Population PK parameters for the final model and bootstrap resultsa

ParameterValue(s) for final model parameters
Final runBootstrap (n = 500 runs)
Median estimate90% CI
CL/F (liters/h)2.962.962.87–3.05
V2/F (liters)915913879–956
Q/F (liters/h)–5.43
V3/F (liters)664665634–692
Absorption lag time (h)0.9080.9300.904–0.950
Ka (h−1)0.2520.2540.226–0.296
Capsule effect on Ka0.9240.9140.805–1.03
Relative bioavailability (capsule)0.8630.8660.833–0.900
V2/F ratio (healthy volunteers/patients)1.351.351.30–1.41
V3/F ratio (healthy volunteers/patients)0.3470.3400.295–0.396
IIV CL/F32.132.030.0–34.1
IIV V2/F34.434.331.8–37.1
IIV CL-V2 block33.329.927.7–32.5
IIV Ka40.439.631.7–48.0
IIV ALAG144.343.438.8–56.1
IIV error33.033.227.2–38.5
Random residual variability (% CV)15.014.914.3–15.8
  • a Ka, absorption rate constant; CL/F, oral clearance from the central compartment; V2/F, volume of distribution for the central compartment; V3/F, volume of distribution for the peripheral compartment; Q/F, intercompartmental clearance; IIV, interindividual variability, expressed as the percent coefficient of variation; CI, confidence interval. The tablet formulation was considered the reference, i.e., F1tablet = 1.