TABLE 2

AUC0–12 h of capmatinib and its metabolites in plasma

The AUC0–12 h of capmatinib and its major metabolites was determined in plasma.

PeakaCompound/MetaboliteAUC0–12 h
Mean ± S.D., N = 6b,c
(µmol·h/l)(% of total14C)
M28C-hydroxylationd and N-dealkylation5.40±3.145.9±1.6
M8 (CMN290)C-hydroxylation of methylene group5.06±2.515.4±1.6
M26Hydrogenation1.87±0.6582.2±0.5
M16 (CMN288)eImidazo-triazinone formation18.9±7.8921.5±2.1
M18 (CNJ294)N-dealkylation2.81±1.702.9±1.0
M13 (CMC583)Formation of carboxylic acid1.56±0.5552.2±1.6
CapmatinibParent drug38.3±16.442.9±2.9
Sum of minor identified metabolite (each less than 2%)f8.02±3.598.9±0.9
Sum of unknown trace metabolites1.31±0.5312.2±2.6
Lost during sample processing and HPLC4.80±2.195.9±1.9
Total14C (total of radiolabeled components)88.0±36.2100
  • , not meaningful.

  • a Listed according to appearance in chromatogram.

  • b Mean values of N = 6 volunteers.

  • c Mean values are means of individual values.

  • d Hydroxylation on a carbon atom or further isomerization to lactam moiety.

  • e Mean AUCinf was assessed and amounted to 20.3 ± 7.50 μmol·h/l (21.2% ± 2.2% of total 14C).

  • f Details available in Supplemental Table 1.