Table 1.
Parameter Estimates From the Final PK Model: (A) Primary Parameters and (B) Secondary Parameters
| A. Primary Parameters | ||||
|---|---|---|---|---|
| Parameter | Estimate | % RSE | 95%CI | |
| CL (mL/day) | θ1 | 216 | 1.2 | 211–221 |
| V2 (L) | θ2 | 4.5 | 1.6 | 4.4–4.7 |
| Q (mL/day) | θ3 | 274 | 2.2 | 262–285 |
| V3 (L) | θ4 | 2.8 | 1.7 | 2.7–2.9 |
| VM (mg/L/day) | θ5 | 1.9 | 1.0 | 1.8–1.9 |
| KM (μg/mL) | θ6 | 0.34 | 2.5 | 0.33–0.36 |
| ka (1/day) | θ7 | 0.23 | 2.7 | 0.22–0.25 |
| FSC | θ8 | 0.80 | 1.1 | 0.79–0.81 |
| B. Secondary Parametersa (Mean ± SD) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| 162 mg SC QW | 162 mg SC Q2W | 8 mg/kg IV Q4W | |||||||
| Tocilizumab Dose | First Dosing Interval | Steady State | RAC | First Dosing Interval | Steady State | RAC | First Dosing Interval | Steady State | RAC |
| AUCτ, μg·h/mL | 1243 ± 689 | 8254 ± 3833 | 6.8 | 1210 ± 940 | 3460 ± 2530 | 2.7 | 28 824 ± 7704 | 39 216 ± 14 304 | 1.36 |
| Cmax, μg/mL | 9.3 ± 5.1 | 51.3 ± 23.2 | 5.5 | 5.8 ± 4.1 | 13 ± 8.3 | 2.1 | 136 ± 34 | 154 ± 42 | 1.13 |
| Ctrough, μg/mL | 7.0 ± 4.1 | 45.3 ± 22.2 | 6.4 | 1.0 ± 1.5 | 5.9 ± 6.3 | 5.6 | 7.7 ± 6.7 | 18.7 ± 15.3 | 2.43 |
CL, linear clearance; V2, central volume of distribution; Q, intercompartmental clearance; V3, peripheral volume of distribution; VM, maximum target‐mediated elimination rate; KM, Mechaelis–Menten constant; Ka, absorption rate constant; FSC, absolute bioavailability following SC dosing; RSE, relative standard error, RSE, 100·SE/parameter estimate; 95%CI, 95% confidence interval; AUCτ, area under the concentration curve within the dosing interval; Cmax, maximum concentration; Ctrough, predose trough concentration; PK, pharmacokinetic; Q2W, every 2 weeks; QW, weekly; RAC, accumulation ratio; SC, subcutaneous.
Data are from simulations performed for 5000 subjects.