Cabozantinib Pharmacokinetics
1. Absorption
(1) Absolute oral bioavailability has not been determined.
(2) After oral administration, the median time to peak plasma cabozantinib concentration ranges from 2 to 5 hours for cabozantinib capsules (Cometriq) and 3 to 4 hours for cabozantinib tablets (Cabometyx).
(3) Following a single 140 mg dose of cabozantinib capsules or tablets, the peak plasma concentration of the tablet is 19% higher than that of the capsule; however, the AUC difference between tablet and capsule is less than 10%.
(4) Steady-state concentrations are achieved after 15 days of dosing with cabozantinib capsules (Cometriq).
(5) Food effect: Compared with fasting conditions, administration of a 140 mg dose with a high-fat meal increased the peak concentration and AUC of cabozantinib capsules (Cometriq) by 41% and 57%, respectively.
(6) Special populations: Population pharmacokinetic analysis showed no clinically important differences in cabozantinib exposure between patients with normal hepatic function and those with mild hepatic impairment. In a dedicated pharmacokinetic study, cabozantinib exposure was increased by 63% in patients with moderate hepatic impairment. Severe hepatic impairment has not been studied. Systemic exposure of cabozantinib tablets (Cabometyx) at the recommended dose in pediatric patients ≥12 years of age is expected to be comparable to that in adults receiving a daily dose of 60 mg.
2. Distribution
(1) Extent: It is unknown whether cabozantinib or its metabolites distribute into human milk.
(2) Plasma protein binding: ≥99.7%.
3. Elimination
(1) Metabolism: Metabolized in the liver by CYP3A4; it is a substrate of CYP3A4 in vitro.
(2) Elimination routes: Excreted via feces (54%) and urine (27%).
(3) Half-life: Cometriq: approximately 55 hours. Cabometyx: approximately 99 hours.
(4) Special populations: Formal pharmacokinetic studies have not been conducted in patients with renal impairment worse than moderate.
4. Stability
Cabozantinib capsules (Cometriq): 20–25°C (excursions permitted between 15–30°C).
Cabozantinib tablets (Cabometyx): 20–25°C (excursions permitted between 15–30°C).
