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Table 3 Final parameter estimates and bootstrap outcomes

From: Model-based adaptive phase I trial design of post-transplant decitabine maintenance in myelodysplastic syndrome

Parameter Unit Description Population typical value Between-subject variability
Estimate Bootstrap median (95 % CI) Estimate (as CV%) Bootstrap median (95 % CI)
Pharmacokinetic parameters       
CL L/h·m2 Clearance 87.8 88.3 (72.2–108) 21.4 20.5 (13.0–26.8)
V c L/m2 Volume of central compartment 18.5 18.2 (14.2–23.5) NE NE
V p L/m2 Volume of peripheral compartment 22.9 21.9 (15.7–46.1) NE NE
Q L/h·m2 Intercompartmental clearance 13.1 13.3 (10.0–19.6) NE NE
Pharmacodynamic parameters for platelet       
k tr,P h−1 Rate constant of inter-compartmental platelet movement 0.0244 0.0246 (0.0236–0.0254) NE NE
SLOPE P Drug effect on platelet count 0.0656 0.0676 (0.0539–0.0930) 25.7 20.8 (1.30–56.0)
BASE P /mm3 Baseline platelet count 49,200 53,700 (36,100–95,800) 105 78.3 (38.3–110)
GAMMA P Shape factor for platelet count fluctuation 0.304 0.299 (0.264–0.325) NE NE
IMP   Maximum degree of platelet count recovery expected 55000 58700 (24200 – 98300) 78.3 72.9 (19.5 – 150)
IMK   Rate constant for asymptotic platelet count recovery 0.000530 0.000513 (0.000213–0.000691) NE NE
Pharmacodynamic parameters for neutrophil       
k tr,N h−1 Rate constant of inter-compartmental neutrophil movement 0.0132 0.0133 (0.0120–0.0139) NE NE
SLOPE N Drug effect on neutrophil count 0.263 0.237 (0.114–0.363) 57.5 58.1 (25.8–119)
BASE N /mm3 Baseline neutrophil count 3240 3015 (2110–4140) 43.5 40.6 (27.2–57.6)
GAMMA N Shape factor for neutrophil count fluctuation 0.193 0.181 (0.110–0.251) 39.4 36.7 (15.0–65.4)
Residual error       
σ PK 2 Variance of residual error (proportional) for PK 0.441 0.436 (0.354–0.505)
σ PD,P 2   Variance of residual error (additive) for platelet count 25,000 24,300 (18,800–29,600)
σ PD,N 2   Variance of residual error (additive) for neutrophil count 754 748 (613–839)
  1. Proportion of successful convergence: 78.8 % for PK model, 78.0 % for PD model
  2. NE not estimated