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Table 4 Final estimates of population PK-PD parameters

From: Saturable human neopterin response to interferon-α assessed by a pharmacokinetic-pharmacodynamic model

Parameter

Description

Estimate

%RSE

Bootstrap median (95% CI)a

Pharmacokinetics

CL/F (L/h)

Apparent clearance

12.2

7.39

12.5 (4.9~14.9)

V/F (L)

Apparent volume of distribution

691

6.54

712 (324~980)

D2 (h)

Duration of zero-order absorption

20.2

7.08

19.9 (16.6~23.0)

KA (h-1)

Absorption rate constant of first-order absorption

0.00653

16.23

0.00721 (0.0010~0.1715)

ALAG (h)

Lag time to the initiation of first-order absorption

85.7

3.92

88.1 (80.9~108.0)

RFb

Alternate variable for relative fraction absorbed in zero-order absorption process

0.185

55.68

0.24 (-1.17~0.94)

ωCL (%)

Between subject variability of CL

26.1

35.1

24.5 (14.4~32.7)

ωV (%)

Between subject variability of V

23.8

58.0

23.7 (0.4~37.6)

ωD2 (%)

Between subject variability of D2

35.7

27.1

34.8 (23.0~49.4)

ωRF (%)

Between subject variability of RF

34.7

64.1

32.1 (0.3~54.2)

ωka (%)

Between subject variability of KA

77.0

37.1

59.5 (0.7~95.4)

σadd (pg/mL)

Additive error

3.92

12.65

3.83 (-3.36~4.80)

σprop (%)

Proportional error

7.8

26.06

7.0 (-8.8~11.9)

Pharmacodynamics

BASE (nmol/L)

Baseline of neopterin

5.85

4.17

5.88 (5.39~6.34)

KOUT (h-1)

First-order elimination rate of serum neopterin

0.0311

17.20

0.03 (0.02~0.04)

EMAX

Maximum stimulatory effect

16.1

53.19

17.45 (7.06~62.42)

GA

Hill coefficient (γ)

1.24

11.85

1.27 (1.01~2.52)

CAc

Coefficient

405

115.80

616.5 (27~13115)

CBc

Coefficient

0.0068

27.73

0.0064 (0.0014~0.0119)

ECBc

Baseline of EC50

2.17

152.07

1.66 (0.05~74.67)

MTT (h)

Mean transit time

14.6

11.37

14.5 (9.82~19.2)

ωBASE (%)

Between subject variability of BASE

13.85

51.84

12.63 (3.91~20.79)

ωCB (%)

Between subject variability of CB

57.31

43.31

46.21 (0.32~72.61)

ωGA (%)

Between subject variability of GA

13.51

55.80

13 (0.32~36.49)

ωECB (%)

Between subject variability of ECB

21.31

172.97

21.39 (0.45~55.86)

ωMTT (%)

Between subject variability of MTT

13.36

94.92

10.75 (0.55~24.21)

σadd (nmol/L)

Additive error

1.14

11.05

1.11 (0.95~1.37)

  1. a95% CIs obtained from estimation of 1000 bootstrap-resampled datasets; bFraction absorbed in zero-order absorption, Fz = eRF/(1+ eRF); Fraction absorbed in first-order absorption: 1-Fz; cEC50 =ECB*(1+CA*(1-e-CB*Time)); RSE Relative standard error.