Effect of CLI on the PK parameters of imatinib and on its binding to plasma proteins
| Patient . | Day 4a . | . | . | . | . | . | Day 5f . | . | . | . | . | . | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | Cmaxb (μg/ml) . | AUCc (μg/ml h) . | Clssd (liter/h) . | Vssd (liter) . | % bound . | Free imatinibe (μg/ml) . | Cmax (μg/ml) . | AUC (μg/ml h) . | Clss (liter/h) . | Vss (liter) . | % bound . | Free imatinib (μg/ml) . | ||||||||||
| 001 | 8.09 | 70.47 | 5.68 | 84.7 | 99.5 | 0.04 | 1.79 | 30.20 | 13.25 | 172.6 | 98.5 | 0.052 | ||||||||||
| 002 | 2.90 | 42.70 | 9.37 | 185.2 | 97.4 | 0.0654 | 1.04 | 14.30 | 27.97 | 585.3 | 93.8 | 0.0645 | ||||||||||
| 0503 | 3.06 | 43.20 | 9.26 | 152.3 | 99.2 | 0.0245 | 0.73 | 16.59 | 24.11 | 434.9 | 94.6 | 0.0394 | ||||||||||
| 0502 | 7.08 | 97.70 | 4.09 | 86.3 | 99.5 | 0.0354 | 1.57 | 20.00 | 20.00 | 519.5 | 95.5 | 0.0707 | ||||||||||
| 0501 | 2.49 | 33.38 | 11.98 | 266.8 | 99.5 | 0.0125 | 1.02 | 16.40 | 24.39 | 876.4 | 97.6 | 0.0245 | ||||||||||
| Mean | 4.72 | 57.49 | 8.08 | 155.1 | 99.02 | 0.035 | 1.43 | 19.50 | 21.94 | 517.7 | 96.0 | 0.051 | ||||||||||
| 95% CI | 3.30 | 23.15 | 2.77 | 66.6 | 1.07 | 0.02 | 1.02 | 5.54 | 4.93 | 223.1 | 2.41 | 0.019 | ||||||||||
| Patient . | Day 4a . | . | . | . | . | . | Day 5f . | . | . | . | . | . | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | Cmaxb (μg/ml) . | AUCc (μg/ml h) . | Clssd (liter/h) . | Vssd (liter) . | % bound . | Free imatinibe (μg/ml) . | Cmax (μg/ml) . | AUC (μg/ml h) . | Clss (liter/h) . | Vss (liter) . | % bound . | Free imatinib (μg/ml) . | ||||||||||
| 001 | 8.09 | 70.47 | 5.68 | 84.7 | 99.5 | 0.04 | 1.79 | 30.20 | 13.25 | 172.6 | 98.5 | 0.052 | ||||||||||
| 002 | 2.90 | 42.70 | 9.37 | 185.2 | 97.4 | 0.0654 | 1.04 | 14.30 | 27.97 | 585.3 | 93.8 | 0.0645 | ||||||||||
| 0503 | 3.06 | 43.20 | 9.26 | 152.3 | 99.2 | 0.0245 | 0.73 | 16.59 | 24.11 | 434.9 | 94.6 | 0.0394 | ||||||||||
| 0502 | 7.08 | 97.70 | 4.09 | 86.3 | 99.5 | 0.0354 | 1.57 | 20.00 | 20.00 | 519.5 | 95.5 | 0.0707 | ||||||||||
| 0501 | 2.49 | 33.38 | 11.98 | 266.8 | 99.5 | 0.0125 | 1.02 | 16.40 | 24.39 | 876.4 | 97.6 | 0.0245 | ||||||||||
| Mean | 4.72 | 57.49 | 8.08 | 155.1 | 99.02 | 0.035 | 1.43 | 19.50 | 21.94 | 517.7 | 96.0 | 0.051 | ||||||||||
| 95% CI | 3.30 | 23.15 | 2.77 | 66.6 | 1.07 | 0.02 | 1.02 | 5.54 | 4.93 | 223.1 | 2.41 | 0.019 | ||||||||||
Day 4 refers to PK performed at SS.
Cmax values were obtained from experimental data.
AUCs were calculated by trapezoidal rule.
Clearance (Clss) and the volume of distribution (Vss) were calculated as described in “Patients and Methods.”
The percentage of free imatinib and free imatinib concentrations were experimentally measured by ultrafiltration and HPLC determination.
Day 5 refers to PK performed during CLI infusion, 24 h after the day 4 PK.