Table 3.
The characteristics of the kinetics of cabozantinib oxidation by CYP3A4 and this enzyme in the presence of cyt b5.
| Enzyme | Metabolite | Kinetic Characteristics a | ||
|---|---|---|---|---|
| VMax (peak area/min/nmol CYP) | K0.5 (μM) | Ki (μM) | ||
| CYP3A4 | Monohydroxy cabozantinib | 1.50 ± 0.05 | 8.98 ± 1.04 | 947.87 ± 202.96 |
| Desmethyl cabozantinib | 1.44 ± 0.03 | 11.69 ± 1.00 | NA | |
| Cabozantinib N-oxide | 1.54 ± 0.04 | 9.56 ± 0.69 | NA | |
| CYP3A4 + cyt b5 | Monohydroxy cabozantinib | 3.60 ± 0.11 | 26.00 ± 2.92 | NA |
| Desmethyl cabozantinib | 5.70 ± 0.24 | 38.53 ± 5.35 | NA | |
| Cabozantinib N-oxide | 9.96 ± 0.92 | 32.03 ± 5.68 | 490.22 ± 139.7 | |
a Values represent means ± SD of three independent in vitro incubations (n = 3). NA—not applicable.