TABLE 4

Output values for atomoxetine, 4-hydroxyatomoxetine, and N-desmethylatomoxetine by humanized liver mouse PBPK modeling

Numbers in parentheses indicate fold values relative to the experimental results shown in Figs. 3 and 4.

ParameterAtomoxetine4-HydroxyatomoxetineN-Desmethylatomoxetine
Untreated
 Plasma
  Cmax, ng/ml (fold to experimental)758 (2.9)1250 (0.52)2.39 (1.1)
  AUC, ng h/ml (fold)1250 (2.5)8760 (1.2)31.6 (1.9)
 Urine, 0–24 h
  Mean concentration (fold, range), μg/ml1.16 (6.7, 4.4–15)132 (2.7, 2.2–4.2)0.028 (14, 8.9–34)
Treated with paroxetine
 Plasma
  Cmax, ng/ml783 (1.4)750 (1.4)12.7 (0.43)
  AUC, ng h/ml2090 (0.58)6440 (0.80)186 (0.35)
 Urine, 0–24 h
  Mean concentration (fold, range), μg/ml1.93 (2.0, 1.5–3.0)97.2 (3.5, 2.8–6.4)0.166 (1.1, 0.60–2.6)