Table 3 Comparisons of covariate-adjusted mean values of PK features of VRC07-523LS between single and combination administrations via the TMLE method

CL (L/day)

Clearance from the central compartment

0.13 (0.12, 0.13)

0.12 (0.11, 0.13)

1.06 (1.00, 1.13)

0.06

0.22

Vc (L)

Volume of the central compartment

4.66 (4.07, 5.34)

3.74 (3.26, 4.29)

1.25 (1.14, 1.37)

< 0.001

< 0.001

Q (L/day)

Inter-compartmental distribution clearance

0.30 (0.22, 0.41)

0.30 (0.22, 0.41)

1.00 (0.91, 1.11)

0.97

1.00

Vp (L)

Volume of the peripheral compartment

3.89 (3.45, 4.38)

3.51 (3.07, 4.01)

1.11 (1.04, 1.18)

< 0.001

0.007

Distribution half-life (day)

Length of time for serum concentration of the mAb to decrease by half in the distribution phase

4.23 (3.15, 5.69)

3.71 (2.75, 5.01)

1.14 (1.03, 1.27)

0.01

0.086

Elimination half-life (day)

Length of time for serum concentration of the mAb to decrease by half in the elimination phase

52.84 (50.17, 55.66)

47.67 (45.46, 49.98)

1.11 (1.05, 1.17)

< 0.001

0.002

Dose normalized steady-state AUC (day/L)

Dose-normalized area under the curve in steady state after IV administration of 1.4 g

7.94 (7.52, 8.39)

8.42 (7.96, 8.9)

0.94 (0.89, 1)

0.06

0.224

Predicted concentrations at 1 day (mcg/ml)

Post 1.4 g IV infusion

271.34 (244.02, 301.71)

332.68 (299.8, 369.17)

0.82 (0.75, 0.88)

< 0.001

< 0.001

Predicted concentrations at 4-week (mcg/ml)

Post 1.4 g IV infusion

94.28 (89.34, 99.49)

103.99 (98.15, 110.18)

0.91 (0.86, 0.96)

< 0.001

0.004

Predicted concentrations at 8-week (mcg/ml)

Post 1.4 g IV infusion

61.75 (58.02, 65.71)

66.73 (62.81, 70.89)

0.93 (0.87, 0.99)

0.02

0.091

Predicted concentrations at 16-week (mcg/ml)

Post 1.4 g IV infusion

28.86 (26.78, 31.11)

29.06 (26.96, 31.33)

0.99 (0.91, 1.08)

0.88

1.00