates distribution into tissues. Sunitinib is metabolised mostly by CYP3A4 and has a half life of 40–60 hours. Nintedanib reaches maximum plasma concentration 2–4 hours post-dose. The drug is 97,8% protein bound and is preferentially distributed in plasma. Only a minor part of the biotransformation of nintedanib is caused by CYP3A4 as the prevalent metabolic reaction for nintedanib is a hydrolytic cleavage of esterases. The half-life of nintedanib is about 10–15 hours. Pharmacokinetics of pyridine derivatives Axitinib has short half-life, ranging from 2.5 to 6.1 hours, and therefore steady state should be reached in 2–3 days after the first dose. Peak plasma concentration is reached in 2.5 to 4.1 hours. In vitro protein binding is over 99%. Axitinib is primarily metabolized in the liver by CYP3A4/5. 30-60% of the drug is excreted in faeces, and about 23% in urine. Regorafenib is a pyridine derivative, but also a urea derivative and has therefore been covered in that section. Pharmacokinetics of pyrimidine derivatives Pazopanib reaches maximum plasma concentration 3.5 hours post-dose. Pazopanib is about 99% protein bound to human plasma protein. Metabolism of pazopanib is mediated primarily by CYP3A4 and the half-life of the drug is about 30.9 hours. Elimination of pazopanib is primarily with faeces. History Inhibition of angiogenesis including VEGFR-2 inhibitors has been of much interest and research in recent decades because angiogenesis is required for tumors to grow beyond a diameter of 1–2 mm. Many small molecular drugs and biological macromolecules targeting VEGFRs or blocking signal transduction of VEGF/VEGFR have been approved for clinical use or entered clinical trials. In 2004 the monoclonal antibody bevacizumab became the first VEGFR inhibitor to be approved for cancer therapy. The first small molecular VEGFR-2 inhibitor to be approved was sunitinib in 2006. References Tyrosine kinase inhibitors