Mean ± SEM whole blood concentrations of rhTNF (ng/mL) following infusion with various dose levels of CYT-6091
| Time, min | Dose administered, μg/m2 | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| 50 | 100 | 150 | 200 | 250 | 300 | 400 | 500 | 600 | |
| 5 | 7.7 ± 0.1 | 17.2 ± 2.6 | 25.2 ± 1.3 | 47.6 ± 5.8 | 58.2 ± 16.4 | 62.6 ± 12.1 | 85.1 ± 11.9 | 106.7 ± 9.7 | 154.7 ± 34.7 |
| 15 | 5.2 ± 0.7 | 10.1 ± 1.5 | 16.5 ± 1.0 | 34.2 ± 5.6 | 43.8 ± 9.7 | 48.1 ± 13.6 | 74.9 ± 13.4 | 73.8 ± 15.8 | 147.5 ± 22.8 |
| 30 | 4.0 ± 0.6 | 6.8 ± 1.0 | 11.4 ± 1.9 | 25.9 ± 6.9 | 24.4 ± 4.8 | 33.3 ± 9.8 | 58.4 ± 12.2 | 60.0 ± 16.2 | 109.2 ± 16.1 |
| 60 | 2.5 ± 0.4 | 3.5 ± 0.3 | 6.5 ± 1.2 | 15.5 ± 4.7 | 21.7 ± 2.8 | 21.3 ± 6.7 | 46.5 ± 4.6 | 43.3 ± 13.3 | 90.2 ± 12.7 |
| 120 | 1.3 ± 0.3 | 1.7 ± 0.1 | 3.2 ± 0.7 | 8.4 ± 2.9 | 10.9 ± 1.5 | 10.9 ± 4.0 | 21.7 ± 4.5 | 24.6 ± 8.3 | 47.2 ± 3.4 |
| 180 | 0.9 ± 0.2 | 1.1 ± 0.1 | 1.8 ± 0.4 | 4.6 ± 1.3 | 4.7 ± 0.6 | 4.3 ± 1.4 | 11.8 ± 3.8 | 12.2 ± 3.8 | 24.0 ± 1.8 |
| 240 | 0.6 ± 0.1 | 0.7 ± 0.1 | 1.3 ± 0.3 | 3.1 ± 0.9 | 2.6 ± 0.4 | 2.4 ± 0.8 | 6.1 ± 1.6 | 8.9 ± 3.0 | 12.3 ± 1.1 |
| 480 | 0.2 ± 0.1 | 0.2 ± 0.0 | 0.4 ± 0.2 | 1.0 ± 0.2 | 0.8 ± 0.0 | 0.8 ± 0.4 | 1.6 ± 0.5 | 2.6 ± 0.6 | 2.6 ± 0.0 |
| 1,440 | BDL | BDL | BDL | BDL | BDL | BDL | 0.3 ± 0.1 | 1.2 ± 0.1 | 0.6 ± 0.0 |
| Analysis (mean ± SD) of the pharmacokinetic parameters of CYT-6091 in man | |||||||||
| Dose of CYT-6091, μg/m2 | Total dose, μg | C max, ng/mL | Terminal half-life, min | AUC, min × ng/mL | Volume of distribution, mL | Clearance, mL/min | |||
| 50 | 90 ± 5 | 7.7 ± 0.2 | 120.7 ± 19.6 | 611 ± 192 | 18,686 ± 2,988 | 155 ± 40 | |||
| 100 | 202 ± 33 | 17.2 ± 4.6 | 131.3 ± 21.0 | 977 ± 64 | 24,064 ± 8,308 | 209 ± 48 | |||
| 150 | 270 ± 49 | 25.2 ± 2.3 | 127.0 ± 34.4 | 1,575 ± 412 | 18,641 ± 2,845 | 177 ± 67 | |||
| 200 | 314 ± 7 | 47.7 ± 9.9 | 146.3 ± 22.2 | 3,789 ± 1,465 | 12,063 ± 5,174 | 90 ± 28 | |||
| 250 | 410 ± 62 | 58.2 ± 16.4 | 112.7 ± 27.2 | 3,888 ± 890 | 11,355 ± 3,536 | 107 ± 23 | |||
| 300 | 563 ± 45 | 62.6 ± 21.0 | 113.0 ± 46.2 | 4,403 ± 2,223 | 13,241 ± 4,637 | 159 ± 96 | |||
| 400 | 785 ± 148 | 85.1 ± 20.7 | 266.0 ± 79.0 | 9,297 ± 3,845 | 16,265 ± 9,021 | 97 ± 51 | |||
| 500 | 823 ± 153 | 106.7 ± 16.7 | 371.1 ± 133 | 11,206 ± 4,359 | 31,248 ± 27,137 | 84 ± 53 | |||
| 600 | 1,208 ± 214 | 154.7 ± 34.7 | 160.5 ± 52.0 | 17,730 ± 2,928 | 10,865 ± 5,666 | 71 ± 24 | |||
Abbreviation: BDL, below the limit of detection.