TABLE 1

Pharmacokinetic parameter estimates of PF02341066 in athymic mice bearing GTL16 or U87MG tumors after repeated oral administration of PF02341066 Precision of the estimates is expressed as S.E. in parentheses.


Study

Dose

ka

CL/F

V/F
mg/kg h–1 liters/h/kg liters/kg
PKPD 1 8.5 0.291 (0.014) 9.23 (1.46) 32.0 (5.9)
17 0.282 (0.014) 4.70 (0.95) 16.6 (4.1)
34 0.300 (0.026) 1.53 (0.40) 3.23 (3.13)
PKPD 2 6.25 0.238 (0.012) 13.6 (1.9) 56.0 (9.9)
12.5 0.336 (0.013) 2.71 (0.57) 8.02 (2.30)
25 0.326 (0.014) 2.38 (0.35) 7.25 (1.29)
50 0.331 (0.018) 1.80 (0.17) 5.56 (0.68)
PKPD 3 6.25 0.248 (0.016) 7.83 (1.10) 31.6 (4.8)
12.5 0.240 (0.018) 3.11 (0.24) 5.04 (1.22)
25 0.238 (0.015) 2.83 (0.16) 3.32 (0.75)

50
0.242 (0.010)
1.98 (0.18)
2.49 (0.52)
  • PKPD 1 and 2, athymic mice bearing GTL16 human gastric carcinoma; PKPD 3, athymic mice bearing U87MG human glioblastoma; ka, absorption rate constant; CL/F, oral clearance; V/F, oral volume of distribution