Table 7

Geometric mean (%CV) pharmacokinetic parameter values for BMS-184476 and its metabolites after administration of a 60-min i.v. infusion of BMS-184476

7 mg/m228 mg/m240 mg/m250 mg/m260 mg/m2
Cmax, nM
 BMS-184476200710 (2.1)1076 (19.9)1563 (18.0)1854 (49.1)
 BMS-246178NDa16.4 (31.5)27.6 (52.3)32.7 (33.4)59.6 (27.9)
 BMS-246180ND13.4 (24.4)18.3 (43.5)23.9 (49.8)34.4 (58.5)
 PaclitaxelNDND18.9 (41.6)18.3 (25.1)17.4 (31.4)
Tmax, h (range)
 BMS-18447611 (0.5, 1)1 (0.5, 1)1 (0.5, 1)0.75 (0.5, 1)
 BMS-246178ND1.38 (1, 1.5)1 (1, 1.25)1 (1, 1.25)1.25 (1.25, 1.25)
 BMS-246180ND1 (1, 1.25)1 (1, 1.25)1 (1, 1.25)1.25 (1.25, 1.25)
 PaclitaxelNDND1.5 (1.25, 2)1.25 (1.25, 1.5)1.5 (1.5, 1.5)
AUC (24 h)b, nM·h
 BMS-1844766251722 (10.7)2063 (19.6)2760 (10.9)3712 (31.2)
 BMS-246178ND17.2 (43.1)26.7 (83.2)34.2 (27.7)96.7 (38.5)
 BMS-246180ND13.3 (47.2)19.1 (60.6)23.6 (18.5)47.6 (79.6)
 PaclitaxelNDND16.9 (55.7)17.1 (44.4)35.2 (95.0)
AUC (INF), nM·h
 BMS-184476NDNDND4634 (14.9)6306 (5.9)
T-HALF, h
 BMS-184476NDNDND34.4 (16.4)33.5 (14.5)
CLT, mL/min/m2
 BMS-184476NDNDND199 (27.8)172 (12.1)
VSS, liter/m2
 BMS-184476NDNDND379 (161)350 (223)
%UR
 BMS-184476ND0.62 (0.21)0.78 (0.24)0.61 (0.20)0.39 (0.01)
 BMS-246178ND0.08 (0.03)0.08 (0.03)0.06 (0.02)0.09 (0.01)
 BMS-246180ND0.06 (0.01)0.12 (0.21)0.05 (0.02)0.06 (0.02)
 PaclitaxelNDND0.20 (0.09)0.14 (0.05)0.12 (0.01)
  • a ND, not determined as sample collection was incomplete or all of the concentrations were < LLQ.

  • b AUC(T) for metabolites where T represents the last detectable timepoint.