Pharmacokinetic parameters for 14C radioactivity in blood and plasma and of imatinib and CGP74588 in plasma Pharmacokinetic parameters of 14C radioactivity in blood and plasma and of imatinib and its N-desmethyl metabolite CGP74588 in plasma of healthy male subjects after a single oral dose of 239 mg of 14C-labeled imatinib mesylate are shown. Mean ± S.D., n = 4.
Radioactivity | Imatinib | CGP74588 | |||
|---|---|---|---|---|---|
| Blood | Plasma | Plasma | |||
| Cmax (μmol/l) | 1.57 ± 0.07 | 2.02 ± 0.09 | 1.87 ± 0.19 | 0.24 ± 0.05 | |
| Cmax (μg/ml) | 0.775 ± 0.03a | 0.999 ± 0.043a | 0.921 ± 0.095 | 0.115 ± 0.026 | |
| Cmax (% 14C in plasma) | 78 ± 5 | 100 | 92 ± 6 | 12 ± 2 | |
| tmax (h) | Range: 1 to 2 | Range: 1 to 2 | Range: 1 to 2 | Range: 1 to 1.5 | |
| Median: 1.75 | Median: 1.5 | Median: 1.25 | Median: 1.25 | ||
| AUC0–24 h (μmol·h/l) | 18.5 ± 0.6 | 24.9 ± 0.9 | 16.2 ± 1.2 | 2.13 ± 0.33 | |
| AUC0–24 h (μg·h/ml) | 9.1 ± 0.3a | 12.3 ± 0.4a | 8.01 ± 0.57 | 1.02 ± 0.16 | |
| AUC0–24 h (% 14C in plasma) | 74 ± 3 | 100 | 65 ± 3 | 9 ± 1 | |
| AUC0–48 h (μmol·h/l) | 25.7 ± 0.99 | 34.6 ± 1.7 | 20.0 ± 1.8 | 2.85 ± 0.37 | |
| AUC0–48 h (μg·h/ml) | 12.7 ± 0.49a,b | 17.1 ± 0.82a | 9.89 ± 0.90 | 1.37 ± 0.18 | |
| AUC0–48 h (% 14C in plasma) | 75 ± 2 | 100 | 58 ± 3 | 8.0 ± 1.0 | |
| AUC0–168 h (μmol·h/l) | n.a. | 48.5 ± 2.6 | n.a. | n.a. | |
| AUC0–168 h (μg·h/ml) | n.a. | 23.9 ± 1.3a | n.a. | n.a. | |
| AUC0-∞ (μmol·h/l) | 31.9 ± 1.5 | 53.1 ± 2.0 | 21.6 ± 2.3 | 3.47 ± 0.39 | |
| AUC0-∞ (μg·h/ml) | 15.8 ± 0.76a | 26.2 ± 1.0a | 10.7 ± 1.1 | 1.66 ± 0.19 | |
| AUC extrapolated (%) | 25.3 ± 14 | 8.7 ± 2.0 | 7.3 ± 1.3 | 17.9 ± 2.2 | |
| AUC0-∞ (% 14C in plasma) | 60 ± 0.9 | 100 | 41 ± 4 | 6.5 ± 0.8 | |
| t1/2λz (h) terminal | 21.2 ± 1.13 | 57.3 ± 12.5 | 13.5 ± 0.9 | 20.6 ± 1.7 | |
| Time period | 12 to 48 hc | 72 to 168 hd | 12 to 48 h | 12 to 48 h | |
| Hematocrit (%) | 43 ± 1 | – | – | – | |
| Binding to RBC (%) | 23 ± 5e | – | – | – | |
| CL/f [(ml/min)/kg]f | – | – | 4.18 ± 0.29 | – | |
| CL/f (l/h) | – | – | 18.9 ± 2.0 | – | |
| Vz/f (l/kg)f | – | – | 4.90 ± 0.55 | – | |
| Vz/f (liter) | – | – | 366 ± 19 | – | |
–, Not calculated or not meaningful; n.a., not available; RBC, red blood cells.
↵ a Radioactivity concentrations are expressed as microgram equivalents of imatinib free base per ml (= μg eq/ml)
↵ b Mean ± S.D., n = 3 of subjects
↵ c Two of four subjects. For the other two subjects, the periods of 48 to 72 and 8 to 24 h were considered
↵ d Two of four subjects. For the other two subjects, the periods of 48 to 168 h or 1.5 to 168 h were considered
↵ e Calculated from the blood and plasma 14C concentrations at time points in the period of 0 to 48 h
↵ f Factor f means the systemic bioavailability of the drug