TABLE 3

Average pharmacokinetic parameters of vatalanib and 14C radioactivity after a single dose of 1000 mg of 14C-radiolabeled vatalanib administered at steady state, obtained after 14 consecutive daily oral doses of 1000 mg of nonradiolabeled vatalanib

Mean ± S.D., n = 7 patients.

Pharmacokinetic Parameter
Unita
Total 14C Radioactivity in Plasma after Single Dose
Vatalanib in Plasma at Steady State
t max h 3.5 ± 2.7 1.8 ± 1.1
2 (median) 1.5 (median)
C max μmol/l 38.3 ± 26.0 15.8 ± 9.5
μg/mlb 13.3 ± 9.0 5.47 ± 3.29
C min μmol/l 1.08 ± 1.49
μg/mlb 0.375 ± 0.517
AUC0-24h μmol · h/l 487 ± 382
μg · h/mlb 169 ± 133
AUC0-∞ or AUCssτ μmol · h/l 907 ± 792 73.7 ± 59.0
μg · h/mlb 314 ± 275 25.6 ± 20.5
Vatalanib AUCssτ/14C AUC ratio % 9.0 ± 4.3
Vz/f liters 337 ± 234
CLss/f l/h 56.1 ± 47.3
Estimated oral absorption % of dose 35 (range, 18-57)
Blood/plasma 14C radioactivity concentration ratioc 0.70 ± 0.04
14C radioactivity confined to red blood cellsc % 22 ± 7
Apparent terminal elimination half-life (t1/2λz) h 23.4 ± 5.5 4.6 ± 1.1
Time interval for t1/2λz calculation
h
12-72 h
6 or 8 to 24 h

  • ↵ a To convert micromolar units into microgram units, multiply by 0.3468 (vatalanib free base).

  • ↵ b μg-Eq/ml and μg-Eq · h/ml for concentration and AUC of total 14C radioactivity.

  • ↵ c Calculated at about Cmax up to 12 h, assuming a hematocrit of 0.45, mean ± S.D. of n = 5 patients.