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. |
