Pharmacokinetic parameters of 3 different ATLG doses
| ATLG dose . | Cmax (ug/mL) . | AUC0-tlast (d × ug/mL) . | AUC0-∞ (d × ug/mL) . | AUCpre (d × ug/mL) . | AUCpost (d × ug/mL) . | Ctransplantation (ug/mL) . | AUCexpol% (%) . | tmax (d) . | T1/2 (d) . | Cl (l/d/kg) . | Vz (l/kg) . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 15 mg/kg | |||||||||||
| N | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
| Mean | 9.386 | 42.214 | 46.940 | 36.148 | 10.792 | 1.144 | 9.522 | –8.000 | 5.484 | 0.348 | 2.671 |
| SD | 3.949 | 13.907 | 15.244 | 11.291 | 4.876 | 0.534 | 8.133 | 0.707 | 1.162 | 0.115 | 0.817 |
| Min | 3.60 | 27.77 | 29.02 | 20.65 | 5.68 | 0.28 | 4.31 | –9.00 | 3.62 | 0.22 | 2.02 |
| Max | 14.20 | 64.51 | 69.18 | 51.33 | 17.85 | 1.70 | 23.86 | –7.00 | 6.47 | 0.52 | 4.04 |
| Geometric mean | 8.543 | 40.546 | 44.970 | 34.620 | 9.953 | 0.981 | 7.670 | 5.371 | 0.334 | 2.585 | |
| 30 mg/kg | |||||||||||
| N | 9 | 9 | 9 | 9 | 9 | 7 | 9 | 9 | 9 | 9 | 9 |
| Mean | 22.100 | 111.726 | 131.387 | 96.338 | 35.049 | 2.989 | 15.971 | –8.000 | 7.083 | 0.283 | 2.972 |
| SD | 13.861 | 64.234 | 73.025 | 55.821 | 21.773 | 1.965 | 7.864 | 0.000 | 2.874 | 0.124 | 1.932 |
| Min | 10.10 | 47.87 | 60.35 | 40.84 | 8.11 | 1.35 | 3.01 | –8.00 | 3.11 | 0.10 | 0.88 |
| Max | 54.03 | 250.92 | 290.86 | 221.26 | 70.04 | 7.00 | 26.94 | –8.00 | 13.43 | 0.50 | 6.91 |
| Geometric mean | 19.141 | 97.847 | 116.896 | 84.556 | 29.188 | 2.569 | 13.559 | 6.607 | 0.257 | 2.446 | |
| 60 mg/kg | |||||||||||
| N | 4 | 4 | 4 | 4 | 4 | 3 | 4 | 4 | 4 | 4 | 4 |
| Mean | 57.500 | 372.792 | 412.607 | 285.649 | 126.957 | 12.097 | 8.731 | –8.000 | 7.891 | 0.173 | 2.228 |
| SD | 16.718 | 145.633 | 170.515 | 99.069 | 74.583 | 9.350 | 3.887 | 0.816 | 2.775 | 0.092 | 2.058 |
| Min | 32.48 | 185.56 | 196.11 | 153.30 | 42.81 | 3.86 | 5.38 | -9.00 | 5.95 | 0.10 | 1.02 |
| Max | 67.39 | 525.93 | 582.93 | 365.12 | 217.81 | 22.26 | 13.78 | –7.00 | 11.99 | 0.31 | 5.29 |
| Geometric mean | 55.173 | 347.665 | 381.188 | 270.246 | 108.042 | 9.560 | 8.117 | 7.581 | 0.157 | 1.722 |
| ATLG dose . | Cmax (ug/mL) . | AUC0-tlast (d × ug/mL) . | AUC0-∞ (d × ug/mL) . | AUCpre (d × ug/mL) . | AUCpost (d × ug/mL) . | Ctransplantation (ug/mL) . | AUCexpol% (%) . | tmax (d) . | T1/2 (d) . | Cl (l/d/kg) . | Vz (l/kg) . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 15 mg/kg | |||||||||||
| N | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
| Mean | 9.386 | 42.214 | 46.940 | 36.148 | 10.792 | 1.144 | 9.522 | –8.000 | 5.484 | 0.348 | 2.671 |
| SD | 3.949 | 13.907 | 15.244 | 11.291 | 4.876 | 0.534 | 8.133 | 0.707 | 1.162 | 0.115 | 0.817 |
| Min | 3.60 | 27.77 | 29.02 | 20.65 | 5.68 | 0.28 | 4.31 | –9.00 | 3.62 | 0.22 | 2.02 |
| Max | 14.20 | 64.51 | 69.18 | 51.33 | 17.85 | 1.70 | 23.86 | –7.00 | 6.47 | 0.52 | 4.04 |
| Geometric mean | 8.543 | 40.546 | 44.970 | 34.620 | 9.953 | 0.981 | 7.670 | 5.371 | 0.334 | 2.585 | |
| 30 mg/kg | |||||||||||
| N | 9 | 9 | 9 | 9 | 9 | 7 | 9 | 9 | 9 | 9 | 9 |
| Mean | 22.100 | 111.726 | 131.387 | 96.338 | 35.049 | 2.989 | 15.971 | –8.000 | 7.083 | 0.283 | 2.972 |
| SD | 13.861 | 64.234 | 73.025 | 55.821 | 21.773 | 1.965 | 7.864 | 0.000 | 2.874 | 0.124 | 1.932 |
| Min | 10.10 | 47.87 | 60.35 | 40.84 | 8.11 | 1.35 | 3.01 | –8.00 | 3.11 | 0.10 | 0.88 |
| Max | 54.03 | 250.92 | 290.86 | 221.26 | 70.04 | 7.00 | 26.94 | –8.00 | 13.43 | 0.50 | 6.91 |
| Geometric mean | 19.141 | 97.847 | 116.896 | 84.556 | 29.188 | 2.569 | 13.559 | 6.607 | 0.257 | 2.446 | |
| 60 mg/kg | |||||||||||
| N | 4 | 4 | 4 | 4 | 4 | 3 | 4 | 4 | 4 | 4 | 4 |
| Mean | 57.500 | 372.792 | 412.607 | 285.649 | 126.957 | 12.097 | 8.731 | –8.000 | 7.891 | 0.173 | 2.228 |
| SD | 16.718 | 145.633 | 170.515 | 99.069 | 74.583 | 9.350 | 3.887 | 0.816 | 2.775 | 0.092 | 2.058 |
| Min | 32.48 | 185.56 | 196.11 | 153.30 | 42.81 | 3.86 | 5.38 | -9.00 | 5.95 | 0.10 | 1.02 |
| Max | 67.39 | 525.93 | 582.93 | 365.12 | 217.81 | 22.26 | 13.78 | –7.00 | 11.99 | 0.31 | 5.29 |
| Geometric mean | 55.173 | 347.665 | 381.188 | 270.246 | 108.042 | 9.560 | 8.117 | 7.581 | 0.157 | 1.722 |
AUC0-∞, AUC from the time of dosing extrapolated to infinity, based on the last observed concentration; AUC0-tlast, area under the curve (AUC) from the time of dosing (day –12) to the last measurable concentration; AUCexpol%, percentage of AUC0-∞ due to extrapolation from tlast to infinity; AUCpost, AUC from the day of transplant (day 0) to the last measurable concentration;AUCpre, AUC from the time of dosing until day of transplant (day 0); Cl, total body clearance for intravenous administration = dose/AUC0-∞; Cmax, maximum observed concentration; Ctransplantation, concentration at day of transplant (day 0); T1/2, apparent terminal half-life associated with the terminal (log-linear) portion of the curve as estimated by linear regression of time vs log concentration curve T1/2 = 0.693/λz; tmax, time of maximum observed concentration; SD, standard deviation; Vz, volume of distribution based on the terminal phase = Cl/λz.