TABLE 2

Pharmacokinetics (mean ± S.E.M. where appropriate) of naveglitazar (S-enantiomer), LY591026 (R-enantiomer), and radioactivity in mice, rats, and monkeys after administration of [14C]naveglitazar

Mouse 10 mg/kg Oral
Rat (n = 3) 10 mg/kg Oral
Monkey (n = 4) 5 mg/kg Oral
Monkey (n = 4) 1 mg/kg i.v.
Naveglitazar
    Cmax (μg/ml) 16.4 49.3 ± 2.43 44.0 ± 3.3 23.9 ± 525a
    AUC0-last (μg · h/ml) 97.0 254 ± 7.75 499 ± 35.2 94.0 ± 9.43
    AUC0-∞ (μg · h/ml) 97.3 254 515 ± 45 94.0 ± 9.43
    Tmax (h) 2.0 1.0 2.8 ± 0.8 0a
    Half-life (h) 53.8 14.3 199 ± 75.3 32.3 ± 4.3
    CL/F (ml/min/kg) 1.71 0.66 0.16 ± 0.02 0.18 ± 0.02b
    Vss/F (l/kg) 0.58 0.17 0.16 ± 0.1 0.11 ± 0.0b
LY591026
    Cmax (μg/ml) 0.550 1.60 ± 0.02 2.2 ± 0.2 0.635 ± 0.019
    AUC0-last (μg · h/ml) 6.48 15.1 ± 0.33 38.4 ± 2.6 7.14 ± 1.35
    AUC0-∞ (μg · h/ml) 6.48 15.1 38.4 ± 2.6 7.14 ± 1.35
    Tmax (h) 4.0 2.0 3.5 ± 0.5 1.5 ± 0.3
    Half-life (h) 6.31 13.9 29.4 ± 6.8 22.0 ± 3.4
Radioactivity
    Cmax (μg-Eq/ml) 21.2 59.2 ± 1.75 56.6 ± 2.5 21.8 ± 0.797a
    AUC0-last (μg-Eq · h/ml) 182 367 ± 9.75 1300 ± 150 224 ± 7.76
    AUC0-∞ (μg-Eq · h/ml) 186 371 1300 ± 151 225 ± 7.76
    Tmax (h) 2.0 1.0 2.8 ± 0.8 0a
    Half-life (h) 48.1 21.4 158 ± 16.9 166 ± 13.0
    CL/F (ml/min/kg) 0.90 0.45 0.07 ± 0.01 0.07 ± 0b
    Vss/F (l/kg) 0.80 0.21 0.20 ± 0.01 0.26 ± 0.03b
    Percentage of naveglitazar total radioactivity
53
69
38
42

  • μg-Eq = microgram equivalents of naveglitazar-related material.

  • ↵ a Extrapolated values.

  • ↵ b Represents true clearance and/or volume of distribution at steady state.