TABLE 4.
Plasma Pharmacokinetics
| Day | Cmax/D(ng/mL/mg) | tmax(h) | t1/2(h) | AUC0−12 / 0−12(ng/mL*h/mg) | Cl/F(L/h) | ||
|---|---|---|---|---|---|---|---|
| Agent | Stratum | Mean(Range) | Mean(Range) | Mean(Range) | Mean(Range) | Mean(Range) | |
| Imatinib | A(N=14) | 8 | 4.46(1.20−9.25) | 3.64(1.50−4.00) | 10.7(6.9−25.0) | 22.4(5.40−52.7) | 23.9(7.59−74.1) |
| 35 | 6.05(4.50−9.25) | 4.21(1.00−6.00) | 10.6(2.10−18.7) | 47.9(19.4−75.0) | 9.78(5.33−20.6) | ||
| P day 8 vs 35 | 0.011 | 0.461 | 0.840 | 0.0004 | 0.0004 | ||
| B(N=9) | 8 | 2.78(0.60−4.00) | 2.11(1.00−4.00) | 3.99(3.00−5.70) | 10.1(2.80−18.0) | 66.5(27.8−178.6) | |
| 35 | 4.20(1.60−8.40) | 2.56(0.00−4.00) | 4.58(1.20−8.80) | 39.4(10.4−62.1) | 16.4(8.05−48.1) | ||
| P day 8 vs 35 | 0.295 | 0.500 | 0.932 | 0.0003 | 0.0003 | ||
| P stratum A vs B | 8 | 0.040 | 0.006 | 0.0000006 | - | 0.0004 | |
| 35 | 0.008 | 0.029 | 0.001 | - | 0.034 | ||
| Vatalinib | A(N=15) | 7 | 3.12(0.72−5.03) | 1.86(0.97−3.00) | 3.80(1.35−8.54) | 11.1(2.23−16.1) | 122(62.0−448) |
| 35 | 2.82(0.82−7.38) | 2.45(1.00−4.42 | 2.62(1.44−5.13) | 10.4(3.28−25.5) | 137(39.3−305) | ||
| P day 7 vs 35 | 0.289 | 0.088 | 0.050 | 0.437 | 0.436 | ||
| B(N=8) | 7 | 1.15(0.40−2.46) | 1.79(1.00−3.17) | 5.13(1.47−14.4) | 4.51(1.31−12.1) | 377(82.3−765) | |
| 35 | 1.91(0.16−6.52) | 2.13(0.00−4.00) | 3.30(1.25−5.88) | 6.75(0.73−17.7) | 368(56.5−1371) | ||
| P day 7 vs 35 | 0.735 | 0.375 | 0.329 | 0.494 | 0.494 | ||
| P stratum A vs B | 7 | 0.001 | 0.779 | 0.550 | - | 0.001 | |
| 35 | 0.088 | 0.451 | 0.527 | - | 0.073 | ||
| CGP74588 | A(N=14) | 8 | 0.77(0.25−1.25) | 3.43(2.00−6.00) | 13.5(2.40−30.7) | 5.29(1.00−14.2) | - |
| 35 | 1.48(0.75−4.25) | 3.57(1.00−8.00) | 18.4(2.20−52.8) | 17.8(3.20−52.1) | - | ||
| P day 8 vs 35 | 0.0005 | 0.938 | 0.263 | 0.000007 | - | ||
| B(N=6) | 8 | 0.77(0.40−1.60) | 2.83(1.00−4.00) | 4.42(1.40−6.50) | 2.97(1.30−5.40) | - | |
| 35 | 1.50(0.80−2.80) | 3.25(1.50−6.00) | 5.25(1.50−11.7) | 24.7(8.40−54.4) | - | ||
| P day 8 vs 35 | 0.004 | 0.750 | 0.926 | 0.002 | |||
| P stratum A vs B | 8 | 0.866 | 0.392 | 0.002 | - | - | |
| 35 | 0.824 | 0.845 | 0.005 | - | - | ||
| - | - | - | - | - | |||
| Hydroxyurea | A(N=14) | 8 | 18.5(6.80−29.6) | 1.29(0.50−2.00) | 4.84(1.60−12.5) | 50.4(9.50−91.1) | 15.2(5.50−52.5) |
| 35 | 19.4(5.60−32.6) | 1.30(0.50−4.00) | 3.29(1.40−6.80) | 41.7(13.0−84.5) | 15.4(5.90−38.4) | ||
| P day 8 vs 35 | 0.931 | 0.441 | 0.020 | 0.246 | 0.248 | ||
| B(N=6) | 8 | 16.5(7.60−35.0) | 1.80(0.50−4.00) | 3.5(2.70−5.40) | 37.38(18.1−60.4) | 16.4(8.3−27.6) | |
| 35 | 19.0(7.80−31.4) | 0.90(0.50−1.50) | 7.12(2.50−21.5) | 41.4(17.0−70.1) | 15.4(7.10−29.4) | ||
| P day 8 vs 35 | 0.615 | 0.415 | 0.723 | 0.718 | |||
| P stratum A vs B | 8 | 0.467 | 0.554 | 0.373 | 0.517 | 0.516 | |
| 35 | 0.848 | 0.852 | 0.123 | 0.964 | 0.965 |