Table 5

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

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)

C_max (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

C_max/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

AUC_0-∞ (day·μg/ml)

156 ± 46

629 ± 258

1,510 ± 315

3,384 ± 1,424

148 ± 30

729 ± 145

1,849 ± 355

3,221 ± 781

AUC_0-∞ /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

t_1/2,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

t_1/2,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

V_ss (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

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. AUC_0-∞, area under the serum drug concentration-time curve from time 0 to infinite time; AUC_0-∞ /dose, dose-normalized AUC_0-∞ ; CL, clearance; C_max, maximum serum drug concentration; C_max/dose, dose-normalized C_max; MRT, mean residence time; SD, standard deviation; t_1/2,α, elimination half-life for the distribution phase; t_1/2,β, elimination half-life for the terminal phase; V₁, volume of distribution for the central compartment; V_ss, volume of distribution at steady state.

Furie et al. Arthritis Research & Therapy 2008 10:R109   doi:10.1186/ar2506