Table 2.
Mean radioactivity distribution of [14C]tinengotinib and its metabolites in plasma, urine, and feces
| Metabolites | Modification | Plasma | Urine | Feces | Feces + urine | |
|---|---|---|---|---|---|---|
| %AUC | M/P (%)a | %Dose | %Dose | %Dose | ||
| Tinengotinib | Parent compound | 88.23 | NA | 0.28 | 68.65 | 68.93 |
| M602 | Glucuronidation of M426-2 | ND | NA | 0.19 | ND | 0.19 |
| M588-1 | Glucuronidation of M412-1 (TT-00925) | ND | NA | 0.24 | ND | 0.24 |
| M588-2 | Glucuronidation of M412-2 (TT-00890) | ND | NA | 0.65 | ND | 0.65 |
| M410-1 | Mono-oxidation | ND | NA | 0.43 | 1.76 | 2.19 |
| M382 | Oxidation and de-ethylation of morpholine ring to carboxylic acid | ND | NA | 0.37 | 1.23 | 1.60 |
| M412-1 (TT-00925) | Oxidative cleavage of morpholine ring | 0.06 | 0.07 | 0.19 | 2.72 | 2.91 |
| M426-2 | Di-oxidation | ND | NA | 0.38 | 5.10 | 5.48 |
| M412-2 (TT-00890) | Oxidative cleavage of morpholine ring | 0.06 | 0.07 | 0.31 | 3.14 | 3.45 |
| M410-3 (TT-02236) | Mono-oxidation | 4.75 | 5.38 | 0.46 | 3.00 | 3.46 |
| M570-1 | Glucuronide conjugation | 2.54 | 2.88 | 1.82 | 1.60 | 3.42 |
| M513 | Cysteine conjugation | ND | NA | ND | 0.84 | 0.84 |
| Total of identified radioactivityb | 95.64 | 5.32 | 88.04 | 93.36 | ||
| Total of unidentified radioactivityc | 3.09 | 1.82 | 4.45 | 6.27 | ||
| Percentage of identified radioactivityd | 95.64 | 74.82 | 95.22 | 93.76 | ||
ND not detected, NA not applicable
aRatio of metabolites to parent compound in plasma
bRatio of peak area of identified radioactive peak to total plasma radioactive exposure or to dose administered
cPeak area of a single radioactive peak did not exceed 1.50% AUC, or 5.00% dose
dProportion of identified radioactive peaks in current matrix