TABLE 2

Pharmacokinetic parameter estimates of the structural and final modelsb

ParameterStructural modelFinal model
Value (% RSE)95% CIValue (% RSE)95% CI
Typical value
    CL (liters/h)1.08 (3.9)0.99–1.16
    CL70 kg × (TBW/70)θ1 (liters/h)
        CL70 kg0.996 (4.2)0.91–1.09
        θ10.322 (22.6)0.169–0.496
    V1 (liters)18.9 (4.7)17.2–20.6
    V1, 70 kg × (TBW/70)θ2 (liters)
        V1, 70 kg16.6 (2.8)15.6–17.6
        θ20.631 (15.6)0.386–0.834
    V2 = V3 (liters)Equal to V1Equal to V1, 70 kg
    Q1 (liters/h)0.153 (6.2)0.133–0.1730.153 (6.4)0.13–0.18
    Q2 (liters/h)15.7 (6.1)13.7–17.714.1 (7.0)12.2–16.0
Interindividual variabilitya (%)
    CL15.4 (34.7)8.4–20.212.5 (50.3)4.5–17.7
    V21.1 (28.6)14.2–26.410.0 (39)5.5–14.2
Residual error (%)
    σadd study 112.6 (20.8)9.4–15.111.0 (16.5)9.0–13.1
    σadd study 24.4 (18.4)3.3–5.34.4 (19.3)3.2–5.5
    σadd study 38.4 (10.3)7.4–9.38.7 (14)7.1–10.0
OFV−931−975
  • a  Calculated by (eω21), where ω2 represents the variance.

  • b The eta and epsilon shrinkages of the interindividual variability for CL and V, and all three residual errors were all below 10%. Abbreviations: CL, clearance; CL70 kg, CL standardized to that for a typical 70-kg individual; V1, volume of distribution of the central compartment; V2 and V3, volumes of distribution of peripheral compartments; V1, 70 kg, volume of distribution of the central compartment standardized to that for a typical 70-kg individual; Q1, intercompartmental clearance between V1 and V2; Q2, intercompartmental clearance between V1 and V3; σadd, additive error on log scale; RSE, relative standard error based on the covariance step in NONMEM; 95% CI, 95% confidence interval obtained from nonparametric bootstrap analysis (n = 1,000); OFV, objective function value.