Table 2:
Final Population PK Model Parameters and Bootstrap Estimate
| Final Parameter | Standard Error | Bootstrap Estimates* (Median and 95% CI) | |
|---|---|---|---|
| Θ1 (VI) | 3.66 | 0.064 | 3.67 (3.55 – 3.78) |
| Θ2 (CL) | 0.214 | 0.00816 | 0.216 (0.20 – 0.23) |
| Θ3 (V2) | 3.13 | 0.088 | 3.14 (2.97 – 3.31) |
| Θ4 (Q) | 0.624 | 0.0456 | 0.62 (0.55 – 0.72) |
| Θ5 (Albumin CL) | −0.84 | 0.17 | −0.86 (−1.14 - −0.53) |
| Θ6 (Weight Vss) | 0.65 | 0.056 | 0.64 (0.54 – 0.75) |
| Θ7 (Albumin Vss) | −0.35 | 0.11 | −0.32 (−0.53 - −0.15) |
| Θ8 (HV on Vss) | 0.83 | 0.025 | 0.82 (0.78 – 0.87) |
| Θ9 (SMM on Vss) | 0.77 | 0.025 | 0.77 (0.72 – 0.83) |
| Θ10 (HV on CL) | 0.77 | 0.041 | 0.77 (0.70 – 0.83) |
| Θ11 (ALT CL) | −0.096 | 0.041 | −0.097 (−0.18 - −0.013) |
| Θ12 (SCR Vss) | 0.16 | 0.051 | 0.15 (0.062 – 0.25) |
| Θ13 (CD on CL) | 1.24 | 0.081 | 1.24 (1.11 – 1.45) |
| Variability (η) | |||
| Between-subject (CL) | 20.0% | 0.11% | 19.9% (17.8% - 22.1%) |
| Between-subject (Vss) | 42.0% | 1.71% | 41.0% (37.8% - 44.5%) |
| Error (ε) | |||
| Proportional | 22.4% | 0.79% | 22.2% (20.8% - 23.8%) |
| Additive | 0.0217 | 0.0028 | 0.022 (0.0005 – 0.056) |
*
Bootstrap successfully converged 98.9%
Abbreviations: ALB=albumin, ALT=alanine aminotransferase, CD=Castleman’s disease, CL=clearance, HV=healthy volunteers, SCR= serum creatinine, SMM=smoldering multiple myeloma, V1=central volume of distribution, V2=peripheral volume of distribution, Vss=covariate assessed on both V1 and V2
CL (L/day) = 0.214 x (ALB/4.1)−0.84 x (0.77 if HV) x (ALT/17)−0.096 x (1.24 if CD)
Vss (L) = (3.66 + 3.13) x (WT/73)0.65 x (ALB/4.1)−0.35 x (0.83 if HV) x (0.77 if SMM) x (SCR/0.894)0.16