TABLE 2
Proposed structures of [14C]apixaban metabolites and tissue occurrence
Drug or Metabolitea | Proposed Structureb | Source |
|---|---|---|
| Apixaban |
| Rat: plasma, urine, feces, bile, RH |
| Mouse: plasma, urine, feces, MH | ||
| Rabbit: plasma, urine, feces | ||
| Dog: plasma, urine, feces, DH | ||
| Monkey: MKH | ||
| Human: plasma, urine, feces, bile, HH | ||
| M1 (O-demethyl apixaban sulfate) |
| Rat: plasma, urine, bile, RH |
| Mouse: urine | ||
| Rabbit: plasma, urine, feces | ||
| Dog: plasma, urine | ||
| Monkey: MKH | ||
| Human: plasma, urine, feces, bile, HH | ||
| M2 (O-demethyl apixaban) |
| Rat: plasma, urine, feces, bile, RH |
| Mouse: plasma, urine, feces, MH | ||
| Rabbit: plasma, urine, feces | ||
| Dog: plasma, urine, feces, DH | ||
| Monkey: MKH | ||
| Human: feces, bile, HH | ||
| M3c (lactam ring-opened apixaban) |
| Rat: Bile, RH |
| Mouse: MH | ||
| Rabbit: N.D. | ||
| Dog: urine, feces, DH | ||
| Monkey: MKH | ||
| Human: HH | ||
| M4 (hydroxy apixaban) |
| Rat: plasma, urine, feces, bile, RH |
| Mouse: urine, feces, MH | ||
| Rabbit: feces | ||
| Dog: urine, feces, DH | ||
| Monkey: MKH | ||
| Human: feces, HH | ||
| M5c (lactam ring-opened apixaban) |
| Rat: N.D. |
| Mouse: MH | ||
| Rabbit: N.D. | ||
| Dog: DH | ||
| Monkey: MKH | ||
| Human: HH | ||
| M6 (amide-hydrolyzed apixaban) |
| Rat: RH |
| Mouse: MH | ||
| Rabbit: N.D. | ||
| Dog: N.D. | ||
| Monkey: N.D. | ||
| Human: N.D. | ||
| M7 (30-hydroxy apixaban) |
| Rat: plasma, urine, feces, bile, RH |
| Mouse: plasma, urine, feces, MH | ||
| Rabbit: feces | ||
| Dog: urine, feces, DH | ||
| Monkey: MKH | ||
| Human: plasma, urine, feces, bile, HH | ||
| M8 (hydroxy O-demethyl apixaban) |
| Rat: urine, bile |
| Mouse: N.D. | ||
| Rabbit: N.D. | ||
| Dog: urine, feces | ||
| Monkey: N.D. | ||
| Human: N.D. | ||
| M9 (hydroxy apixaban) |
| Rat: urine, feces, bile |
| Mouse: urine | ||
| Rabbit: N.D. | ||
| Dog: N.D. | ||
| Monkey: N.D. | ||
| Human: N.D. | ||
| M10 (hydroxy O-demethyl apixaban sulfate) |
| Rat: N.D. |
| Mouse: plasma | ||
| Rabbit: N.D. | ||
| Dog: N.D. | ||
| Monkey: N.D. | ||
| Human: plasma, feces | ||
| M13 (hydroxy O-demethyl apixaban) |
| Rat: N.D. |
| Mouse: plasma, urine | ||
| Rabbit: N.D. | ||
| Dog: N.D. | ||
| Monkey: N.D. | ||
| Human: feces | ||
| M14 (O-demethyl apixaban glucuronide) |
| Rat: N.D. |
| Mouse: plasma | ||
| Rabbit: plasma, urine | ||
| Dog: N.D. | ||
| Monkey: N.D. | ||
|
| Human: N.D. |
-
N.D., not detected; RH, rat hepatocytes; MH, mouse hepatocytes; DH, dog hepatocytes; MKH, monkey hepatocytes; HH, human hepatocytes.
-
↵ a M16 as an uncharacterized oxygenated metabolite was found in rabbit urine.
-
↵ b The structures of metabolites were identified based on LC-MS analyses and mass spectral comparison with those of parent and known metabolites.
-
↵ c Lactam ring-opened metabolites M3 and M5 were detected in hepatocyte incubations but not in vivo in mouse or human.