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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