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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.