TABLE 5

Mean percentage of administered dose of casopitant and its relevant metabolites in excreta after a single oral dose of [14C]casopitant to mice, rats, and dogs

M44, M114, M115, and M136 were nonradiolabeled metabolites observed in all tree species by mass spectrometry only. Percentages were obtained from the radiochromatogram have been adjusted for the sample treatment recovery. The total percentage of the dose excreted in each matrix does not equal to the sum of metabolite percentages, because not all the time points were pooled and a few minor metabolites were not reported.

Peak%Administered Dosea
Mice (50 mg/kg), MaleRat (15 mg/kg)Dog (10 mg/kg), Male
MaleFemale
Feces (intact)
    Casopitant1.51.14.00.3
    M1N.D.2.1 (+M41 + M42)6.8 (+M41)2.5 (+M181)
    M31.1 (+M9 + M205)0.92.73.2
    M13N.D.BQL3.70.5
    M28 + M1414.30.70.3N.D.
    M31 + M1340.6 (+M169)1.3 (+M169)9.0 (+M169)3.3
    M33N.D.1.0 (+M164)2.52.9
    M5022.251.32.3N.D.
    M616.2 (+M137)0.81.2 (+M63)N.D.
    M637.8 (+M16)3.61.2 (+M61)N.D.
    M76N.D.BQL4.6 (+M111 + M170)N.D.
    M807.110.4 (+M106)1.1N.D.
    M123N.D.1.2 (+M62 + M70)3.5 (+M62 + M70)4.6
    Total % dose in feces84.996.497.682.5
Bile
    CasopitantN.S.BQL0.50.4
    M1 + M42N.S.0.7 (+M41)1.50.8
    M3N.S.0.4N.D.1.7 (+M9 + M36)
    M12N.S.BQL0.5 (+M131)1.2
    M31 + M134N.S.BQL0.91.6 (+M13 + M57)
    M33N.S.0.71.71.5
    M37N.S.N.D.N.D.3.8 (+M81 + M82)
    M50N.S.9.0 (+M81)0.7N.D.
    M63N.S.1.5 (+M78)1.3N.D.
    M70N.S.0.8 (+M62 + M123)1.02.2 (+M123)
    M78N.S.1.5 (+M63)1.5N.D.
    M80N.S.3.7 (+M122 + M174)0.9 (+M81 + M82)N.D.
    M100 + M172N.S.6.9N.D.N.D.
    M103N.S.9.6 (+M102 + M106)3.4 (+M104)3.3
    M104N.S.0.9 (+M79 + M120)3.4 (+M103)1.9 (+M187)
    M118 + M171N.S.2.9N.D.N.D.
    M119N.S.5.2 (+M173)1.02.1
    M120N.S.0.9 (+M79 + M104)1.7 (+M122)N.D.
    M122N.S.3.7 (+M80 + M174)1.7 (+M120)N.D.
    M123N.S.0.8 (+M62 + M70)0.32.2 (+M70)
    M174N.S.3.7 (+M80 + M122)0.3N.D.
    M185N.S.N.D.N.D.1.3
    Total % dose in bileN.S.56.538.145.0
Urine (intact)
    CasopitantaBQLBQL
    M200.20.40.2N.D.
    M210.10.1BQL0.5 (+M198)
    M281.30.4 (+M22)0.21.3
    M161.70.3N.D.0.4
    M1380.10.10.20.9
    Total % dose in urine5.43.41.55.9
  • N.D., not detected; BQL, below quantification limit, set to 25 cpm as peak area; N.S., no sample.

  • a ✓, observed by HPLC-mass spectrometry only.