TABLE 3.
Raxibacumab PKs in rabbits administered 3 daily intragastric 50-mg/kg LVX doses alone or in combination with a single i.v. 40-mg/kg raxibacumab dosea
| Parameter | Mean | CV | Mean ± SD valueb |
|---|---|---|---|
| Primary parameters | |||
| V1 (ml) | 112.17 (1.9)c | 10.8 (26.6) | |
| CL (ml/day) | 28.12 (5.5) | 27.5 (31.0) | |
| V2 (ml) | 60.22 (7.5) | 20.6 (87.8) | |
| CLD2 (ml/day) | 73.62 (10.6) | 27.6 (61.9) | |
| Secondary parameters | |||
| Cmax (μg/ml) | 1,114 ± 138 | ||
| AUC0–∞ (μg · day/ml) | 4,590 ± 1,106 | ||
| t1/2α (days) | 0.36 ± 0.05 | ||
| t1/2β (days) | 4.67 ± 1.10 | ||
| MRT (days) | 6.40 ± 1.63 | ||
| Vss (ml/kg) | 56.00 ± 5.74 |
The residual variability was the coefficient of variation of 6.2 (relative standard error [RSE], 51.7) for the proportional error component and SD of 45.5 μg/ml (RSE, 41.2 μg/ml) for the additive error component. The effect of weight on CL, in which weight was normalized to the median body weight for the LVX-raxibacumab group (3.12 kg), was calculated as CL × (weight/3.12)1.743 (RSE, 42.1), with CL for rabbits with weights of 2.75, 3.12, and 3.55 kg being 22.56, 28.12, and 35.21 ml/day, respectively. CV, coefficient of variation; V1, volume of distribution for the central compartment; CL, clearance; V2, volume of distribution for the peripheral compartment; CLD2, intercompartmental clearance; Cmax, maximum plasma drug concentration; AUC0–∞, area under the plasma drug concentration-time curve from time zero to infinite time; t1/2α, elimination half-life for the 1st phase; t1/2β, elimination half-life for the 2nd (terminal) phase; MRT, mean residence time; Vss, volume of distribution at steady state.
Based on the post hoc estimates for the individual rabbits.
Values in parentheses represent the relative standard error of the estimate (in percent).