Table 5. Pharmacokinetic parameters of bortezomib and docetaxel by dose level.
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All values shown as mean (%CV)
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|---|---|---|---|---|---|---|---|---|---|
| Day | C0 (ng ml−1) | AUC0–t (h ng ml−1) | AUC0–∞∞ (h ng ml−1) | T½,z (h) | T½,z 24-h (h) | CL (l h−1) | Vss (l) | Vz (l) | |
| Bortezomib dose (mg m −2 ) | |||||||||
| 1.0 (n=5) | 1 | 208 (34) | 43.0 (38) | 54.6 (31) | 9.15 (64) | 15.1 (n=2) | 33.7 (30) | 222 (75) | 408 (63) |
| 1.3 (n=3) | 1 | 137 (54) | 35.5 (31) | 49.0 (28) | 14.2 (47) | 18.1 (n=2) | 51.0 (38) | 596 (45) | 924 (26) |
| 1.5 (n=8) | 1 | 268 (71) | 69.0 (43) | 85.3 (51) | 6.9 (99) | 17.8 (n=2) | 36.9 (57) | 209 (68) | 282 (77) |
| 1.0 (n=5) | 11 | 552 (148) | 112 (32) | 133 (24) | 12.2 (32) | 14.3 (n=4) | 13.5 (25) | 151 (49) | 237 (46) |
| 1.3 (n=3) | 11 | 237 (59) | 90.5 (27) | 111 (18) | 12.2 (73) | 17.1 (n=2) | 21.0 (11) | 237 (96) | 374 (78) |
| 1.5 (n=6) | 11 | 153 (41) | 103 (25) | 161 (31) | 23.6 (36) | 23.6 | 16.0 (23) | 391 (47) | 538 (42) |
| Docetaxel dose (mg m −2 ) | |||||||||
| Cmax (ng ml−1) | AUC0–t (h ng ml−1) | AUC0–∞∞ (h ng ml−1) | T½,z (h) | T½,z 24-h (h) | CL (l h−1) | Vss (l) | Vz (l) | ||
| 75 (n=7) | 1 | 1620 (38) | 1704 (50) | 1847 (54) | 10.4 (86) | 17.6 (n=3) | 85.2 (47) | 180 (72) | 920 (33) |
| 100 (n=6) | 1 | 2522 (51) | 2547 (36) | 2731 (34) | 15.0 (42) | 17.4 (n=5) | 69.6 (31) | 372 (85) | 1514 (55) |
C0=back-extrapolated time 0 plasma drug concentration (bortezomib alone); Cmax=observed maximum plasma drug concentration (docetaxel alone); AUC0−t=area under plasma concentration time curve from time 0 to last time point with measurable drug concentration; AUC0−∞=area under plasma concentration time curve extrapolated to infinity; T½,z=apparent plasma half-life; T½,z (24-h)=apparent plasma half-life in patients with measurable plasma concentrations at 24 h post-dose; CL=total body clearance; CV=coefficient of variance; Vss=volume of distribution at steady state; Vz=apparent volume of distribution in terminal elimination phase.