TABLE 6

Quantitative estimate of radioactivity of metabolites in excreta in healthy male volunteers after a single 20-mg oral dose of [14C]-osimertinib and semiquantification by ultraviolet (UV) light spectroscopy of circulating metabolites in area under the curve (AUC)(0-24 h) human plasma pool extract in patients with non-small cell lung cancer after oral administration of multiple doses of osimertinib (80 mg/day, day 22)

ComponentDescriptionModificationPercentage of Administered Dose in Healthy VolunteersPercentage Relative to Total Drug-Related UV Response in Patientsb
Feces (Pooled 24–168 h)Urine (Pooled 0–168 h)Plasma Pool
ParentOsimertinibNA1.20.7176
M1Oxidation+OND0.13<2c
M2Dealkylation–C4H9NNDND4
AZ7550Demethylation- CH22.30.446c
AZ5104Demethylation- CH25.60.968c
M8Cysteine-glycine adduct+C5H10O3N2SNDND2
M17Oxidation+O0.33ND<2
M18Oxidation and glucuronidation+C6H8O7NDND<2
M19UnknownUnknown0.80NDND
M20Oxidation+O0.76NDND
M21Cysteinyl adduct+C3 H6 O2 NS1.5NDND
M22UnknownUnknown0.48NDND
M23Dealkylation + oxidation-C4 H9 N, +O0.47NDND
M24UnknownUnknownNDa0.25ND
M25UnknownUnknownND1.9ND
Total144.4NA
  • NA, not applicable, ND, not detected.

  • a Peak in accelerator mass spectrometry (AMS) profile had similar retention to M20 in feces AMS profile but no mass ion to confirm identity.

  • b Lower limit of quantitation = 2% of osimertinib UV (310–350 nm) response.

  • c Metabolites confirmed with authentic standard.