Table 3.
Bortezomib geometric mean (SD) peripheral blood plasma (PL) and peritoneal fluid (PF) pharmacokinetic parameters.
| Dose (mg/m2) | Peritoneal fluid | Plasma | PF/PL-ratio | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
|
|
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| Cmax (μg/mL) | Tmax (min) | AUC0 – t (μg/mL·min) | AUC0 – infa (μg/mL·min) | t½ (min) | Cl/F (mL/h/m2) | Vss/F (mL/m2) | Cmax (ng/mL) | Tmax (min) | AUC0 – t (μg/mL·min) | t½ (min) | Cmax | AUC0 – t | |
| 0.5 (N = 9) | 0.86 (0.33) | 44 (19) | 55 (32) | 57 (34) | 46 (62) | 524 (452) | 695 (453) | 1.59 (1.14) | 94 (48) | 0.27 (0.18) | 210 (85) | 586 (525) | 224 (204) |
| 0.9 (N = 4) | 1.62 (0.62) | 43 (31) | 125 (30) | 140 (58) | 153 (182) | 385 (127) | 744 (277) | 2.33 (4.44) | 81 (67) | 0.45 (0.50) | 296 (169) | 633 (1280) | 271 (853) |
| 1.3 (N = 3) | 1.07 (1.31) | 60 (24) | 88 (104) | 88 (104) | 10 (2) | 884 (2337) | 988 (3532) | 7.13 (3.76) | 73 (14) | 1.04 (0.44) | 192 (225) | 150 (172) | 85 (141) |
| 1.7 (N = 3) | 1.21 (1.89) | 50 (25) | 126 (116) | 127 (115) | 47 (18) | 804 (1091) | 1354 (4814) | 12.4 (0.7) | 73 (10) | 1.83 (0.34) | 122 (12) | 98 (163) | 69 (83) |
| 2.1 (N = 3) | 4.03 (0.99) | 43 (13) | 246 (138) | 258 (136) | 95 (20) | 488 (269) | 769 (954) | 17.7 (2.5) | 70 (25) | 2.89 (0.53) | 135 (47) | 228 (87) | 85 (62) |
| 2.5 (N = 4) | 3.27 (1.98) | 70 (27) | 222 (154) | 298 (195) | 52 (151) | 503 (555) | 1041 (1036) | 16.9 (11.8) | 105 (35) | 2.46 (2.43) | 113 (40) | 164 (147) | 87 (110) |
| All (N = 26) | – | 50 (23) | – | – | 51 (109) | 547 (876) | 850 (1922) | – | 86 (43) | – | 179 (128) | 304 (665) | 139 (366) |
SD, standard deviation; Cmax, peak drug concentration; Tmax, time to peak concentration; t1/2, elimination half-life; Cl/F, apparent total clearance of the drug from plasma; Vss/F, apparent volume of distribution at steady state.
a
mean extrapolated portion represented 6.3% of AUC0 – inf (range 0.004–75.6%).