The decrease in systemic imatinib exposure during the first months of treatment is not likely to be caused by increased clearance due to fluctuations in alpha-1 acid glycoprotein levels. |
Since systemic imatinib exposure varies over time, pharmacokinetic sampling should be performed at standardized time points. |
1 Background
2 Methods
2.1 Patients
2.2 Study Procedures
2.3 Statistical Considerations
3 Results
3.1 Baseline
Characteristic | Patients, n = 28 |
---|---|
Age at start | |
Years | 69 (10) |
Sex | |
Male | 16 (57 %) |
Female | 12 (43 %) |
WHO performance status | |
0 | 12 (43 %) |
1 | 13 (46 %) |
2 | 1 (4 %) |
Unknown | 2 (7 %) |
c-KIT mutation | |
Wild type | 5 (18 %) |
Exon 9 | 6 (21 %) |
Exon 11 | 12 (43 %) |
Exon 13 | 3 (11 %) |
Unknown | 2 (7 %) |
Treatment setting | |
Neoadjuvant | 11 (39 %) |
Adjuvant | 5 (18 %) |
Palliative | 12 (43 %) |
Dose at start | |
300 mg QD | 1 (4 %) |
400 mg QD | 26 (93 %) |
800 mg QD | 1 (4 %) |
3.2 AGP Levels and Imatinib Concentrations
Time point 1, n = 25 | Time point 2, n = 25 | Time point 3, n = 19 | Total, n = 69 | |
---|---|---|---|---|
Actual time since start of imatinib [days]a
| 30 (3) | 97 (30) | 364 (20) | |
AGP level [g/L]b
| 0.97 (0.85–1.10) | 0.81 (0.69–0.94) | 0.89 (0.78–1.00) | 0.89 (0.82–0.96) |
Imatinib concentration [ng/mL]b
| 1457 (1155–1838) | 1305 (1001–1702) | 1193 (967–1472) | 1325 (1158–1516) |
CGP74588 concentration [ng/mL]b
| 308 (247–384) | 265 (205–343) | 231 (179–299) | 270 (235–309) |
Imatinib + CGP74588 concentration [ng/mL]b
| 1777 (1420–2224) | 1578 (1217–2047) | 1439 (1165–1777) | 1606 (1407–1833) |
Correlation between imatinib and AGPc
| 0.526 (P < 0.001) | 0.839 (P < 0.001) | 0.411 (P = 0.003) | 0.656 (P < 0.001) |