Table 3.

Pharmacokinetic parameters of motesanib when administered with or without carboplatin/paclitaxel

ParameterArm A
Cycle 1 (day 3, −CP)Cycle 2 (day 1, +CP)Cycle 2 to Cycle 1
Mean ± SDMean ± SDGLSM ratio (90% CI)
50 mg once daily(n = 3-4)(n = 2-4)
    tmax,* h0.75 (0.50-2.0)1.5 (1.0-2.0)
    Cmax, ng/mL158 ± 55148 ± 250.97 (0.57-1.66)
    t1/2,z, h7.34 ± 2.074.98 ± NR
    AUC, μg·h/mL0.971 ± 0.3001.05 ± NRNE
    C24 h, ng/mL9.12 ± 4.175.61 ± NR
125 mg once daily(n = 7-9)(n = 5-9)
    tmax,* h1.0 (0.5-6.0)1.0 (0.5-4.0)
    Cmax, ng/mL525 ± 250748 ± 7010.98 (0.48-2.01)
    t1/2,z, h5.33 ± 1.056.41 ± 2.08
    AUC, μg·h/mL3.21 ± 1.124.50 ± 2.621.42 (0.89-2.26)
    C24 h, ng/mL26.5 ± 16.843.4 ± 44.8
75 mg twice daily(n = 5-6)(n = 5-6)
    tmax(0-12 h),* h0.75 (0.25-1.0)0.63 (0.25-4.0)
    Cmax(0-12 h), ng/mL448 ± 112390 ± 319
    t1/2,z(0-12 h), h5.77 ± 1.456.36 ± 1.70
    AUC0-24 h, μg·h/mL2.91 ± 1.013.11 ± 2.38
    C24 h, ng/mL56.7 ± 27.445.4 ± 35.9

Abbreviations: AUC0-24 h, AUC from time 0-24 h; C24 h, plasma concentration at 24 h; NE, not estimated because only one subject had AUC data for cycles 1 and 2; NR, not reported; t1/2,z, estimated terminal phase half-life; tmax, time at which maximum plasma concentration was observed.

  • *tmax and tmax(0-12 h) are reported as a median (range) value.

  • For once daily cohorts, AUC0-∞ is reported for cycle 1 and AUC0-24 is reported for cycle 2.

  • SD not reported if n < 3.