Table 5. Summary of pharmacokinetic values (arithmetic mean (coefficient of variation)) for sunitinib, SU012662, sunitinib+SU012662, irinotecan, and its active metabolite SN-38 for all doses combined (paired observations only).
| Pharmacokinetic parameter | Sunitinib alone C0D–7, mean (CV%) | Irinotecan alone C1D1, mean (CV%) | Sunitinib+irinotecan C2D1, mean (CV%) | Geometric mean ratio (C2D1/C0D–7 or C2D1/C1D1) |
|---|---|---|---|---|
| Sunitinib (n=18)a | ||||
| Tmax (h)b | 8 (4–24) | NA | 8 (2–29) | |
| Tlast (h)c | 24.0 | NA | 24.0 | |
| Cmax (ng l−1) | 16.3 (39.2) | NA | 13.0 (31.8) | 0.82 |
| AUC0–last (ng h ml−1) | 266.5 (41.2) | NA | 225.5 (29.5) | 0.88 |
| SU012662 (n=18)a | ||||
| Tmax (h)b | 7 (2–24) | NA | 24 (1.8–29) | |
| Tlast (h)c | 24.0 | NA | 24.0 | |
| Cmax (ng ml−1) | 2.4 (51.4) | NA | 3.6 (32.5) | 1.6 |
| AUC0–last (ng h ml−1) | 38.6 (54.4) | NA | 53.2 (30.9) | 1.48 |
| Total drug (n=18)a | ||||
| Tmax (h)b | 8 (4–24) | NA | 9 (2–29) | |
| Tlast (h)c | 24.0 | NA | 24.0 | |
| Cmax (ng ml−1) | 18.5 (40.3) | NA | 16.2 (29.7) | 0.90 |
| AUC0–last (ng h ml−1) | 305.2 (42.1) | NA | 278.2 (28.7) | 0.95 |
| Irinotecan (n=18–20)c | ||||
| Tmax (h)b | NA | 1 (1–1.7) | 1 (0.9–1.7) | |
| Tlast (h)c | NA | 24.0 | 24.0 | |
| Cmax (μg ml−1) | NA | 2.9 (21.3) | 3.6 (26.8) | 1.21 |
| AUC0–last (μg h ml−1) | NA | 14.9 (27.7) | 16.9 (33.3) | 1.12 |
| AUC0–∞ (μg h ml−1) | NA | 15.9 (29.3) | 18.1 (34.0) | 1.13 |
| CL (l h−1) | NA | 31.9 (30.3) | 30.4 (28.8) | |
| t1/2 (h) | NA | 6.3 (19.8) | 6.6 (21.9) | |
| SN-38 (n=18–20)c | ||||
| Tmax (h)b | NA | 1.1 (1.0–4.2) | 1.5 (0.9–4.1) | |
| Tlast (h)c | NA | 24.0 | 24.0 | |
| Cmax (μg ml−1) | NA | 0.03 (51.4) | 0.04 (50.0) | 1.13 |
| AUC0–last (μg h ml−1) | NA | 0.31 (61.7) | 0.36 (52.8) | 1.20 |
Abbreviations: AUC0–∞=area under the plasma concentration–time curve (AUC) from time zero to infinity; AUC0–last=AUC from time zero to the last quantifiable sampling time point; C0D–7=cycle 0 (screening) day –7; C1D1=cycle 1 day 1; C2D1=cycle 2 day 1; CL=clearance; Cmax=maximum plasma concentration; CV=coefficient of variation; NA=not applicable; t1/2=terminal elimination half-life; Tlast=time when last sample collected; Tmax=time to Cmax.
a
Pharmacokinetic parameters estimated on C2D1 were corrected for carryover pre-dose concentrations where applicable.
b
Median and range values presented for the parameter Tmax.
c
Median value reported for Tlast.