Table 3.
Primary and secondary parameters of total paclitaxel PK obtained from the two-compartment model by dose level
| Dose levela | All data sets (n = 25) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| 150 mg/m2 (n = 2) | 175 mg/m2 (n = 3) | 200 mg/m2 (n = 4) | 225 mg/m2 (n = 4) | 250 mg/m2 (n = 5) | 275 mg/m2 (n = 6) | Median (min–max) | Mean ± SD | ||
| Primary PK parametersb | |||||||||
| Vc (L/m2) | 16.9 (11.9–21.8) | 13.9 (12.5–16.5) | 15.4 (8.7–21.9) | 17.7 (9.8–23.7) | 13.7 (8.2–20.3) | 12.8 (11.0–19.3) | 13.7 (6.9–23.7) | 14.8 ± 4.9 | |
| K10 (h–1) | 0.93 (0.92–0.93) | 1.05 (0.86–1.13) | 0.85 (0.62–1.06) | 0.56 (0.31–2.31) | 1.21 (0.77–1.40) | 0.95 (0.46–1.24) | 0.93 (0.31–2.31) | 0.96 ± 0.40 | |
| K12 (h–1) | 0.43 (0.36–0.50) | 0.38 (0.29–0.61) | 0.32 (0.16–0.60) | 0.36 (0.11–1.12) | 0.67 (0.44–2.08) | 0.40 (0.28–0.62) | 0.42 (0.11–2.08) | 0.53 ± 0.42 | |
| K21 (h–1) | 0.13 (0.12–0.14) | 0.13 (0.11–0.13) | 0.11 (0.04–0.33) | 0.13 (0.04–0.26) | 0.15 (0.14–0.28) | 0.16 (0.13–0.21) | 0.14 (0.04–0.33) | 0.15 ± 0.07 | |
| Secondary PK parametersc | |||||||||
| Cmax (ng/mL) | 5354 (3893–6815) | 7264 (5220–7609) | 7713 (5198–13,716) | 7746 (5363–12,863) | 8692 (3183–9589) | 10,398 (8227–15,466) | – | – | |
| AUCinf (ng h/mL) | 10,551 (7416–13,686) | 12,367 (10,063–14,666) | 15,396 (14,145–23,571) | 22,979 (9951–51,154) | 15,985 (14,632–24,945) | 17,783 (15,932–48,203) | – | – | |
| t1/2α (h) | 0.50 (0.47–0.52) | 0.45 (0.40–0.59) | 0.55 (0.46–0.71) | 0.93 (0.20–1.63) | 0.33 (0.20–0.51) | 0.52 (0.36–0.84) | 0.47 (0.20–1.63) | 0.55 ± 0.32 | |
| t1/2β (h) | 8.04 (7.88–8.20) | 8.93 (7.39–8.96) | 8.83 (4.75–18.47) | 9.75 (4.82–23.07) | 7.16 (6.93–10.80) | 6.76 (5.54–9.40) | 7.72 (4.75–23.10) | 8.83 ± 4.10 | |
| CL (L/h/m2) | 15.6 (11.0–20.2) | 14.2 (11.9–17.3) | 12.7 (8.5–14.1) | 13.0 (4.4–22.6) | 15.6 (10.0–17.1) | 15.5 (5.7–17.3) | 14.1 (4.4–22.6) | 13.4 ± 4.8 | |
| Vz (L/m2) | 182 (125–239) | 182 (127–224) | 165 (93–226) | 140 (125–206) | 165 (104–243) | 145 (62–185) | 155 (62–243) | 155 ± 49 | |
| Vss (L/m2) | 70.4 (54.1–86.7) | 57.4 (44.8–96.6) | 57.2 (41.1–61.7) | 66.9 (50.9–76.0) | 70.0 (50.2–165.0) | 54.5 (31.4–67.9) | 59.8 (23.8–165.0) | 63.3 ± 26.9 | |
Data are presented as median (min–max). n number of data sets
aData at dose level 90 mg/m2 (n = 1) are not shown individually but are included in the last column presenting median (min–max) and mean (SD) values for all data sets
bVc apparent volume of the central compartment, K10 rate constant for elimination from the central compartment, K12 rate constant for drug transport from the central to the peripheral compartment, K21 rate constant for the drug transport from the peripheral to the central compartment
cAUCinf total area under the plasma concentration–time curve to infinite time, Cmax maximum plasma concentration, CL clearance, t1/2α distribution half-life, t1/2β terminal elimination half-life, Vz distribution volume during the terminal elimination phase, Vss distribution volume during steady state