TABLE 3

Percentage of radioactivity of casopitant and its relevant metabolites in mouse, rat, and dog plasma after a single-dose oral administration of [14C]casopitant

M44, M117 (male rat), M114, M115 (rat and dog), and M136 (dog) were nonradiolabeled metabolites observed by mass spectrometry only. Observed metabolite radioactivity was determined by 96-well fraction collection with scintillation counting for 5 min after a chromatographic separation was performed by HPLC. Percentages obtained from the radiochromatogram were adjusted for the extraction recovery. The percentage of radioactivity per time point does not equal 100% because only distinct radioactive peaks were assigned values and only those greater than 5% of plasma radioactivity in at a least one species were reported in the table.

PeakPlasma Radioactivitya
Mice (50 mg/kg), MaleRat (15 mg/kg)Dog (10 mg/kg), Male
MaleFemale
0.5 h6 h2 h8 h2 h8 h1 h6 h
%
Casopitant12.26.513.23.945.443.125.612.0
M35.86.039.420.52.7 (+M166)4.9 (+M166)BQLN.D.
M9N.D.N.D.N.D.N.D.1.7 (+M112)1.2 (+M112)5.64.2
M104.4 (+M69)4.0 (+M69)1.41.21.61.35.34.0
M12 + M69N.D.N.D.3.23.74.57.23.2 (+M154)3.1 (+M154)
M135.83.96.12.813.424.57.26.4
M1613.53.9N.D.N.D.N.D.N.D.N.D.N.D.
M177.01.1N.D.N.D.N.D.N.D.N.D.N.D.
M2818.05.6N.D.N.D.N.D.N.D.3.53.2
M31 + M134N.D.N.D.4.36.18.97.311.716.8
M57 + M155N.D.N.D.N.D.N.D.N.D.N.D.3.45.7
M109N.D.N.D.N.D.N.D.10.10.84.3 (+M1)BQL (+M1)
Total μg Eq/g in plasma5.375.601.390.7621.762.106.284.91
  • BQL, below quantification limit, set to 25 cpm as peak area; N.D., not detected.