Table 4.

Mean (SD) mapatumumab pharmacokinetics

Dose (mg/kg)No. patientsCmax (μg/mL)AUC0-∞ (μg h/mL)t1/2,α (d)t1/2,β (d)CL (mL/d/kg)V1 (mL/kg)Vss (mL/kg)
0.0130.27 (0.03)5.11 (3.12)0.7 (0.4)28.4 (23.4)2.50 (1.42)37.32 (3.88)70.49 (20.81)
0.0330.84 (0.06)8.42 (1.58)0.7 (0.1)14.2 (4.3)3.65 (0.71)35.49 (2.58)69.05 (14.51)
0.357.45 (0.62)100.63 (34.01)0.8 (0.3)19.5 (9.8)3.32 (1.29)40.23 (3.31)77.88 (22.89)
3453.42 (13.86)780.31 (276.13)1.1 (1.1)21.2 (9.5)4.27 (1.66)57.46 (13.44)109.77 (16.13)
108159.83 (30.98)1981.72 (715.56)1.4 (0.8)16.4 (6.3)5.63 (1.91)63.85 (12.94)110.64 (25.98)
2012405.10 (96.67)5635.42 (2094.73)1.4 (0.9)27.3 (27.5)4.24 (2.34)51.08 (11.55)116.83 (55.69)
P*0.00020.06050.14110.71710.06050.00030.0370
  • Abbreviations: Cmax, maximum plasma mapatumumab concentration; AUC0-∞, area under the plasma mapatumumab concentration-time curve to infinite time; t1/2,α, initial phase elimination half-life; t1/2,β, terminal phase elimination half-life; CL, clearance; V1, volume of distribution for the central compartment; Vss, volume of distribution at steady state.

  • * From a one-way ANOVA of log-transformed values. Cmax and AUC0-∞ were dose normalized before analysis.

  • Significant difference between the 10 mg/kg group and the 0.01, 0.03, and 0.3 mg/kg groups; P < 0.001, Bonferroni's multiple comparison test.

  • No significant differences in any pairwise comparison; P > 0.05, Bonferroni's multiple comparison test.