Table 3.
Summary of pharmacokinetic data carboplatin-derived unbound platinum in plasma and tissue
| Parameter | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 |
|---|---|---|---|---|---|---|
| Dose carboplatin (mg) | 700 | 1,150 | 850 | 780 | 700 | 780 |
| Dose platinum (mg) | 368 | 604 | 447 | 410 | 368 | 410 |
| Plasma | ||||||
| Cmax (μg/mL) | 25.0 | 21.7 | 27.1 | 23.8 | 19.3 | 18.8 |
| AUC0–inf ((μg h)/mL)a | 63.3 | 57.0 | 59.6 | 74.2 | 41.0 | 53.1 |
| CL (L/h) | 5.81 | 10.6 | 7.50 | 5.53 | 8.98 | 7.72 |
| T1/2z (h) | 4.13 | 4.02 | 4.97 | 5.41 | 4.04 | 4.05 |
| Tumor tissue | ||||||
| Probe recovery (%)b | 44.8 ± 2.5 (41.9–46.3; 3) | 59.9 ± 2.3 (54.6–60.1; 5) | 69.3 ± 1.8 (66.5–71.5; 5) | 75.8 ± 4.4 (70.1–80.5; 5) | 52.2 ± 2.0 (49.6–53.9; 5) | 74.4 ± 4.0 (68.1–77.6; 5) |
| Cmax (μg/mL) | 21.7 | 21.3 | 24.8 | 13.9 | 13.4 | 18.3 |
| AUC0–inf ((μg h)/mL)a | 64.3 | 62.5 | 65.6 | 47.2 | 33.9 | 57.4 |
| T1/2z (h) | 3.64 | 3.85 | 2.70 | 5.68 | 3.71 | 3.08 |
| Adipocytic normal tissue | ||||||
| Probe recovery (%)b | NAc | 25.5 ± 1.2 (24.1–26.9; 4) | 62.9 ± 5.4 (53.8–68.2; 5) | 49.6 ± 2.7 (46.5–53.9; 5) | 17.3 ± 9.9d (10.1–34.5; 5) | 10.8 ± 9.8e (21.1 → 0.4; 5) |
| Cmax (μg/mL) | NA | 25.5 | 19.6 | 12.5 | NA | NA |
| AUC0–inf ((μg h)/mL)a | NA | 83.5 | 51.5 | 52.9 | NA | NA |
| T1/2z (h) | NA | 3.50 | 4.26 | 4.37 | NA | NA |
| Ratio’s | ||||||
| AUC tumor/plama | 1.02 | 1.10 | 1.10 | 0.64 | 0.83 | 1.08 |
| AUC adip. tissue/plasma | NA | 1.46 | 0.86 | 0.71 | NA | NA |
Cmax maximum observed concentration, AUC area under the concentration time curve, CL clearance, T1/2z terminal disposition half-life, NA not available
aCalculated using observed data up to 24 h after start of infusion
bMean ± SD (range; number of observations)
cLeakage of probe observed
dFluctuating and high flow of perfusate
eHighly variable recovery decreasing in subsequent samples