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Table 5 Pharmacokinetics parameters by dose levels following single and double doses of belimumab

From: Biologic activity and safety of belimumab, a neutralizing anti-B-lymphocyte stimulator (BLyS) monoclonal antibody: a phase I trial in patients with systemic lupus erythematosus

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
  1. Belimumab was given as a 2-hour infusion. Cohorts 1 to 4 received single doses of belimumab. Cohorts 5 to 8 received two doses of belimumab 21 days apart. In the double dose cohorts, patients who missed doses or displayed positive immunogenicity were excluded. aOne patient in Cohort 1 was anti-belimumab antibody positive on days 14, 28, 56, and 84, and the data were, therefore, excluded from the mean calculation. bOne patient in Cohort 4 did not receive a full dose secondary to urticarial reaction, and serum concentration data from this patient were excluded from the PK analysis. AUC0-∞, area under the serum drug concentration-time curve from time 0 to infinite time; AUC0-∞ /dose, dose-normalized AUC0-∞ ; CL, clearance; Cmax, maximum serum drug concentration; Cmax/dose, dose-normalized Cmax; MRT, mean residence time; SD, standard deviation; t1/2,α, elimination half-life for the distribution phase; t1/2,β, elimination half-life for the terminal phase; V1, volume of distribution for the central compartment; Vss, volume of distribution at steady state.