Pharmacokinetic parameter (mean ± SD) | Belimumab dose and number of patients per cohort | |||||||
---|---|---|---|---|---|---|---|---|
 | Cohort 1 (1.0 mg/kg; n = 7)a | Cohort 2 (4.0 mg/kg; n = 7) | Cohort 3 (10 mg/kg; n = 7) | Cohort 4 (20 mg/kg; n = 6)b | Cohort 5 (1.0 mg/kg; n = 6) | Cohort 6 (4.0 mg/kg; n = 7) | Cohort 7 (10 mg/kg; n = 7) | Cohort 8 (20 mg/kg; n = 6) |
Cmax (μg/ml) | 22.3 ± 4.2 | 81.2 ± 24.6 | 192.4 ± 34.9 | 523.9 ± 293.7 | 20.6 ± 3.0 | 105.4 ± 28.0 | 240.7 ± 41.7 | 368.1 ± 93.5 |
Cmax/dose (kg/ml) | 0.0223 ± 0.0042 | 0.0203 ± 0.0061 | 0.0192 ± 0.0035 | 0.0262 ± 0.0147 | 0.0206 ± 0.0030 | 0.0264 ± 0.0070 | 0.0241 ± 0.0042 | 0.0184 ± 0.0047 |
AUC0-∞ (day·μg/ml) | 156 ± 46 | 629 ± 258 | 1,510 ± 315 | 3,384 ± 1,424 | 148 ± 30 | 729 ± 145 | 1,849 ± 355 | 3,221 ± 781 |
AUC0-∞ /dose (day· kg/ml) | 0.1561 ± 0.0456 | 0.1572 ± 0.0646 | 0.1510 ± 0.0315 | 0.1692 ± 0.0712 | 0.1477 ± 0.0301 | 0.1822 ± 0.0363 | 0.1849 ± 0.0355 | 0.1611 ± 0.0391 |
t1/2,α (day) | 0.96 ± 0.61 | 1.49 ± 0.76 | 1.84 ± 0.89 | 1.27 ± 0.43 | 1.87 ± 0.99 | 1.23 ± 0.65 | 1.03 ± 0.48 | 2.21 ± 1.84 |
t1/2,β (day) | 8.46 ± 2.21 | 9.88 ± 2.18 | 10.63 ± 2.89 | 11.34 ± 3.02 | 9.67 ± 1.33 | 9.91 ± 2.99 | 9.64 ± 2.20 | 14.13 ± 5.31 |
V1 (ml/kg) | 44.90 ± 7.12 | 52.69 ± 18.59 | 52.91 ± 10.20 | 53.17 ± 40.89 | 48.95 ± 8.26 | 39.61 ± 11.00 | 41.83 ± 7.63 | 56.60 ± 15.02 |
Vss (ml/kg) | 73.29 ± 13.64 | 82.33 ± 22.31 | 86.30 ± 16.77 | 111.67 ± 95.72 | 76.45 ± 19.64 | 69.82 ± 22.72 | 69.21 ± 13.59 | 102.11 ± 30.40 |
CL (ml/day per kg) | 7.15 ± 3.18 | 7.20 ± 2.48 | 6.90 ± 1.57 | 7.33 ± 4.38 | 7.00 ± 1.38 | 5.68 ± 1.11 | 5.57 ± 1.02 | 6.52 ± 1.54 |
MRT (day) | 11.13 ± 3.08 | 12.18 ± 3.22 | 13.03 ± 3.59 | 14.01 ± 4.17 | 10.97 ± 1.86 | 12.47 ± 4.07 | 12.65 ± 2.66 | 16.06 ± 4.15 |