TABLE 3.
Comparisons of the geometric mean plasma and intracranial PK parameters between predicted and observed data in healthy and ALK-positive NSCLC patients.
| PK | Clinical study | Drug | Dosing regimens | N | Subjects | AUC (ng·h/mL, CV%/±SD a ) | Cmax (ng/mL, CV %/±SD) | Ctrough (ng/mL, CV %/±SD) | Prediction/observation ratio | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Prediction | Observation | Prediction | Observation | Prediction | Observation | AUC | Cmax | Ctrough | ||||||
| Plasma | Xu et al. (2014) | CRI b | 250 mg OD | 14 | Healthy | 1968 (46) | 2321 (34) | 115 (43) | 99.6 (28) | - | - | 0.85 | 1.15 | - |
| Kurata et al. (2015) | 500 mg OD | 9 | Patients | 8738 (58) | - | 849 (49) | - | 630 (427–789) | 508.5 (243.5–847.8) | - | - | 1.24 | ||
| Clark et al. (2019) | 50 mg OD | 3 | Patients | 287 (48) | 206 (64) | 31 (42) | 24 (52) | 9 (5–14) | 8 (5–11) | 1.39 | 1.29 | 1.13 | ||
| 100 mg OD | 4 | 987 (43) | 1087 (37) | 71 (47) | 86 (69) | 26 (14–36) | 31 (24–52) | 0.91 | 0.83 | 0.84 | ||||
| 200 mg OD | 8 | 2473 (51) | 2047 (48) | 165 (48) | 149 (27) | 69 (42–93) | 44 (31–160) | 1.21 | 1.11 | 1.57 | ||||
| 200 mg BID | 4 | 2915 (51) | 1780 (61) | 290 (46) | 189 (48) | 205 (134–263) | 158 (132–183) | 1.64 | 1.53 | 1.30 | ||||
| 250 mg BID | 4 | 3820 (45) | 3084 (32) | 378 (46) | 327 (25) | 271 (178–344) | 259 (159–356) | 1.24 | 1.16 | 1.05 | ||||
| 300 mg BID | 5 | 4421 (50) | 4067 (55) | 440 (46) | 420 (48) | 311 (215–396) | 279 (183–403) | 1.09 | 1.05 | 1.11 | ||||
| Xu et al. (2022) | 250 mg OD | 8 | Healthy | 2239 (38) | 2438 (42) | 126 (36) | 118.5 (31) | - | - | 0.92 | 1.06 | - | ||
| Seto et al. (2013) | ALE c | 160 mg BID | 3 | Patients | 2029 ± 736 | 2310 ±598 | 187 ± 69 | 300 ± 104 | 145 ± 52 | 214 ± 34 | 0.88 | 0.62 | 0.68 | |
| 240 mg BID | 3 | 3179 ± 1159 | 2970 ± 937 | 291 ± 107 | 385 ± 100 | 230 ± 82 | 262 ± 115 | 1.07 | 0.76 | 0.88 | ||||
| 300 mg BID | 6 | 4081 ± 1491 | 4970 ± 3260 | 374 ± 137 | 575 ± 322 | 296 ± 106 | 463 ± 369 | 0.82 | 0.65 | 0.64 | ||||
| Gadgeel et al. (2014) | 460 mg BID | 7 | 6629 ± 2427 | 4980 ± 1340 | 604 ± 223 | 618 ± 165 | 486 ± 174 | 460 ± 130 | 1.33 | 0.98 | 1.06 | |||
| 600 mg BID | 5 | 9013 ± 3300 | 5400 ± 1400 | 819 ± 302 | 676 ± 186 | 665 ± 238 | 502 ± 142 | 1.67 | 1.21 | 1.32 | ||||
| 900 mg BID | 7 | 11901 ± 4355 | 9840 ± 4620 | 1078 ± 397 | 1140 ± 448 | 883 ± 315 | 822 ± 444 | 1.21 | 0.95 | 1.07 | ||||
| Morcos et al. (2016) | 600 mg OD | 6 | Healthy | 5916 (31) | 6090 (13) | 223 (25) | 175 (11) | - | - | 0.97 | 1.27 | - | ||
| Morcos et al. (2017) | 48 | 5757 ± 874 | 4360 ± 1160 | 215 ± 55 | 204 ± 57 | - | - | 1.32 | 1.05 | - | ||||
| Morcos et al. (2018) | 24 | 5213 ± 698 | 3180 ± 876 | 193 ± 46 | 169 ± 47 | - | - | 1.64 | 1.14 | - | ||||
| M4 | 600 mg BID | 48 | Healthy | 2205 ± 796 | 1890 ± 477 | 80 ± 23 | 65 ± 17 | - | - | 1.17 | 1.23 | - | ||
| 24 | 2756 ± 994 | 3480 ± 758 | 85 ± 31 | 126 ± 32 | - | - | 0.79 | 0.67 | - | |||||
| Shaw et al. (2017) | LOR b | 10 mg OD | 2 | Patients | 913 (42) | 820 d | 69 (44) | 74d | 26 (21) | - | 1.11 | 0.93 | - | |
| 25 mg OD | 3 | 2547 (41) | 1708 (29) | 156 (31) | 138 (35) | 53 (39) | - | 1.49 | 1.13 | - | ||||
| 50 mg OD | 3 | 3479 (36) | 3487 (41) | 293 (23) | 360 (27) | 88 (22) | - | 1.00 | 0.81 | - | ||||
| 75 mg OD | 11 | 4894 (42) | 4117 (55) | 337 (21) | 422 (50) | 119 (28) | - | 1.19 | 0.80 | - | ||||
| 100 mg OD | 14 | 5611 (48) | 5065 (32) | 559 (28) | 569 (32) | 150 (55) | - | 1.11 | 0.98 | - | ||||
| 150 mg OD | 2 | 6515 (41) | 6185 d | 825 (27) | 638 d | 206 (46) | - | 1.05 | 1.29 | - | ||||
| 200 mg OD | 2 | 12011 (58) | 7856 d | 1101 (32) | 1042 d | 272 (32) | - | 1.53 | 1.06 | - | ||||
| Stypinski et al. (2020) | 100 mg OD | 6 | Healthy | 9166 (41) | 7600 (26) | 526 | 600 (18) | - | - | 1.21 | 0.88 | - | ||
| Hibma et al. (2022) | 11 | 8632 (36) | 8289 (34) | 442 | 501 (38) | - | - | 1.04 | 0.88 | 1.58 | ||||
| Chen et al. (2021) | 19 | Patients | 7819 (30) | 9088 (35) | 581 (31) | 695 (40) | 158 (31) | 100 (32) | 0.86 | 0.84 | - | |||
| Lin et al. (2022) | 8 | Patients | 7055 (35) | 8329 (33) | 563 (29) | 547 (48) | 152 (28) | - | 1.11 | 0.93 | - | |||
| CSF | Costa et al. (2011) | CRI | 250 mg BID | 1 | patients | 17.0 ± 2.2 | - | 6.7 ± 0.90 | - | 2.0 ± 0.52 | 0.62 | - | - | 3.23 |
| Metro et al. (2016) | ALE | 600 mg BID | 2 | patients | 31.2 ± 6.0 | - | 2.9 ± 0.58 | - | 2.2 ± 0.28 | 1.40 | - | - | 1.57 | |
| Sun, et al. (2022) | LOR | 100 mg OD | 4 | patients | 2784 ± 360 | - | 218 ± 22.3 | - | 63.0 ± 11.1 | 86.5 ± 36.8 | - | - | 0.73 | |
a
CV %, percentage coefficient of variation; SD, standard deviation.
b
Geometric mean values are shown.
c
Arithmetic mean values are shown.
d
Not reported data.